Aiming at the sticking phenomenon between the valve core and the valve sleeve when the valve core moves, and to solve the problem that the torque required to drive the valve core to rotate is large, the fluid–solid coupling simulation analysis of the valve core is carried out in this study, and then the valve core structure of the valve core is improved and its parameters are optimized based on the bird colony algorithm. The combination structure of the valve sleeve and valve core is studied, and the fluid–solid coupling model is established by Ansys WorkBench, and the static structure simulation analysis of valve sleeve and valve core before and after structural improvement and parameter optimization is performed. The mathematical models of triangular buffer tank, U-shaped buffer tank and combined buffer tank are established, and the structural parameters of the combined buffer tank are optimized by bird swarm optimization. The results demonstrate the triangular buffer tank has good depressurization effect but great impact, the pressure of the U-shaped buffer tank is stable and gentle but the depressurization effect is not ideal, while the combined buffer tank has obvious depressurization effect and good stability. At the same time, the optimal structural parameters of the combined buffer tank are cut-in angle of 72, plane angle of 60 and depth of 1.65 mm. The excellent structure and parameters of the combined buffer groove are obtained, so that the pressure buffer of the regulating valve at the key position of the valve port achieves the best effect, and an effective solution is provided for solving the sticking problem of the valve core of the regulating valve when working. The regulator controls the fluid and drives the load by changing the opening of the valve port. Its regulating ability is of great significance to the safe and efficient operation of the hydraulic system3. Spool and valve sleeve this is extremely important to the structure of the working pair and the parameters of the control valve working ability. Luo Yuxuan et al.4 analyzed and summarized the causes of the stock spool in valve engineering applications. The reasons for the spool stuck are divided into: mechanical reasons caused by machining precision or assembly error; Hydraulic reasons caused by the unbalanced moment of fluid action on the spool; Thermal causes caused by viscous heating of fluid under high pressure conditions, and pollution causes caused by particle retention in valve fit clearance. Aiming at the stuck phenomenon of 2D electro-hydraulic proportional directional valve spool, Liu Guowen et al.5 systematically analyzed the radial clamping force of 2D spool with or without eccentricity. MATLAB software is used to calculate the relationship between 2D spool radial clamping force, eccentricity and angle between high and low pressure holes. Depending on the characteristics of 2D valve, the improvement measures of 2D electro-hydraulic proportional directional valve spool are put forward. The flow field on the valve core surface is simulated by CFD using Fluent software. The velocity vector and pressure distribution before and after the improvement is compared, and the correctness of the improved measures is verified. Pei Xiang et al.6 compared various clamping phenomena of rotary valve and slide valve spool. The radial unbalance force of the rotary valve is analyzed theoretically some concrete measures to reduce the clamping phenomenon of rotary valve is put forward. To provide some help for the design and application of a rotary valve in the future. Sun Zegang et al.8. Studied the influence of U-shaped and V-shaped throttling groove structures on the cavitation performance of the valve. By improving the throttling groove structure optimized by genetic algorithm, the anti-cavitation performance of the valve can be obviously improved. Li Weijia et al.9 studied the valve opening-flow characteristics of the slide valve with a single U-shaped, oblique U-shaped and V-shaped base throttling grooves under the condition of constant pressure difference, Using particle swarm optimization algorithm, the optimal size of the throttle slot is obtained, which meets the requirements of valve opening-flow characteristics under the condition of constant pressure difference. Cao Jia Hao et al.10 designed a new type of limiting structure with buffer groove, which weakened the structural rigidity and improved the damping dissipation of impact energy. Through ANSYS software, the parameter iterative optimization analysis of the original limit buffer structure is carried out to find a reasonable structure parameter combination. Then, the transient dynamic performance of the structure based on the time domain method is considered by LS-DYNA software, and the buffering effect of the traditional and new type limiting structures is compared. Wu Weidong et al.11 aiming at the problems of small flow adjustment range and slow response of the U-shaped throttling groove of a certain type of load sensitive valve, a Ω-shaped throttling groove was designed by analyzing the functional relationship between valve opening and flow area. Particle swarm optimization (PSO) algorithm is used to optimize its organizational parameters with flow gain as the goal. Zhang Zhandong et al.12 put forward a calculation method of adding a K-shaped throttle slot at the shoulder of radial flow hole of the main spool of the reversing valve, and obtaining the equivalent flow area of the K-shaped throttle slot, aiming at the situation that the valve port of the reversing valve of coal mine hydraulic support has a large flow area gradient, which can only realize the on–off control function, and the pressure build-up is sudden, which is easy to induce the pressure impact of the support oil supply system. The purpose of actively regulate and controlling that flow area gradient of the valve port can be realized. Zhang Liqiang et al.13 aimed at the problem of valve port pressure impact caused by excessive internal flow of a slide valve. After analysis the influence of throttle groove structure parameters on its flow characteristics. The genetic optimization algorithm is used to obtain the Parato solution set of the U-shaped throttling groove which meets the fast response characteristics of flow and the pressure impact performance. The optimization results are verified by selecting specific throttle groove structure parameters. Li Ping14 put forward an improved scheme of a new type of throttling tank (U–V combined tank), particle swarm optimization algorithm is used to optimize the structure of throttle groove, the optimal structural parameters are obtained. Under the same valve opening, the flow area of the new throttle groove is larger than that of the original value (U-shaped groove). When the multi-channel valve reaches the rated flow rate, the opening of the new valve decreases and the flow adjustment range increases. Yi Sheng et al.15 carried out simulation research on the opening-flow characteristics of six kinds of throttling slots: single U-shaped, oblique U-shaped, V-shaped, 2U-shaped, 3U-shaped and U + V-shaped; Using GUI module in MABLAT, the optimization design software of throttle slot based on particle swarm optimization is developed. Fang Guihua et al.16 studied the influence of different parameters on the steady-state hydrodynamic force of the U-shaped throttling groove, and thought that the height of the U-shaped throttling groove had greater impact than the width.At present, the micro small hydraulic control valve is used more and more widely in Chin. Researchers and manufacturers at home and abroad have done a great deal of explorations on its theory, structure and parametersThrough analysis, it can be known that under normal working conditions, the pressure impact in the regulating valve, especially at the key position of the valve port, is easy to occur, which leads to the deformation of the valve core, and then leads to the clamping phenomenon between the valve core and the valve sleeve when it moves. To solve this problem, In the concrete analysis, the structural model of the regulating valve is simplified first, Then a mathematical model is established to calculate and study it, The calculation and analysis results of triangular buffer tank and U-shaped buffer tank is obtained, Then, the combined buffer tank is proposed, and the parameters of the combined buffer tank are optimized by the bird colony algorithm. Thereby improving the original valve core structure. Finally, through the comparative analysis of the fluid–solid coupling simulation before and after the valve port structure optimization of the regulating valve. It is concluded that the combined buffer groove can reduce the compression deformation of the valve core.This paper describes a micro-control valve with adjustable flow rate. Its working mechanism belongs to the category of hydraulic rotary valve, and its structure is shown in Fig. Micro-flow regulating valve controls the outlet flow by adjusting the opening size through the rotation of motor valve core. As showed in Fig. As showed in Fig. The servo motor drives the shift lever to rotate, so that the shift fork block reciprocates in the arc groove at the bottom of the valve sleeve. The angle of the arc groove at the bottom of the valve sleeve is 90, so the maximum rotation angle of the valve core is 90, as showed in Fig. dp is the oil pressure differential of the valve port cavity of the regulating valve; dV is the oil volume differential of the valve port cavity of the regulating valve; βe is the elastic modulus of oil (MPa); V is the initial volume (m3) of oil in the orifice cavity of the regulating valve.Taking the sealed cavity formed by the valve core and the valve sleeve as the research object, the pressure change in the valve port cavity can be calculated by the following formula:ω is the speed of the regulating valve (°/s); θ is the rotor angle (°) of the regulating valve.Assuming that the initial volume of the valve port volume of the regulating valve is V, the pressure formula is derived according to Eq. , and theThe volume of oil in the valve port volume can be represented by The three-dimensional structure of triangular buffer groove can be regarded as a triangular vertebral body, and its plane principle is the relative movement of triangle and circle. Its size is controlled by two parameters: cutting angle Ф and plane angle α, as showed in Fig. The triangular buffer groove is set at the end of the valve port of the U-shaped groove of the valve core. Firstly, the rotary motion of the valve core is expanded into a plane motion, which is equivalent to the rotary angle of the valve core. After expansion, it can be seen as the downward displacement L of the U-shaped groove of the valve core. Then, the relative motion of the U-shaped groove of the valve core and the waist-shaped groove of the valve sleeve is expanded into a plane motion, which is simplified into a mathematical model. Then, the geometric model is established for analysis and solution, as showed in the Fig. If the cross section of a triangular pyramid is always an obtuse triangle, the relationship between the depth angle and the plane angle is as follows, and the relationship can be expressed as:P, yP), Q. Substitute two points P and Q. The PQ linear equation can be obtained as follows:Simultaneous solution Eqs. –7),can ,can 7),c∆ADC coincides with the working plane of the U-shaped valve port of the valve core, In the process of turning the waist groove of the valve sleeve into the triangular buffer groove, Where any cross section ∆PQM is an obtuse triangle, the area of ∆PQM is defined as the flow area of the triangular groove.As showed in Fig. For triangle whose cross section is kept obtuse, that relationship between depth angle and plane angle is as follows:∆PQM is solved.Then, a space rectangular coordinate system is established with point of A as the coordinate origin, and the over-current area PQ. Suppose the point of M, as can be seen from Fig. The equation can be obtained by substituting the point of N into the linear equation Cq is the flow coefficient; Is the inlet and outlet pressure difference of regulating valve (MPa); A is the throttling area of the valve port cavity; ρ is the density of hydraulic oil (kg/m3).As the regulating valve is a micro-hydraulic component, the volume change of the triangular buffer groove flowing into or out of the valve port cavity of the regulating valve can be obtained according to the flow formula of the throttle orifice:According to the above formula, When the volume of the triangular buffer groove flowing into or out of the valve port cavity changes into the operation of the regulating valve, The cavity of the valve port is surrounded by a valve sleeve and a valve core, and the volume of oil in the cavity is based on Eqs.  and 16)16). The In the formula, only the over-current area is a variable value, and the rest are fixed values, which can be set:β ϵ . Therefore, considering the pressure gradient curve results comprehensively, it can be obtained that the triangular buffer groove has the best depressurization effect at the valve port cavity of the regulating valve at the cutting angle Ф = 72° and plane angle β ϵ  .According to the above theoretical analysis, numerical simulation is carried out with MATLAB, and the curves of pressure gradient with time under different cutting angles and different plane angles under triangular buffer groove structure can be obtained by calculation, as showed in Fig. As for the U-shaped buffer tank, it can be seen as consisting of a semi-cylindrical section and an equal cross-sectional area section, The size of its structure can be determined by width b and depth h, The U-shaped buffer groove is arranged at the U-shaped valve port of the valve core. When the U-shaped groove is opened in the semi-cylindrical section, the flow area increases rapidly, and when it transits to the section with equal cross-sectional area, the flow area remains unchanged.As showed in Fig. As showing in Fig. These variables axis φ ∈ . It can be obtained through the calculation of the above formula: OB:Establish the rectangular coordinate system of the simplified model. Let the equation of semicircle O and the equation of semicircleS is mainly related to the length of KT, but it can be divided into three cases for the straight line KT, as showed in Fig. Among them, h is the groove depth of the U-shaped buffer groove. According to geometric analysis, the area L ∈ , as showed in Fig. K and T.When L ∈ , as showed in Fig. K intersect the circle, while the point T intersects the straight line.When L ∈ , as shown in Fig. K and T intersect with a straight line.When K and T; through simplifying model analysis, it can be concluded that the overflow area of the U-shaped buffer tank. The following formula is obtained:Simultaneous solution of the above equation can lead to point According to the same principle, for the pressure gradient of the valve port cavity, only the flow area is a variable value, and the rest is a fixed value. When the volume of the valve port sealed cavity flowing into or out of the U-shaped buffer groove changes, the valve port cavity is composed of a valve sleeve and a valve core structure, and the oil volume in the cavity can be deduced according to formulas , 18) an an18) anAccording to the above analysis, the mathematical model is written by MATLAB, and the pressure gradient curve of U-shaped buffer groove with the same depth and different cutting angles and the pressure gradient curve of U-shaped buffer groove with the same cutting angle and different depths can be obtained after calculation.h ∈ (1.5–1.7) should be selected. Therefore, comprehensive consideration of the pressure gradient curve results shows that when the cutting angle h ∈ (1.5–1.7), the U-shaped buffer groove has the best depressurization effect at the valve port of the regulating valve.As showed in Fig. 17. The algorithm is based on swarm intelligence evolved from the social behavior and social interaction of birds, and birds share information among groups through foraging behavior, alert behavior and flying behavior in their living habits19. Studying these social behaviors and interactions can effectively optimize the problem, and has the advantages of fast convergence and avoiding falling into local optimum21. Simplify the social behavior of birds into the following rules.In the process of alerting and foraging behavior of birds, each bird can arbitrarily change its alert behavior and foraging behavior;In the process of foraging, in order to get the best experience of finding food. Every bird can record and update individuals and groups.Birds try to move to the center of the group while keeping alert. Affected by the competition among birds, birds with high reserves are more likely to approach the center of the flock than those with low reserves.Birds randomly switch between production and search, and regularly fly to another location. The producer is the bird with the highest reserves, otherwise it grows up to be a requester. Other birds will randomly choose between the producer and the requester.In the process of bird looking for food, birds are randomly divided into requesters and producers, and the requesters will follow the producers to find food.Bird swarm optimization algorithm is a new biological heuristic optimization algorithm proposed by Xian-Bing Meng et al. 23 are stated: suppose there are n birds in the B-dimensional space. At the position at time T, individuals are searching for food in groups, that is, the position of the bird at time T can be expressed as Xi.Behaviors under each ruleForaging behavior: when each bird searches for food through its own different experience, it can write a mathematical way according to rule 2:The pressure change in the valve port cavity during the rotation of the control valve is studied. According to the pressure gradient equation of the sealed cavity under the combined pressure groove structure, the pressure in the valve port cavity changes. Therefore, in order to obtain the parameters of the combined pressure tank with better pressure reduction effect in the process of pressure reduction, the pressure in the valve port cavity of the regulating valve is simulated and calculated by using the bird swarm optimization algorithm with different cut-in angles and depth dimensions.25 of the bird swarm optimization algorithm as showed in Fig. Initialize the basic parameters of the bird swarm optimization algorithm, such as the total number of birds, the particle dimension of birds, the maximum number of iterations, the flying frequency of birds, the foraging probability and other parameters, and generate the population under various constraints.Ci). According to the objective function, the fitness value F(x) corresponding to the position of each bird is calculated, and the initial optimal fitness value F(x1)min and bestlndex are selected from the fitness values as the code corresponding to its optimal fitness value.Set the pressure gradient equation of the regulating valve in the depressurization process as the objective function, According to the position rand > pi, birds choose to perform foraging behavior in social behavior, and update according to the formula; if rand > pi, according to the bird type Eq. min. When the number of iterations i = 1 and glbol_best = F(xi)min; Compare the sizes of glbol_besti−1 and F(xi)min,glbol_besti = min{glbol_besti−1,F(xi)min}.Update the individual fitness value of the flock again, and compare it with the fitness value calculated at the previous moment, so as to update the optimal fitness value of the next generation flock i = i + 1 is executed, and the number of iterations i at this moment is compared with the maximum number of iterations tmax. If i < tmax jump back to step 3; otherwise, the optimization is finished.Judging whether the iteration meets the iteration termination condition. This paper aims at the pressure gradient model of the valve port volume of the regulating valve under the combined tank, and optimizes the parameters of the combined pressure tank according to the flow chart of the algorithm27. Because the triangular buffer groove and the U-shaped buffer groove are in an optimal range of depth and plane angle, and each has its own advantages, If the two grooves are combined, it is necessary to optimize the parameters. In this paper, the bird swarm algorithm will be used to optimize the parameters. The algorithm flow chart of the bird swarm optimization algorithm is shown in Fig. Generally, the iteration termination condition is that the iteration exceeds the iteration limit number and the algorithm operation ends, otherwise, the iteration continuesBecause both triangular buffer groove and U-shaped buffer groove have certain defects when working alone, we propose a combined buffer groove with triangular buffer groove at the front end of U-shaped buffer groove. The combined buffer groove is a complex combined structure, which needs to be divided into different stages to establish the mathematical model of the valve port cavity. The structures of two kinds of buffer grooves have been calculated before, and the valve port cavity model of the combined buffer groove is deduced based on the above. As showed in Fig. After entering the U-shaped buffer tank, the overflow area changes steadily, and the pressure impact gradually decreases. From the structural aspect, the combined buffer tank has more stable depressurization characteristics than triangular buffer tank and U-shaped buffer tank. The flow area under the combined buffer groove structure can be regarded as the waist groove of the valve sleeve which coincides with the triangular buffer groove and the U buffer groove in turn.Because the combined buffer groove is a combination of triangular buffer groove and U-shaped buffer groove, its area should be equal to that of both buffer grooves, so the length ratio of the two buffer grooves is 2:3. The area of both should account for 2/5 and 3/5 of the total area respectively. Through MATLAB algorithm calculation, the optimal cutting angle is 72 by comparing triangular buffer groove with U-shaped buffer groove. At this time, the optimal plane angle is between 45 and 63, while the optimal depth h of U-shaped buffer groove should be between 1.5 and 1.7 mm. According to the size proportion of triangular buffer tank and U-shaped buffer tank in the combined buffer tank, the formula of overflow area of the combined buffer tank can be obtained.According to formulas  and 39)39)49\doca1 and a2 to 1, and the social evolution coefficient to 1. The parameters of the combined pressure tank are optimized by using the bird swarm optimization algorithm. The objective function is simulated by MATLAB software, and the results are showed in Fig. The pressure gradient of the valve port cavity under the combined structure of valve sleeve and valve core is taken as the objective function, the plane angle and depth h are taken as constraint conditions, and the pressure gradient is taken as the objective function. Set the total number to 10, the spatial dimension to 1, the number of iterations to 100, the flight frequency to 8, the cognitive coefficient to 1, the parameters In order to get the optimal pressure gradient of the valve port volume under the combined structure of valve sleeve and valve core, the introduced fitness function is iterated, and the minimum value of the fitness function is iterated. As shown in Fig. 29. Through the fluid–solid coupling simulation comparison of the combination structures of the valve sleeve and the valve core of non-grooved, triangular buffer groove, U-shaped buffer groove and combined buffer groove, the advantages of the optimal combined buffer groove are analyzed and compared.The purpose of optimization is to reduce the stress concentration at the U-shaped notch of the combined structure of the valve sleeve and valve core while ensuring the normal operation of the regulating valve. Compared with the single-objective optimization of triangular buffer slot and U-shaped buffer slot, the multi-objective optimization of the bird swarm algorithm is more likely to obtain a better solution, and the influence of design variables on the objective function is clearerUnder the condition of ensuring the accuracy of numerical calculation, taking into account the complex curved surface structure of the regulating valve, unstructured tetrahedral grids are adopted for the regulating valve.hen, according to the grid independence test, the number of grids generated by fluid in the valve sleeve and valve core combination structure is 1.18 million, which can fully guarantee the accuracy of numerical calculation results and set the expansion layer for the liquid in the valve body, as showed in Fig. 31. The ALE method is used to deal with the fluid–solid coupling of valve sleeve and valve core combination structure. In “Reference Frame”, the solid is set as Lagrangian and the liquid is set as Eulerian. The geometric model and grid of the valve body and the fluid can overlap, and the related parameters of the regulating valve are shown in Table The properties of the fluid material are shown in Table 33. Through the results of static analysis below, the internal structure of the control valve is further optimized and improved.Static structural (ANSYS) is used to analyze the combined structure of the valve core and valve sleeveCarry out static simulation analysis on the valve core and valve sleeve inside the regulating valve, and get the corresponding total deformation cloud map, as showed in Figs. Through the deformation diagram obtained by fluid–solid coupling simulation under the structure of non-grooved, triangular buffer groove, U-shaped buffer groove and combined buffer groove, it can be seen that the buffer groove structure on the valve port of the valve core can reduce the stress concentration caused by pressure impact. According to Fig. Mathematical models of valve sleeve and valve core of triangular and U-shaped buffer grooves are established respectively, and the pressure gradient curves of them are obtained through MATLAB simulation calculation. Through analysis, it is concluded that if the optimal triangular buffer groove and the optimal structural parameters of U-shaped buffer groove are to be taken simultaneously, the cutting angle should be 72, the plane angle should be in the range of 45–72 and the depth should be 1.5–1.7 mm, and the pressure reduction effect can be obtained at this time.By studying the structure of triangular buffer and U-shaped buffer groove, a combined buffer groove structure is designed to combine the advantages of both. Therefore, taking depth angle and depth as constraints, the pressure gradient of the valve port cavity under the combined buffer groove structure is taken as the objective function. Through the bird swarm optimization algorithm (BSA), it is found that the pressure reduction effect of the combined buffer tank is the best when the plane angle is 60 and the depth is 1.65 mm. At this time, the structural parameters are the optimal values of the depth angle and depth of the combined buffer tank.Through the fluid–solid coupling analysis of the combined structure of valve sleeve and valve core before and after optimization, it is concluded that opening buffer groove can effectively improve the deformation of valve core and compared with U-shaped buffer groove and triangular buffer groove, the combined buffer groove can effectively improve the deformation of the combined structure of valve sleeve and valve core.Aiming at the phenomenon that the valve core of the micro-flow regulating valve is deformed due to pressure impact, and the valve sleeve is stuck in motion, and to solve the problem that the torque required to drive the valve core to rotate is large, a buffer groove is opened at the valve port of the valve core. In this paper, the structure of buffer tank is optimized, and its parameters are optimized and the improved structure is compared by fluid–solid coupling simulation. The conclusions are as follows.Therefore, the excellent structure and parameters of the combined buffer tank are obtained, and the pressure impact of the regulating valve at the key position of the valve port is reduced to the best effect, which provides an effective solution for solving the problem of the locking of the regulating valve when working.


Passalidae) are a subsocial family of Coleoptera with approximately 1000 known species of saproxylophagous diet and pantropical distribution, with few extratropical species. Because of their high levels of endemism , feeding habits, and complex subsociability; Passalidae is considered an excellent biological subject for taxonomic, biogeographical, and evolutionary studies. Colombia is the richest country with more than 118 recorded species of Passalidae, most of the species being related to humid and mountain areas. Colombia’s Caribbean region constitutes the northern portion of the country, extending for more than 130,000 km2 and includes four of the eight biogeographical provinces of Colombia. Since the 2000s this region has been the subject of systematic surveys for Passalidae; as a result, 18 passalid species have been recorded to date. After new explorations and review of entomological collections, the knowledge of the passalid fauna for the region is updated, recording 28 species  for which are provided species diagnoses, photographs, and a taxonomic key. The dry plain, characteristic of the lowlands, is dominated by widely distributed species such as Passaluspunctiger and Passalusinterstitialis, while the mountainous systems provide species of more restricted distributions, some of them endemic to the Colombian Caribbean.Bess beetles ( Passalidae are saproxylophagous diet, playing an important role in nutrient recycling , given the high levels of endemism typified by montane passalid species , covering more than 130,000 kmbia Fig. .Passalidae in the Colombian Caribbean region, providing diagnoses, a taxonomic key, and the description of new species. A refined database of the revised material is also provided, with the aim of promoting the study of the family, facilitating the identification of species and the recognition of areas with exploration gaps.The Caribbean region of Colombia is the most comprehensively know for passalids, based in amount of works published in the last two decades e.g., . Jiménezhttps://www.gbif.org/dataset/54F7AF87-E0A3-4816-AE9F-ED77C45F2455). We also included 380 records from Museo de Zoología de la Universidad de Sucre, Colombia (GBIF dataset https://www.gbif.org/dataset/6F1BED71-743E-407B-8862-E7E2E1CED896), and conducted a literature review. The total records, including those from literature, are included in a Darwin core formatted file  and validated in GBIF Data Validator and the geographic validation service in QGIS provided by SiB Colombia (https://biodiversidad.co/formacion/laboratorios/QGIS). Taxonomic validation was performed according to the GBIF taxonomic tree.We studied and digitized 5400 specimens deposited in Colección Entomológica Universidad del Magdalena (CBUMAG-ENT), Colombia , Rhodocanthopus (2 spp), Spasalus (2 spp), Paxilus (1 spp), Veturius (4 spp), Popilius (3 spp), Heliscus (1 spp), Odontotaenius (1 spp), and Verres (2 spp) EE542A41-29DD-5D06-ADF4-3FC452E87F5441.2–52.7 mm total length. Body robust. Anterior border of the frons with two prominent secondary mediofrontal tubercles. Mediofrontal tubercles small, located on base of each laterofrontal tubercle. Central tubercle with apex slightly free. Lateroposterior tubercles distinct. Eyes large. Antennal club tri-lamellate, with lamellae long. Lacinia with apex bidentate. Mediobasal area of mentum protruding and glabrous. Marginal pronotal groove occupying 2/3 of the pronotum anterior border. Prosternellum rhomboidal, acute. Mesosternum with some sparse setae, with inconspicuous and elongated scars. Metasternum pubescent anterolaterally and in lateral groove; disc smooth and delimited by punctations posteriorly to middle. Humeri pubescent, epipleura pubescent in basal 2/3. Last abdominal sternite with incomplete marginal groove. Anterior ventral border of the profemur with conspicuous groove. Mesotibia with one or two small spines, metatibia unarmed.P.punctiger, but is distinguished by its larger size and incomplete marginal groove in last abdominal sternite (complete in P.punctiger).Distributed from Panama to Argentina and Trinidad and Tobago . This spTaxon classificationAnimaliaColeopteraPassalidae3.Eschscholtz, 1829E7663B3E-23B6-547C-A4B5-F9815E1BC44623.6–29.9 mm total length. Body flattened. Anterior border of the frons with two prominent secondary mediofrontal tubercles. Mediofrontal tubercles large, located on base of each laterofrontal tubercle. Central tubercle with apex not free. Lateroposterior tubercles distinct. Eyes large. Antennal club tetra-lamellate, fourth lamella reduced. Lacinia with apex bidentate. Mediobasal area of mentum glabrous and slightly protruding. Marginal pronotal groove occupying 2/3 of the pronotum anterior border. Prosternellum rhomboidal, truncate. Mesosternum glabrous, with distinct elongated scars. Metasternum pubescent anterolaterally and in lateral groove; disc smooth and delimited posteriorly to middle by punctations. Humeri pubescent, epipleura pubescent in basal third. Last abdominal sternite with complete marginal groove. Anterior ventral border of the profemur with distinct groove. Mesotibia lacking spine or with single small spine.P.punctiger, P.interstitialis differs by its smaller size, flattened body, and apex of central tubercle not free.Distributed from Mexico to Argentina  and CubaTaxon classificationAnimaliaColeopteraPassalidae4.Lepeletier & Serville, 18250F19E65E-23DE-5756-9734-2B7B096FF29B28.4–41.7 mm total length. Body robust. Anterior border of the frons with two prominent secondary mediofrontal tubercles. Mediofrontal tubercles large, located on base of each laterofrontal tubercle. Central tubercle with apex slightly free. Lateroposterior tubercles conspicuous. Eyes large. Antennal club tri-lamellate, with lamellae long. Lacinia with apex bidentate. Mediobasal area of mentum protruding and glabrous. Marginal pronotal groove occupying 2/3 of the pronotum anterior border. Prosternellum rhomboidal, truncate. Mesosternum glabrous, with conspicuous and elongate scars. Metasternum pubescent anterolaterally and in lateral groove; disc smooth and delimited posteriorly to middle by punctations. Humeri pubescent, epipleura pubescent in basal 2/3. Last abdominal sternite with complete marginal groove. Anterior ventral border of the profemur with distinct groove. Meso- and metatibia with one or two small spines.Distributed from Mexico to Argentina. This the most common species for the lowlands of the Colombian Caribbean.Taxon classificationAnimaliaColeopteraPassalidae5.Jiménez-Ferbans, Reyes-Castillo & Amat-García, 201402CB403D-DC47-533F-AC0A-390E9F4846A328.7–34.2 mm total length. Body slightly flattened. Anterior border of frons with two prominent secondary mediofrontal tubercles, almost completely fused. Mediofrontal and laterofrontal fused, large. Central tubercle with apex very free, reaching or surpassing anterior frons border. Lateroposterior tubercles small, distinct. Eyes large. Antennal club tri-lamellate, with lamellae long. Lacinia with apex bidentate. Mediobasal area of mentum protruding and pubescent. Marginal pronotal groove occupying 2/3 of the pronotum anterior border. Prosternellum rhomboidal, truncate. Mesosternum glabrous, with distinct and elongate scars. Metasternum pubescent anterolaterally, lateral groove glabrous; disc smooth and delimited by punctations excluding the anterior part. Humeri pubescent, epipleura with some setae basally. Last abdominal sternite with complete marginal groove. Anterior ventral border of the profemur with conspicuous groove. Meso- and metatibia with small spines or unarmed.SNSM, this species seems to be endemic to this biogeographical province.Described from Taxon classificationAnimaliaColeopteraPassalidae6.Jiménez-Ferbanssp. nov.5CB4C5F6-23B1-5869-9551-E4D2D5167CDDhttps://zoobank.org/DD10DD35-3D8D-4D4C-A162-EA5DCA40DC58Holotype Colombia • ♂; La Guajira, Serranía del Perijá, Cerro Pintao; 10°25'37.9"N, 72°56'33.3"W; 3019 m alt.; 08 Aug 2015; L. Granados leg.; CBUMAG: ENT: 20605.Hemibrachypterous. Frons wide, anterior frontal edge straight, without middle indentation or secondary mediofrontal tubercles. Central tubercle wide at the base, without a sulcus in the posterior part, apex free, almost reaching the anterior frons border. Medial basal mentum impunctate and glabrous. Prosternellum rhomboidal and opaque in the area between procoxae, without longitudinal groove. Anterolateral part of metasternum and lateral fossa pubescent, pubescence reaching the posterior region of the lateral fossa. Metasternal disc without punctures, delimited by numerous punctures posteriorly. Humeri pubescent and epipleura glabrous.Habitus Fig. : total lHead . Central tubercle wide at the base, with a sulcus in the posterior part, apex free, reaching the anterior frons border. Medial basal mentum with punctures and setae on the posterior border. Prosternellum rhomboidal and opaque in the area between procoxae, with a deep longitudinal groove. Anterolateral part of metasternum with scarce pubescence, lateral fossa glabrous. Metasternal disc without punctures, delimited by numerous punctures medially and posteriorly. Humeri with scarce pubescence basally, epipleura glabrous.Habitus Fig. : total lHead 9B16DF7E-A0F9-527C-9F80-81D63AB44C4A16.3–19.8 mm total length. Body subcylindrical. Anterior border of the frons with strong middle indentation, without secondary mediofrontal tubercles. Mediofrontal and laterofrontal fused, large. Central tubercle with apex not free. Lateroposterior tubercles conspicuous and conical. Eyes reduced. Antennal club tri-lamellate, lamellae short. Lacinia with apex bidentate. Mediobasal area of mentum protruding and glabrous. Marginal groove widened, occupying 2/3 of the anterior margin of the pronotum. Prosternellum rhomboidal, acute. Mesosternum glabrous; mesosternal scars oval and distinct. Metasternum glabrous anterolaterally and in lateral groove; disc smooth and delimited by punctations posteriorly to laterally. Humeri and epipleura glabrous. Anterior ventral border of the profemur with conspicuous groove. Meso- and metatibiae with strong spines.R.maillei, from which it differs by its larger size, reduce punctation on the pronotum, which do not reach the mid zone and the metasternal disc not abundantly punctate.Species very similar to Taxon classificationAnimaliaColeopteraPassalidae15.3BDEE053-E734-53D8-BECF-DCC3D809C8A414.0–16.5 mm total length. Body flattened. Anterior border of frons with strong middle indentation, on the sides of which are two insinuated tubercles. Mediofrontal and laterofrontal fused, large. Central tubercle with apex not free. Lateroposterior tubercles distinct and transverse. Eyes reduced. Antennal club tri-lamellate, lamellae short. Lacinia with apex bidentate. Mediobasal area of mentum protruding and glabrous. Marginal groove widened, occupying 1/2 of the anterior margin of the pronotum. Prosternellum rhomboidal, truncate. Mesosternum glabrous; mesosternal scars elongated and conspicuous. Metasternum glabrous anterolaterally and in lateral groove; disc smooth and delimited by punctations posteriorly to laterally. Humeri glabrous; epipleura with scattered setae in basal area. Anterior ventral border of the profemur with conspicuous groove. Meso- and metatibiae with strong spines.Described from the Chocó department of Colombia , this spTaxon classificationAnimaliaColeopteraPassalidae16.72C7D368-F6FB-544E-A86B-E0D325E4BA7217.6–18.2 mm total length. Body robust. Mediofrontal and laterofrontal fused, large. Central tubercle with apex not free. Eyes large. Antennal with five lamellae. Lacinia with apex unidentate. Mediobasal area of mentum protruding, with setae along almost its entire extension. Marginal groove widened, occupying 2/3 of the anterior margin of the pronotum. Anterior border of mentum almost straight. Prosternellum rhomboidal. Anterior ventral border of the profemur with conspicuous groove.Distributed widely in South America, this species has been recorded also in Lesser Antilles and Puerto Rico .Taxon classificationAnimaliaColeopteraPassalidae17.Amat-García & Fonseca, 1998AF01CC46-086E-5C0E-9B24-FBA12D2792B115.75–16.30 mm total length. Body robust. Mediofrontal and laterofrontal fused, large. Central tubercle with apex not free. Eyes large. Antennal with five lamellae. Lacinia with apex unidentate. Mediobasal area of mentum protruding, without setae in the posterior border. Marginal groove widened, occupying 2/3 of the anterior margin of the pronotum. Anterior border of mentum almost straight. Prosternellum rhomboidal. Anterior ventral border of the profemur with conspicuous groove.S.crenatus and S.paulinae are subtle, they may be synonymous.Comments. Known only from material type from Sierra Nevada de Santa Marta. The differences between The species of this tribe are recognized by having a frontoclypeus, below which the clypeus is hidden .Taxon classificationAnimaliaColeopteraPassalidae18.9EB41432-C97C-5246-AA2B-1D9CABC9EBC928.7–32.5 mm total length. Anterior border of the labrum straight or slightly concave. Frontoclypeus straight, not swollen in the middle. Frontal-clypeal suture present and strong. Internal tubercles conspicuous, joined to central tubercle by Y-shaped ridges. Central tubercle small, with apex not free; lateroposterior tubercles distinct and transverse, with a superior groove extending over the total length of the tubercles. Frontal fossae pubescent posteriorly. Postfrontal groove complete, slightly erased in the middle. Mediobasal area of the mentum glabrous. Marginal groove over anterior border of the pronotum not expanded. Mesosternum glabrous. Metasternum pubescent anterolaterally and in lateral groove; disc not delimited by punctations. Mesotibiae and metatibiae with a small spine or unarmed. Humeri and epipleura glabrous; anterior vertical face of elytra pubescent.Taxon classificationAnimaliaColeopteraPassalidae19.5716BA15-245B-5D6D-BF82-90A35D624F1628.8 mm total length. Anterior border of the labrum straight or slightly concave. Frontoclypeus swollen in the middle. Frontal-clypeal suture present and strong. Internal tubercles small, not joined to the central tubercle. Central tubercle large, with apex free; lateroposterior tubercles absent. Frontal fossae glabrous. Postfrontal groove complete. Mediobasal area of mentum glabrous. Marginal groove over anterior border of pronotum not expanded. Mesosternum glabrous. Metasternum with scarce pubescence anterolaterally and in lateral groove; disc delimited by punctations posteriorly. Mesotibiae and metatibiae with a small spine. Humeri and epipleura glabrous; anterior vertical face of elytra pubescent.Taxon classificationAnimaliaColeopteraPassalidae20.Reyes-Castillo & Castillo, 199294756784-8527-5040-AEE5-A9B9C423C47323.1–25.0 mm total length. Anterior border of the labrum slightly concave. Frontoclypeus straight or slightly concave. Frontal-clypeal suture present and strong. Internal tubercles conspicuous, joined to central tubercle by Y-shaped ridges. Central tubercle small, with apex not free and posterior to level of lateroposterior tubercles which are conspicuous and transverse. Frontal fossae pubescent. Postfrontal groove complete. Mediobasal area of the mentum glabrous. Marginal groove over anterior border of the pronotum slightly expanded. Mesosternum glabrous. Metasternum with scarce pubescence anterolaterally and in lateral groove; disc not delimited by punctations. Meso- and metatibiae with small spines. Humeri with scarce setae; epipleura glabrous; anterior vertical face of elytra pubescent.Popiliuserotylus was described from Panama. The specimens studied here show some setal variation in comparison with the type material; they could be a new species very closely related to P.erotylus.Taxon classificationAnimaliaColeopteraPassalidae21.915F3209-943B-5366-8EE7-2CA9A2962ACD21.4–23.5 mm total length. Anterior border of the labrum slightly concave. Frontoclypeus straight or slightly expanded forward. Frontal-clypeal suture present and strong. Internal tubercles small, joined to central tubercle by Y-shaped ridges. Central tubercle small, with apex not free and almost even with lateroposterior tubercles which are distinct and transverse. Frontal fossae pubescent. Postfrontal groove complete. Mediobasal area of the mentum glabrous. Marginal groove over anterior border of the pronotum not expanded. Mesosternum glabrous. Metasternum pubescent anterolaterally and in lateral groove, pubescence extending beyond lateral groove; disc not delimited by punctations. Meso- and metatibiae with a small spine. Humeri and epipleura glabrous or with scarce setae basally; anterior vertical face of elytra pubescent.Common species from the north of the Eastern Cordillera (Serranía del Perijá and Sierra de Venezuela) . It is fTaxon classificationAnimaliaColeopteraPassalidae22.CE7B01B0-6969-5ADE-928C-D1E6C2E2570F20.6–24.4 mm total length. Anterior border of the labrum slightly concave. Frontoclypeus straight or slightly concave. Frontal-clypeal suture present and strong. Internal tubercles conspicuous, joined to central tubercle by Y-shaped ridges. Central tubercle small, with apex not free and even with lateroposterior tubercles which are conspicuous and transverse. Frontal fossae glabrous or rarely pubescent. Postfrontal groove complete. Mediobasal area of the mentum glabrous. Marginal groove over anterior border of the pronotum slightly expanded. Mesosternum glabrous. Metasternum with scarce pubescence anterolaterally and in lateral groove; disc not delimited by punctations. Meso- and metatibiae with small spines. Humeri with scarce setae; epipleura glabrous; anterior vertical face of elytra pubescent.P.marginatus has been recorded from Argentina, Bolivia, Brazil, Colombia, French Guiana, Peru and Suriname , in which there were also colonies of Leptogenys sp. (Formicidae). Veturiusimpressus is the only Proculini endemic to the Caribbean region of Colombia.This species seems to be common in the middle elevations of Sierra Nevada de Santa Marta. It has been collected in both forest areas and in shady coffee plantations; in the latter within logs of Taxon classificationAnimaliaColeopteraPassalidae27.Kuwert, 18984BADAAC1-F0B1-5398-90C0-58555D9A877F47.5–50.4 mm total length. Anterior border of the labrum straight or slightly concave. Frontoclypeus almost straight. Frontal-clypeal suture absent. Internal tubercles small, joined to central tubercle by V-shaped ridges. Central tubercle small, with apex slightly free, upward projected; lateroposterior tubercles large, conspicuous, and transverse. Frontal fossae glabrous. Postfrontal groove complete. Mediobasal area of the mentum pubescent. Marginal groove over anterior border of the pronotum expanded. Mesosternum glabrous. Metasternum pubescent anterolaterally and in lateral groove; disc not delimited by punctations. Meso- and metatibiae unarmed. Humeri and epipleura glabrous; anterior vertical face of elytra pubescent.Taxon classificationAnimaliaColeopteraPassalidae28.Kuwert, 18917E0C231C-2EF2-5E98-A354-AC70EDEDD13B41.4–46.5 mm total length. Anterior border of the labrum straight or slightly concave. Frontoclypeus almost straight. Frontal-clypeal suture absent. Internal tubercles small, joined to central tubercle by V-shaped ridges. Central tubercle small, with apex not free; lateroposterior tubercles large, distinct, and transverse. Frontal fossae with some setae. Postfrontal groove complete. Mediobasal area of the mentum glabrous. Marginal groove over anterior border of the pronotum expanded. Mesosternum glabrous. Metasternum pubescent anterolaterally and in lateral groove; disc not delimited by punctations. Meso- and metatibiae with a small spine. Humeri and epipleura glabrous; anterior vertical face of elytra pubescent.Originally described from Venezuela, this species is distributed in the Andes of Bolivia, Colombia, Ecuador, Peru, and Venezuela .Passalus (Mitrorhinus) arrowi Hincks, 1934 labeled as “Sierra Nevada de Santa Marta, San Pedro de la Sierra, 1530 m., 20 abr 1992, G. Amat leg. ”. However, as P.arrow for the Sierra Nevada de Santa Marta must be rejected. monopolizes the elements endemic to the Caribbean region of Colombia, all of them distributed between 1500 and 2100 masl. Of the 14 species recorded in the SNSM, four are exclusive to this region , which highlights the biogeographic importance of this mountain massif. For its part, the Perijá mountain range represents another site with a significantly high richness of Passalidae in the Caribbean (10 species), most of them represented in medium elevations (1500 m), representing Andean elements. Perijá mountain range belongs to the Norandina province and harbors one species endemic to Colombia .With 28 species, the Colombian Caribbean hosts an important richness of passalid species, which also exhibits a unique composition. The dry plain, characteristic of the lowlands of northern Colombia, is dominated by widely distributed species such as Passalidae. It is in this province where species shared between the Colombian Pacific and Mesoamerica are also recorded . Likewise, according to Passalidae in Colombia, accounting for 34 species (14 of which are endemic). Presumably, ecological and historical factors make the Chocó-Magdalena province a rich area for Passalidae, since this is the most humid area for Colombia , Córdoba has the highest richness is Córdoba (15 species), due to the high richness recorded in the southern portion of the department, which biogeographically belongs to the Chocó-Magdalena province . The sec


There are various 1,2-cis glycosides in nature, such as α-glucoside and β-mannoside in glycoproteins, glycolipids, proteoglycans, microbial polysaccharides, and bioactive natural products. In the structure of polysaccharides such as α-glucan, 1,2-cis α-glucosides were found to be the major linkage between the glucopyranosides. Various regioisomeric linkages, 1→3, 1→4, and 1→6 for the backbone structure, and 1→2/3/4/6 for branching in the polysaccharide as well as in the oligosaccharides were identified. To achieve highly stereoselective 1,2-cis glycosylation, including α-glucosylation, a number of strategies using inter- and intra-molecular methodologies have been explored. Recently, Zn salt-mediated cis glycosylation has been developed and applied to the synthesis of various 1,2-cis linkages, such as α-glucoside and β-mannoside, via the 1,2-cis glycosylation pathway and β-galactoside 1,4/6-cis induction. Furthermore, the synthesis of various structures of α-glucans has been achieved using the recent progressive stereoselective 1,2-cis glycosylation reactions. In this review, recent advances in stereoselective 1,2-cis glycosylation, particularly focused on α-glucosylation, and their applications in the construction of linear and branched α-glucans are summarized.Controlling the stereoselectivity of 1,2- O-naphtO-benzylidene-2-O-(o-TAB)-D-glucopyranoside (19) with 4,6-O-naphthylidene-3-O-triisopropylsilyl-2-O-(o-TAB)-D-glucopyranosyl trichloroacetimidate (1f*) under α-directing conditions and subsequent deprotection of the TIPS group to liberate the 3-hydroxy group afforded the tetrasaccharide fragment (22) of linear (1→3)-α-D-glucan named pseudonigeran from Aspergillus niger  with 4,6-O-benzylidene-3-O-benzyl-2-O-(o-TAB)-D-glucopyranosyl trichloroacetimidate (1f**) was performed under α-directing conditions. Furthermore, the subsequent regioselective reductive ring-opening reaction to liberate the 4-hydroxy group afforded the pentasaccharide derivative (26) with the backbone structure of linear (1→4)-α-D-glucan (O-naphthylidene-3-O-triisopropylsilyl-2-O-(o-TAB)-D-glucopyranosyl trichloroacetimidate (1f*) under α-directing conditions to afford a hexasaccharide derivative -D-glucopyranosyl trichloroacetimidate (1f*) with methyl 2,3,4-tri-O-benzyl-D-glucopyranoside (4) under α-directing conditions, followed by the subsequent deprotection of the TIPS group, afforded the corresponding 3-OH disaccharyl acceptor (14). The subsequent α-selective glucosylation of the resultant acceptor with 3,4,6-tri-O-benzyl-2-O-(o-TAB)-D-glucopyranosyl trichloroacetimidate (1f) under α-directing conditions followed by a reductive ring-opening reaction to liberate the 6-hydroxy group and successive glycosylation under α-directing conditions afforded the tetrasaccharide fragment of a branched α-(1→6)-linked (1→3)-α-D-glucan (18) after hydrogenolysis.For the construction of a branched α-glucan fragment, the α-(1→3)-branch in the linear (1→6)-α-D-glucan backbone, one of the components of dextran, was examined via the initial introduction of the α-(1→3)-branch (26) of linear (1→4)-α-D-glucan, deprotection of the benzylidene group by TFA in CH2Cl2 afforded the 4,6-diol (24) at the nonreducing D-glucose residue (O-benzylidene-3-O-benzyl-2-O-(o-TAB)-D-glucopyranosyl trichloroacetimidate donor (1f**) under α-directing conditions afforded a fully protected branched hexasaccharide fragment (30) in one pot (The introduction of an α-(1→6)-branch into the linear (1→4)-α-D-glucan backbone was also examined via double α-glucosylation of the diol acceptor. After the synthesis of tetrasaccharide fragment -α-glucosylation between 6b and 31, the deprotection of the C-3-O-TIPS group of the resultant α-linked disaccharide (32) with TBAF in tetrahydrofuran (THF) afforded the corresponding disaccharide (33) with a C-3 hydroxy group (2-promoted glucosylation of the disaccharide acceptor (33) with the glucosyl donor (6b) gave the α,α-linked trisaccharide with high α-selectivity in a 71% yield. Repeating the deprotection and glucosylation steps yields the α,α,α-linked tetrasaccharide (34) stereoselectively, which was followed by the global deprotections via the desilylation and hydrogenolysis of 35 to complete the total synthesis of nigerotetraoside (37), a fragment of linear (1→3)-α-D-glucan. The desilylation of C-3-O-TIPS on tetrasaccharide (34) provided the acceptor (35), while the treatment of 34 with PdCl2 in methanol, followed by a reaction with CCl3CN and DBU, afforded the corresponding tetrasaccharyl trichloroacetimidate donor (36). Subsequent [4 + 4] coupling between the donor (36) and acceptor (35) with the ZnI2-promoted methodology under optimized conditions accomplished the synthesis of the target α-D-glucan nigerooctaoside (38) (2-promoted glucosylation to oligosaccharide donors and acceptors with multiple repeating units (tetrasaccharides) in a fragment condensation strategy for assembling higher-molecular-weight glucans.An alternative method for the synthesis of linear (1→3)-α-D-glucan, which constitutes the Pseudonigeran isolated from hodology . After txy group a. ZnI2-pide (38) b, sugges2-promoted glucosylation method has been shown by synthesizing branched α-glucan tetrasaccharides, such as (1→6)-α-branched (1→4)-α-D-glucan and (1→3)-α-branched (1→6)-α-D-glucan [The versatility of the ZnID-glucan  (Scheme 46) was initiated by the stereoselective ZnI2-mediated glucosylation of the 4-OH acceptor 23 with 2-O-benzyl-4,6-O-benzylidene-3-O-2-naphthylmethyl (NAP)-D-glucopyranosyl donor (6a) for an α-(1→4)-linked disaccharide (39), followed by the liberation of C-6-OH using the selective reduction protocol of 4,6-O-benzylidene acetal with BH3·THF and trimethylsilyl trifluoromethanesulfonate (TMSOTf). The second ZnI2-mediated α-(1→6)-glucosylation of the resultant acceptor (40) with the donor (6a) provided the linear α-D-glucan trisaccharide fragment (41) stereoselectively. The subsequent hydrolysis of 4,6-O-benzylidene acetal using TFA in DCM afforded 4,6-diol (42), and a treatment of the resultant 4,6-diol of 42 with NaH and BnBr, followed by the selective removal of the NAP ether of 43 with DDQ, afforded the C-4-OH (44) at the residue in the middle of the same trisaccharide linkage (44) was then glycosylated with a donor (6a) for branching under the ZnI2-mediated α-glucosylation conditions to provide the desired fully protected tetrasaccharide (45), which was followed by hydrogenolysis to complete the total synthesis of the branched α-glucan (46).The synthesis of α-(1→6)-branched (1→4)-α-D-glucan ( linkage c. The re47) was obtained by the stereoselective ZnI2-mediated glucosylation of the 6-OH acceptor (4) with donor (6a) followed by reductive ring-opening of naphthylidene acetal under BH3·THF and TMSOTf conditions, and the second stereoselective ZnI2-mediated glucosylation with the 3-O-TIPS-protected donor (6b). The liberation of the C-3-OH group by deprotection of the TIPS group of 47 with TBAF/AcOH afforded the corresponding 48, and the third ZnI2-promoted α-glucosylation with the donor (6a) afforded the desired (1→3)-α-(1→6)-α-D-glucan tetrasaccharide (18) after hydrogenolysis via 49 with exclusive α-stereoselectivity (To introduce the (1→3)-branching to the (1→6)-α-D-glucan backbone, (1→6)-α-D-glucan trisaccharide derivative  used conformationally counterbalanced donors between equatorial- and axial-rich forms. The automated α-glucan synthesis of up to 20 glucose residues was reported by Yamada [In this review, recent advances in stereoselective 1,2-y Yamada  and by Sy Yamada , respecty Yamada , the syn


Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a primary immunodeficiency disorder caused by heterozygous gain-of-function CXCR4 mutations. Myelokathexis is a kind of neutropenia caused by neutrophil retention in bone marrow and in WHIM syndrome is associated with lymphopenia and monocytopenia. The CXCR4 antagonist plerixafor mobilizes leukocytes to the blood; however, its safety and efficacy in WHIM syndrome are undefined.In this investigator-initiated, single-center, quadruple-masked phase III crossover trial, we compared the total infection severity score (TISS) as the primary endpoint in an intent-to-treat manner in 19 patients with WHIM who each received 12 months treatment with plerixafor and 12 months treatment with granulocyte CSF . The treatment order was randomized for each patient.P = 0.54). In exploratory endpoints, plerixafor was noninferior to G-CSF for maintaining neutrophil counts of more than 500 cells/μL (P = 0.023) and was superior to G-CSF for maintaining lymphocyte counts above 1,000 cells/μL (P < 0.0001). Complete regression of a subset of large wart areas occurred on plerixafor in 5 of 7 patients with major wart burdens at baseline. Transient rash occurred on plerixafor, and bone pain was more common on G-CSF. There were no significant differences in drug preference or quality of life or the incidence of drug failure or serious adverse events.Plerixafor was nonsuperior to G-CSF for TISS (Plerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and hematologic improvement, the infection severity results support continued study of plerixafor as a potential treatment for WHIM syndrome.Clinicaltrials.gov NCT02231879.This study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome presents in childhood, with severe congenital neutropenia (SCN), lymphopenia, hypogammaglobulinemia, recurrent otosinopulmonary and skin infections, and warts. Warts and hypogammaglobulinemia are incompletely penetrant, and additional uncommon phenotypes continue to be discovered –8. In alCurrent treatments include granulocyte CSF (G-CSF), the standard of care for SCN , and/or https://doi.org/10.1172/JCI164918DS1). One patient was disqualified during screening and before randomization because of G-CSF intolerance from bone pain. The 19 randomized participants included 11 female and 3 male adults (aged 20–57 years) and 2 female and 3 male children (aged 10–16 years). There were 9 White, 6 Hispanic, 2 African American, and 2 White/Native American individuals. CXCR4 mutations included R334X (n = 10), S338X (n = 2), E343X (n = 2), and 5 unique mutations  from October 14, 2014, through November 6, 2017 . The average number of infections was 3.89/patient-year on G-CSF and 2.84/patient-year on plerixafor, compared with the prestudy experience of 3 infections/patient-year in 11 patients with WHIM that was used to perform the primary endpoint power calculation. A ranked analysis of infection incidence as a secondary endpoint showed no difference between plerixafor and G-CSF , a weighted composite of predefined infection frequency and severity parameters  that are relevant to the participants’ experience. TISS was variable on each drug and between the two 1-year treatments and was not significantly lower for plerixafor than for G-CSF , gastrointestinal tract (n = 11), skin (n = 11), lower urinary tract (n = 6), and oral cavity (n = 4)  accounted for 86% of 114 total infections occurring during the 2 treatment phases; 89% of all infections occurred in 5 sites: the upper respiratory tract ( (n = 4) . The dis (n = 4) . Pathoge abscess . All butS. aureus axillary abscess in patient M13 on plerixafor for 1 week of intravenous antibiotics and drainage. Six additional patients visited an emergency department for 10 total infections (8 respiratory), 7 during G-CSF treatment and 3 during plerixafor treatment. The rate of hospitalization for infection/patient-year was 0.22 and 0.06 for G-CSF and plerixafor, respectively, and the rate of emergency department visits for infection/patient-year was 0.39 and 0.19 for G-CSF and plerixafor, respectively. Consistent with the G-CSF result, the rate of hospitalization for infection for the 19 patients for the 2 years preceding enrollment, when most patients were receiving G-CSF, was 0.24/patient-year. Lower respiratory tract infection is a major cause of hospitalization in patients with WHIM; however, no patients received a diagnosis of pneumonia on plerixafor, whereas 5 patients were diagnosed with pneumonia once each on G-CSF, all treated as outpatients. Antibiotics were prescribed for 89 nonhospitalized infections, 87% orally , and 12% topically (n = 5 on plerixafor and n = 6 on G-CSF)  .Although evaluation of lung function was not a prespecified study endpoint, all 19 patients had chest computerized tomography at baseline. Of 13 patients with lung abnormalities, 10 had mild-to-severe bronchiectasis, and 7 of the 10 had mild-to-severe pulmonary function test abnormalities, particularly diminished diffusion capacity of the lung for carbon monoxide; however, neither study drug significantly improved pulmonary dysfunction .All patients had severe baseline neutropenia and lymphopenia: the mean ± SEM ANC was 246 ± 42 , and the mean ± SEM absolute lymphocyte count (ALC) was 597 ± 48  .P = 0.023) , and 3 had success only on G-CSF, leading to a difference in proportion of success on G-CSF minus the proportion of success on plerixafor of 14/19 – 11/19 = 0.158 , which is significantly less than the prespecified margin of 0.40 (= 0.023) . Hence, = 0.023) . The ANC= 0.023) .P < 0.0001) ; thus, plerixafor was judged superior for maintaining the ALC above the prespecified threshold of 1,000 cells/μL for 1 year ( 0.0001) . During  0.0001) .The 4 patients who failed the ALC maintenance test during the treatment period for both drugs — M07, M09, M14, and M17 — all failed on plerixafor because they were study dropouts for that phase, as detailed previously. However, examination of data from the equilibration phase for all 4 patients and limited data from the treatment phase prior to dropout for patients M07 and M17 indicated that the ALC consistently exceeded 1,000 cells/μL on plerixafor for these patients  failed on plerixafor for different reasons. M09 had an adverse event during the equilibration phase that prevented entry into the plerixafor treatment phase. M04 and M06 both fell short of the prespecified 75% threshold for success (60% for M04 and 73% for M06). M04, M06, and M09 received a total actual daily dose of 92, 33, and 33 μg/kg/d of plerixafor, respectively, relative to the prespecified total target dose range for the protocol of 20–80 μg/kg/d.+ T cells matched the B cell pattern of severe baseline deficiency reversed by plerixafor but insensitive to G-CSF. Total CD4+ T cells were below the lower limit of normal for a subset of patients but could be increased to and maintained in the normal range for all patients by plerixafor. Central and effector memory CD4+ and CD8+ T cells followed the total CD4+ T cell response patterns. In contrast, although naive CD4+ and CD8+ T cell numbers were severely deficient at baseline in all but 1 patient, plerixafor was able to increase them in only 7 patients , 87% on the upper or lower extremities . Two addThe statistical analysis plan limited analysis of wart regression to treatment phase 1 because of the possibility of carryover effects. In this phase, there was detectable wart regression in 3 patients given plerixafor  and in 3 patients given G-CSF  . NeverthFor 4 patients  wart burden was unaffected by either drug. The other 9 patients (69%) improved on at least one treatment . Eight pOf the 69 wart areas identified at baseline in the 13 patients, 26 improved on plerixafor, 13 improved on G-CSF, 1 worsened on plerixafor, and 10 enlarged on G-CSF. Responses were highly heterogeneous in responding patients . For exaA plerixafor dose-response relationship for wart regression was not apparent . All 13 The 5 patients with major wart responses on plerixafor represented 71% of the subset of 7 patients with major wart burdens . These 5We previously published a survey of HPVs infecting immunodeficiency patients, including 10 patients from the present study before enrollment , 25. HerOf 62 HPVs identified, 16 were novel, all gammas, including 13 types and 3 species. HPV diversity correlated poorly with HPV disease burden. As extreme examples, patients M09 and M16 had low wart burdens yet harbored many HPV types, even in areas lacking warts. In particular, M09 had widespread plerixafor-induced psoriasiform lesions with no warts, from which we identified 8 different HPV types, including 5 γ and 3 β types. Likewise, M16 had a large pedunculated gluteal lipoma associated with 6 different HPV types, including 5 γ and one β type.Infection outcomes.Seven serious adverse events (SAEs) occurred among 6 patients, 1 during the open-label G-CSF posttreatment phase and 6 during a treatment phase  . Five trChlamydia sp. was detected by nucleic acid amplification of urethral exudate, which was treated with 1 g azithromycin. Arthritis resolved on a short course of prednisone and sulfasalazine, and repeat PCR 2 months later was negative for Chlamydia sp. He was then given masked G-CSF with return of disabling arthritis after 1 week. G-CSF was discontinued, and the symptoms resolved on prednisone and sulfasalazine. During 2.5 years of follow up, he was not treated with either G-CSF or plerixafor and had 3 mild flares limited to the wrists, which responded to short courses of low-dose prednisone. The patient was G-CSF and plerixafor naive prior to the study and did not have a prior history of arthritis, urethritis, or Chlamydia infection; rheumatoid factor was negative. His biological son has both juvenile rheumatoid arthritis and WHIM syndrome.A sixth SAE that was unanticipated and probably related to both study drugs was new onset reactive additive polyarthritis occurring in the wrists, hands, and knees of patient M14 on both plerixafor and G-CSF. He first noticed mild arthralgia in his hands 10 days after beginning open-label G-CSF during the screening phase. After starting plerixafor as study drug number 1, symptoms intensified and spread to involve the other joints. Plerixafor was stopped after 18 days. Workup revealed a friable urethra that was painful on gentle dacron swabbing, with bleeding and a yellowish discharge. One unanticipated noninfectious SAE occurred on G-CSF and was judged unrelated to the drug: a transient ischemic attack in patient M05 during outpatient gynecologic surgery. There was no prior history of cerebrovascular events, and she has had no recurrence through June 2023.Another 207 noninfectious adverse events in 58 descriptor categories occurred during the trial  . Bone paPatient M09, who had a family history of psoriasis, dropped out during the plerixafor equilibration phase because of extensive new onset psoriasis. The lesions completely resolved when plerixafor was discontinued and after a short course of topical corticosteroids and did not flare during treatment with G-CSF, which was given second. She subsequently experienced one other psoriasis flare over 5 years since the end-of-study visit, during a phase II clinical trial for WHIM syndrome of the chemically distinct small-molecule CXCR4 antagonist mavorixafor .A second group of less frequent, transient, and tolerated grade 1 or 2 adverse events that were considered probably or possibly related to a study drug and were not significantly different in frequency on the 2 drugs included headache in 9 patients, hyperuricemia in 7 patients, weight gain in 7 patients, nausea in 7 patients, and injection site reactions in 4 patients. The remaining adverse events were transient minor laboratory abnormalities or were mild and affected only a few patients.When asked at study completion and before unmasking, 10 patients favored plerixafor, 4 favored G-CSF, 3 had no preference, and 2 patients did not respond . Two patIn this crossover treatment study for WHIM syndrome, plerixafor was not superior to G-CSF for the primary endpoint of total infection severity scored over 1 year for each drug. The study had limitations for demonstrating a potential plerixafor advantage over G-CSF for controlling infections, including (a) the primary endpoint, which includes subjective measures of medical decision-making and judgment , as well as the simple classification of infections (sterile versus nonsterile site), and which does not require a pattern of recurrence typical of WHIM syndrome or exclude common infections unrelated to immunodeficiency that might attenuate a benefit signal; (b) using G-CSF, the standard-of-care in SCN , as the Since WHIM syndrome is a type of SCN, and G-CSF is the SCN standard-of-care, we chose G-CSF as the comparator instead of placebo. Nevertheless, it is important to point out that G-CSF efficacy has not specifically been assessed by a placebo-controlled clinical trial in WHIM syndrome. Restricting the primary endpoint to a particular type of infection or level of severity or else to recurrent infections would have imposed a level of arbitrariness on how to set boundaries and made adequately powering the study impractical. However, not doing so imposed a potential cost of attenuating an infection efficacy signal. Strikingly, few severe infections occurred on either drug. No patient was hospitalized during a treatment phase for respiratory infection, the most common cause of hospitalization in patients with WHIM , 4, 27. Our exploratory results confirm previous reports of clinically significant wart regression in patients with WHIM treated with plerixafor or the unrelated CXCR4 antagonist mavorixafor , 26 and + and CD8+ T cells, which were durably increased by plerixafor into the normal range for most patients. Additional studies will be needed, for example, of CXCR2 and CXCR4 expression, in both patients with WHIM and healthy individuals to investigate the apparent relative neutrophil mobilization insensitivity of patients with WHIM to plerixafor. Neutrophil responses in pediatric participants were weaker than those in adults, despite excellent lymphocyte responses, including for naive T cells, which conversely were poorly mobilized by plerixafor in most adults. Despite severe baseline lymphopenia, we documented normal proliferative T cell responses to mitogens, environmental organisms, and vaccine antigens at baseline and after plerixafor treatment . We speculate that WHIM immunodeficiency may protect from immunologically mediated disease in such predisposed patients. Bone pain was common in patients receiving G-CSF, despite the low doses used. Eczematous rash of the palms and soles was common on plerixafor, but it was transient and did not result in any dropouts. Side effects, especially bone pain, were most commonly cited by patients in deciding their drug preference, which trended in favor of plerixafor. This result from the study will be important during informed decision making between physicians and patients.The lower age limit for participation (10 years of age) precluded our ability to judge the safety and efficacy of plerixafor in younger children. Our findings, together with recent results suggesting that early diagnosis may improve outcomes in WHIM syndrome , may jusIn conclusion, plerixafor was not superior to G-CSF for control of infection severity, the primary endpoint. The study was not designed to answer whether plerixafor is noninferior to G-CSF for infection severity; however, no differences between the G-CSF and plerixafor arms were found for any infection outcome measures. The exploratory endpoints suggested that plerixafor may be noninferior to G-CSF for durably increasing the ANC and may have an advantage over G-CSF for elevating the ALC, for wart regression, and for limiting bone pain. Dermatitis or arthritis severe enough to stop treatment occurred in 3 patients while on plerixafor and 1 patient while on G-CSF.The study has a randomized, quadruple-masked , crossover design comparing plerixafor with G-CSF, and it was conducted at the NIH-CC. The trial was investigator initiated and designed and was sponsored by the National Institute of Allergy and Infectious Diseases Division of Clinical Research. Additional details can be found in the CXCR4 mutation damaging the C-terminus of CXCR4. A history of treatment with G-CSF or plerixafor was not disqualifying, and continuation of prophylactic antibiotics and immunoglobulin supplementation according to best medical practice was allowed. Additional details are provided in the Eligibility criteria included a 10- to 75-year age range, a baseline ANC of less than 1,500 cells/μL, a history of recurrent infections, and a Cxcr4-knockout mice are nonviable . Either the Pharmaceutical Development Section of the NIH-CC Pharmacy or Integrity Bio Inc. transferred the drugs undiluted under cGMP conditions into unmarked borosilicate syringes in 5 different predefined amounts: 15, 22.5, 36, 54, and 75 μg G-CSF  and 800, 1,200, 1,800, 2,600, and 3,800 μg plerixafor . These 2 ranges were predefined to deliver target doses ranging from approximately 0.25 to 2.0 μg/kg BiD for G-CSF and approximately 10 to 40 μg/kg BiD for plerixafor for the body weight range anticipated for the study participants. The predefined target dose ranges for both drugs were expected to be sufficient, based on previous experience in treating patients with WHIM, who do not have a myeloid block and have mobilizable leukocyte pools , 18–20, onviable . It was onviable . BiD dosonviable  and was For patients already taking open-label G-CSF at enrollment, the unmasked prefilled G-CSF syringe amount prescribed to start the screening phase was judged based on the preenrollment dose, the preenrollment ANC response, and patient weight. Those not already taking G-CSF at enrollment started the screening phase using the syringe containing either the lowest or second lowest G-CSF dose. Dose adjustments using the 5 available syringe amounts were made during the screening phase if necessary, guided by periodic blood count assessments, to increase the morning dose trough ANC into the predefined target range of 500–1,500 cells/μL. To start the masked and randomized equilibration phases, the masked principal investigator selected both a prefilled G-CSF syringe dose based on the patient’s screening phase response and a prefilled plerixafor syringe that would deliver a dose within the lower portion of the target dose range, i.e., approximately 10–20 μg/kg BiD. The unmasked pharmacist then dispensed the correct syringe option based on the randomization. The initial G-CSF dose in this phase was, in most cases, the same as the dose the patient had already been receiving at the end of the screening phase. From these starting doses, adjustments were made during the equilibration phase using the same prescribing procedure for the other 4 prefilled syringe amounts for each drug, guided by masked ANC assessments every 2 weeks before the morning dose, until the ANC reached at least 500 cells/μL. Patients who failed to reach this threshold by 8 weeks were declared drug failures and were switched to the second drug. Patients who succeeded during the equilibration phase were continued on the effective dose for a 12-month treatment phase. The dose could be further adjusted within the prespecified range for each drug during the treatment phase if the ANC fell below 500 or above 7,500 or to mitigate an adverse event thought to be related to the drug. Patients unable to tolerate a study drug or who met prespecified failure criteria were switched in the first treatment period to the alternate agent or in the second treatment period to open-label G-CSF.The prespecified primary efficacy endpoint was the difference between the two 12-month treatment periods for the TISS, a weighted composite of predefined infection frequency and severity inputs defined for this study. Records of each medical encounter for infection were collected from the treating health care provider and scored by the study team according to the predefined point system shown in The points for each parameter in each column were added for each infection to produce an infection severity score, which could range from 1 to 10. For each patient, infection severity scores for all infections occurring during a treatment phase were added to generate a TISS for that phase that was then compared with the TISS for the second treatment phase. Additional details are provided in the Ordered secondary endpoints included sustained ANC and ALC improvement; infection incidence; antibiotic treatment duration; wart regression; and quality of life based on the 36-Item Short Form Survey, version 2 instrument . SustainClinical photography and dermatologist assessments of warts were obtained at baseline on day 0 of the equilibration phase as well as at the month 0, 4, 8 and 12 visits during the treatment phase. Two masked dermatologists scored the percentage change in baseline wart area at each of the 4 visits during each treatment phase. A complete response was defined as visible absence at the month 12 visit of a wart area defined at the baseline visit. Because carryover effects on warts were possible during drug crossover, the prespecified statistical analysis plan compared improvement only for the first treatment phase. HPV identification was as previously reported , 35.Blood for quantitative immunoglobulin and lymphocyte subset assessments was obtained at the NIH-CC before the first study drug dose on day 0 of each equilibration phase and approximately 3 hours after the morning dose at the month 0, 4, 8, and 12 visits of each treatment phase. Immunophenotyping was performed by the Department of Clinical Immunology at the NIH-CC using freshly isolated PBMCs. Cells were washed with PBS, fixed with 1.0% formaldehyde, resuspended in PBS, and then stained for cell surface expression of CD45, CD3, CD4, CD8, CD14, CD56, CD45RA, CD62L, and CD19 using directly labeled monoclonal antibodies . LymphocWe report all adverse events for all study phases.S for each participant, defined as follows: S = (TISS during treatment phase 1 – TISS during treatment phase 2), for a patient who did not have a drug failure and had complete follow up. Patients who failed to complete a treatment phase were given the worst score for that phase. Because the order of drug administration was randomized, if there were phase effects or carryover effects, the methods are still valid. A 2-sample Wilcoxon’s rank sum test analyzed TISS differences between plerixafor and G-CSF at the 2-sided 0.05 level. If significant, we would proceed to test the prespecified secondary outcomes in the predefined order using the fixed-sequence method, each at the 1-sided 0.025 level adjusting for multiple comparisons.Participant sample size of 20 was defined from retrospective frequency and severity data on infections in 11 patients with WHIM treated with G-CSF at the NIH-CC for 1 year  while on G-CSF minus the proportion of successes while on plerixafor, and we prespecified a noninferiority margin of 0.40, which was estimated to be about 50% of the size of the effect of G-CSF versus placebo. For quantifying CIs on differences in success proportions for maintaining the ANC and ALC above predetermined levels on drug, we used a method that accounts for the pairing due to the crossover design and is valid for small samples . We switThe Institutional Review Board of the National Institute of Allergy and Infectious Diseases approved the study. All patients gave written informed consent prior to participation and for the use of clinical photographs.Values for all data points in graphs are reported in the DHM, DF, MPF, HLM, and PMM designed the study and developed the protocol. CBB and DVP acquired, analyzed, and interpreted HPV genomic data. KRC analyzed bone marrow data. DHM, PMM, PJG, EWC, JJD, MAM, PS, DV, EC, HJK, CB, and JDK acquired and analyzed clinical data. SDR supervised flow cytometry. DBK supervised T cell proliferation and antibody assays. DF, MPF, DHM, and PMM established the statistical analysis plan. DF, MPF, and PMM performed statistical analyses. PMM made the decision to publish the paper. The paper was written mainly by PMM and MPF with contributions from all authors.


Single crystal X-ray diffraction revealed that TC[4]TT adopts an alternative octagonal form recessed to the inner side. Its internal cavity included small solvents, such as chloroform and carbon disulfide. Due to its polygonal geometry, TC[4]TT laminated in a honeycomb-like pattern with a porous channel. Furthermore, TC[4]TT showed fluorescence and phosphorescence emission in a CH2Cl2 solution at ambient and liquid nitrogen temperatures. Both emission bands were slightly redshifted compared with those of the reference compounds (di(thanthren-2-yl)sulfane (TT2S) and thianthrene (TT)). This work describes a sulfur-containing thiacalixheterocycle-based macrocyclic system with intriguing supramolecular chemistry based on molecular tiling and photophysical properties in solution.Sulfur-containing macrocycles have attracted substantial interest because they exhibit unique characteristics due to their polygonal ring-shaped skeleton. In this study, a thianthrene-based cyclic tetramer with the sulfur linker, thiacalix[4]-2,8-thianthrene (TC[4]TT), was successfully prepared from a cyclo- Thiacalixarenes are categorized as thioether-type macrocyclic compounds, which can adopt unique polygonal geometries by connecting aromatic hydrocarbons with sulfur linkers ,2. The cWe focus on the 1,4-dithiin-embedded heterocycle compound, thianthrene  was treated with turbo Grignard reagent to selectively translate the iodine of 1, and then, the generated arylmagnesium compound was reacted with S-methyl benzenesulfonothioate as an electrophile to afford (5-bromo-2-chlorophenyl)(methyl)sulfane (2) quantitatively. When Compound 2 was oxidized using m-chloroperbenzoic acid (mCPBA), 4-bromo-1-chloro-2-(methylsulfinyl)benzene (3) was obtained quantitatively. Subsequently, a Pd-catalyzed homocoupling reaction using potassium thioacetate as a sulfur source TT is illustrated in r source  of 3 aff ESI-MS, . However TT unit , and simspectrum . Thus, t3 and CS2. Both crystals belonged to the I2 space group with a monoclinic crystal system. The inwardly folded (−1 (2S (corresponding angles: 137.1(1) and 130.4(1)°). The TT units distorted as a result of macrocyclization. The distances between the sulfur bridges were 9.71 and 10.4 Å, respectively. Although the distance between two flared TT units was 12.8 Å, the distance was 5.62 Å at the narrowest part and 9.70 Å at the widest parts of the collapsed TT units (3 and CS2) were included in the cavity of TC[4]TT, and the composition ratio of compound and solvent was 1:2 (3)2 and (TC[4]TT)(CS2)2). For CHCl3 and CS2, the two molecules in the cavity fit in a V-shape along with the lamination direction. Although we attempted to incorporate solvents with different sizes, such as benzene, 1,4-dioxane, and chlorobenzene, into TC[4]TT, parsable crystals were not obtained. In donor–acceptor-type complex formations with C60 and C70, distinct complexation could not be observed. This result shows that TC[4]TT can selectively capture relatively small molecules in the crystal state. Thus, TC[4]TT can expect selective inclusion with small organic molecules and metal ions similar to thiacalixarene derivatives. Notably, intermolecular interactions between TC[4]TT and each encapsulated solvent were not observed, suggesting that the solvent molecules just fit in the cavity. Conversely, differences were observed in the intermolecular packing forces acting among TC[4]TT, while (TC[4]TT)(CHCl3)2 and (TC[4]TT)(CS2)2 were the same crystal system. The clathrate crystal of TC[4]TT and CHCl3 contains some C–H···π interactions and C–H···S contacts TT)(CS2)2. The crystal of (TC[4]TT)(CS2)2 was packed more densely than that of (TC[4]TT)(CHCl3)2. Thus, coupled with the pseudo hexagonal geometry consisting of imminent sulfur of TT and the linker, TC[4]TT was arranged in a honeycomb style with a channel structure due to molecular tiling. These results suggest that TC[4]TT exhibits adsorption and transport properties and shows potential as an organic porous solid material.Single crystals of TC[4]TT were obtained by slowly evaporating CHCllded  plates during purification. The CH2Cl2 solution of TC[4]TT (c = 2.0 × 10−5 mol L−1) showed an absorption maximum at 271 nm with broad shoulder bands at 290–360 nm, which could be ascribed to the π–π* transitions (ε) at λmax = 271 nm was 92,500 L mol−1 cm−1, higher than those of TT2S and TT , depending on the number of TT units. Furthermore, the absorption wavelength of TC[4]TT was slightly redshifted compared with those of TT2S and TT (λmax = 268 and 258 nm). This redshift stems from a decline in the gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), as shown in 0 → S2, S3, and S8 electronic transitions (0 → Sn (n > 1) of TC[4]TT were lower than those of TT2S . The quantum yields (Φ) of TC[4]TT and TT2S were 7 and 6%, respectively. Although these values were slightly higher than that of TT (Φ = 3%), the emission efficiency remained low. Thus, the nonradiative process mostly results from the geometric vibrations of the TT unit at the excitation despite the advantages of a rigid skeleton generated from macrocyclization. That is, TC[4]TT possesses a highly flexible molecular geometry.TC[4]TT generates a blue emission on the TLC plate under irradiation with a UV lamp (λ = 365 nm). In a dilute CHnditions b. Simila2Cl2 solution of TC[4]TT at liquid nitrogen temperature (77 K) showed a new emission band at λmax = 516 nm in the long wavelength region. The reference compounds TT2S and TT also exhibited redshifted emission bands at λmax = 508 and 504 nm at 77 K. These low-temperature spectra were measured with a 15 ms delay, and the lifetimes were 45 ms for TC[4]TT and 34 ms for TT2S, which could be identified as phosphorescence emission. The phosphorescence emission maximum of TC[4]TT was gradually redshifted, which could indicate that the energy gap of the lowest singlet (S1) and triplet excited state (T1) was narrower than those of TT2S and TT. The efficient intersystem crossing process might be prompted by rigidity arising from macrocyclization with the sulfur linker. The quantum chemical calculation supported that the energy gap between S1 and T1 of TC[4]TT is 0.629 eV. This was lower than those of TT2S (0.795 eV) and TT  are included in the cavity, which exhibits unusual inclusiveness, as with thiacalixarene derivatives. That is, the compound can be applied to adsorbed porous materials. Intriguingly, the diluted CH2Cl2 solution of TC[4]TT demonstrates fluorescence emission at ambient temperature and phosphorescence emission at liquid nitrogen temperature. Notably, phosphorescence emission bands are redshifted compared to those of thianthrene and its sulfur-bridged dimer. This result indicates that macrocyclization by a sulfur bridge might load an efficient intersystem crossing system for phosphorescence emission. Thus, we found that TC[4]TT can be utilized as a chemical sensor. Molecular recognition ability, solid-state phosphorescence emission, and electrochemical properties are currently being studied.In conclusion, we successfully prepared a thianthrene-based cyclic tetramer linked with sulfur, thiacalix[4]-2,8-thianthrene (TC[4]TT), by acid-induced intramolecular condensation of a cyclo-1H (400 or 600 MHz) and 13C (100 or 150 MHz) nuclear magnetic resonance spectra were recorded using Bruker AVANCE 400 and 600 instruments. The following abbreviations were used to describe the multiplicities: singlet (s); doublet (d); doublet of doublets (dd); and multiplet (m). The diffraction data for TT2S , (TC[4]TT)(CHCl3)2 , and (TC[4]TT)2(CS2)2  were collected using a Rigaku XtaLAB Synergy-S system with multilayer mirror-monochromatized CuKa radiation (l = 1.54184 Å) at Kitasato University. Raw frame data were integrated using CrysAlisPro software + 235.9057; found 235.9058.Synthesis of .3 mmol)  in dry T3. Compound 2 , mCPBA , NaHCO3 , and CH2Cl2 (50 mL) were mixed in a 200 mL recovery flask. The mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with Na2S2O3aq., and then the organic layer was extracted with CH2Cl2 and dried over MgSO4. After filtration, the solution was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using EtOAc as an eluent to afford 3  as a colorless block in 99% yield. Mp = 77–78 °C. 1H NMR  δ 8.07 , 7.57 , 7.27 , 2.84 . 13C NMR  δ 145.6, 135.1, 131.2, 128.6, 128.4, 122.4, and 41.6. UV–vis  λmax (ε) 236  nm. IR (KBr) 3072, 3053, 3006, 1697, 1443, 1430, 1366, 1302, 1233, 1142, 1104, 1072, 1058, 1023, 971. 955, 895, 812, 693, 681, 555, 542, 451, and 403 cm−1. HRMS : m/z calcd for C7H6BrClOS [M + H]+ 252.9084; found 252.9087.Synthesis of 4 from 3. Compound 3 , Pd(dba)2 , dppf , KSAc , and K3PO4  were added to a 30 mL Schlenk tube in toluene (1.1 mL) and acetone (0.5 mL) under an argon atmosphere. The reaction mixture was stirred for 6 h under reflux. After cooling to ambient temperature, the suspension was quenched with NH4Claq. The aqueous layer was extracted with Et2O, and the organic layer was washed with brine and dried over MgSO4. The organic phase was passed through celite and concentrated. The residue was purified by column chromatography on silica gel using EtOAc as an eluent to afford 4  as a colorless needle in 43% yield. Mp = 145–147 °C. 1H NMR  δ 7.93 , 7.88 , 7.43–7.34 , 2.84 , 2.83 . 13C NMR  δ 145.3, 145.2, 136.14, 136.13, 134.3, 134.2, 130.94, 130.88, 129.13 129.10, 127.5, 127.4, 41.8, and 41.7. UV–vis  λmax (ε) 290 , 259  nm. IR (KBr) 3446, 3065, 2996, 2912, 1636, 1567, 1445, 1415, 1365, 1291, 1247, 1146, 1088, 1062, 1023, 960, 897, 830, 699, 557, 459, 413, and 402 cm−1. HRMS : m/z calcd for C14H12Cl2O2S3 [M + H]+ 378.9449; found 378.9450.Synthesis of 5. Compound 2 , Pd(dba)2 , dppf , KSAc , and K3PO4  were added to a 50 mL Schlenk tube in toluene (8.1 mL) and acetone (4.0 mL) under an argon atmosphere. The reaction mixture was stirred for 6 h under reflux. After cooling to ambient temperature, the suspension was quenched with NH4Claq. The aqueous layer was extracted with Et2O, and the organic layer was washed with brine and dried over MgSO4. The organic phase was passed through celite and concentrated. The residue was purified by column chromatography on silica gel using EtOAc/hexane  as the eluent to afford 5  as a colorless needle in 74% yield. Mp = 100–102 °C. 1H NMR  δ 7.26 , 7.01 , 6.99 , 2.41 . 13C NMR  δ 139.3, 134.5, 130.9, 130.0, 127.8, 127.3, and 15.1. UV–vis  λmax (ε) 260  nm. IR (KBr) 3059, 2985, 2916, 1884, 1559, 1454, 1428, 1361, 1269, 1247, 1155, 1118, 1095, 1030, 956, 857, 845, 815, 674, 555, 464, and 434 cm−1. HRMS : m/z calcd for C14H12Cl2S3 [M]+ 345.9473; found 345.9471.Synthesis of 4 from 5. Compound 5 , mCPBA , NaHCO3 , and CH2Cl2 (5 mL) were added to a 50 mL recovery flask. The mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with Na2S2O3aq., and then the organic layer was extracted with CH2Cl2 and dried over MgSO4. After filtration, the solution was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using EtOAc as an eluent to afford 4  as a colorless block in 54% yield.Synthesis of 7 was prepared according to the bromination of thianthrene + 461.9694; found 461.9691.Synthesis of di(thianthren-2-yl)sulfane , 4,4′-thiobisbenzenethiol , K2CO3 , and dry DMA (64 mL) were added to a 100 mL Schlenk tube under an argon atmosphere. The mixture was stirred at 150 °C for 2 days. After cooling to ambient temperature, the mixture was poured into 10% acetic acid (160 mL). The water layer was extracted with CH2Cl2, and the organic phase was washed with NaHCO3aq. and then dried over MgSO4. The organic solution was evaporated under reduced pressure. After the ocherous powder was collected, 329 mg of crude product involving Compound 6 was obtained. In the next step, the crude product, P2O5 , and trifluoromethanesulfonic acid (3.5 mL) were added to a 50 mL two-necked recovery flask under an argon atmosphere. The reaction mixture was stirred at 65 °C for 2 days and then poured into ice water. After the precipitates were collected by filtration, the residue was dissolved in pyridine (25 mL) and refluxed for 24 h. The reaction mixture was cooled to ambient temperature, and MeOH was added. The resulting precipitate was collected and then subjected to column chromatography on silica gel using CS2 as the eluent to afford thiacalix[4]thianthrene  as a colorless block in 5% yield from Compound 4 in 2 steps. Mp = 203 °C (decomp.). 1H NMR  δ 7.31 , 7.19–7.15 , 13C NMR  δ 136.6, 135.2, 134.5, 130.5, 130.0, and 128.9. UV–vis  λmax (ε) 271  nm. IR (KBr) 1557, 1442, 1363, 1252, 1107, 905, 712, 731, and 450 cm−1. HRMS : m/z calcd for C48H24S12 [M]+ 983.8521; found 983.8527.Synthesis of thiacalix[4]thianthrene (TC[4]TT). Compound