An expedient synthesis of spiroketals: model studies for the calyculin C16–C25 fragment
Abstract A new short strategy to prepare the spiroketal fragment of calyculins is presented. A novel Seyferth–Gilbert type homologation of hindered lactols to the corresponding alkynes has been achieved for the first time. The spirocyclization was achieved efficiently via a DIHMA (double intramolecular hetero-Michael addition) process of this hindered ynone. The spirocyclization rate is not dependent on the stereochemistry of the alkoxy substituent in the oxolane ring.
Synthesis of [3.3.1] bicyclic compounds by a Brønsted acid catalysed double intramolecular Michael addition.
One of the current challenges in organic chemistry is the development of tandem reactions (domino or cascade reactions) that provide complex molecules from readily available starting compounds. A major subject of research in this field is the exploration of new tandem reactions promoted by a single catalyst. In particular, some elegant organocatalytic cascade reactions promoted by both chiral amines or Brønsted acids have been developed. The double intramolecular hetero Michael addition (DIHMA) of a diol upon an ynone is an effective approach to give several ketal derivatives. In these reactions, two hydroxyl groups act as the nucleophilic counterpart that adds to the b carbon of the alkyne of the ynone (Scheme 1 b). These DIHMA reactions may be considered as a particular case of the double intramolecular Michael addition (DIMA) in which two general nucleophiles add to an ynone (Scheme 1 a). However, as far as we know, this interesting DIMA reaction has not been expanded further than those particular cases in which both nucleophiles are hydroxyl groups (DIHMA). In this context we were attracted by the work developed by C. J. Forsyth et al. , about the use of the DIHMA reaction for the synthesis of 2,9-dioxabicycloACHTUNGTRENNUNG[3.3.1]nonane derivatives. We thought that simple 9oxabicycloACHTUNGTRENNUNG[3.3.1]nonane derivatives could be obtained by an unexplored double intramolecular Michael addition of an oxygen-centred and a carbon-centred nucleophile to an ynone (Scheme 1 c). Note that we had previously evaluated another approach to access these types of bicyclic compounds. Thus, by using carbophilic Lewis acids (p acids) we were able to activate simple alkynes that favour a double addition of two different nucleophiles to a non-functionalised C C triple bond. One of the main drawbacks of this strategy is the necessity of using precious organo–transition-metal catalysts as promoters of the reaction. We thought that we could surpass this problem by applying the DIMA strategy above because, in principle, the metallic catalyst could be substituted by cheaper and easily handled Brønsted acids. Also note that the mode of activation of Brønsted acids is different from that of the p acids because these activate the alkyne and the Brønsted acids activate the carbonyl group that favours the double Michael addition. Herein we wish to detail the first examples of double intramolecular Michael addition of two different nucleophiles [a] Dr. A. Mendoza, P. Pardo, Dr. F. Rodr guez, Prof. Dr. F. J. FaÇan s Instituto Universitario de Qu mica Organomet lica “Enrique Moles” Unidad Asociada al C.S.I.C., Universidad de Oviedo Juli n Claver a, 8, 33006 Oviedo (Spain) Fax: (+34) 985103446 E-mail : fjfv@uniovi.es frodriguez@uniovi.es Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201001109. Scheme 1. Concept of the double intramolecular Michael addition (DIMA), previous DIHMA strategies and our proposal.
Single step formation of biocompatible bimetallic alloy nanoparticles of gold and silver using isonicotinylhydrazide.
Manufacturing nanoparticles with controlled physicochemical properties using environment-friendly routes have potential to open new prospects for a variety of applications. Accordingly, several approaches have been established for manufacturing metal nanoparticles. Many of these approaches entail the use of hazardous chemicals and could be toxic to the environment, and cannot be used readily for biomedical applications. In the present work, we report a single step bio-friendly approach to formulate gold (Au), silver (Ag), and Au-Ag alloy nanoparticles with desired surface corona and composition using isonicotinylhydrazide (INH) as a reducing agent. INH also functioned as a stabilizing agent by enabling a surface corona around the nanoparticles. Remarkably, within a single step INH could also provide a handle in regulating the composition of Au and Ag in bimetallic systems without any additional chemical modification. The physicochemical and surface properties of the different nanoparticles thus obtained have been examined by analytical, spectroscopic and microscopic techniques. Cell cytotoxicity (release of lactate dehydrogenase), cell viability and intracellular reactive oxygen species (ROS) assays confirmed that the Au, Ag, and Au-Ag bimetallic nanoparticles prepared with INH are biocompatible. Finally, the presence of organic surface corona of INH on the nanoparticles was found to impart nanozyme activity and antimycobacterial sensitivity to the nanoparticles.