Ethers
United States Patent 1 Kelly 1 Apr. 22, 1975 ETHERS [75] Inventor: Robert C. Kelly, Kalamazoo. Mich.  
 [73] Assignee: The Upjohn Company, Kalamazoo.  
 Mich.  
  22 Filed: Dec. 15,1972  
  21 Appl.No.:3l5,690  
  Related U.S. Application Data [60] Division of Ser. No. l8l.246. Sept. l6. l97l. Pat.  
 No. 3.71 1.5 l5. which is a continuation-in-part of Scr, No. 93,483. Nov. 27. 1970. abandoned.  
 [52] U.S. Cl. 260/3401; 260/340.9; 260/611 F [51] Int. Cl C07d 13/04 [58] Field of Search 260/340]. 340.9, 6H F Primary E.\un1inw&#39;Henry R. Jiles Assistant Examiner-Robert T. Bond Attorney, Agent, or FirmMorris l... Nielsen [57] 4 ABSTRACT Process for preparing l bycyclic lactone diols of the formula 3 Claims, No Drawings ETHERS This is a division of application Ser. No. 181,246, filed Sept. I6, 1971, now U.S. Pat. No. 3,711,515, which was a continuation-in-part of application Scr No. 93,483, filed Nov. 27, 1970, now abandoned.  
 BACKGROUND OF THE INVENTION This invention relates to a process for preparing intermediates useful in the preparation of prostaglandins. (hereinafter identified as PGE- PGFga etc.) and to a process for preparing racemic (dl) and optically active PGE and PGF and their enantiomorphs, their IS-epimers, and their alkyl esters.  
  Previously, the preparation of an intermediate bicyclic lactone diol of the formula was reported by E. J. Corey et al., J. Am. Chem. Soc. 91, 5675 (1969), and later disclosed in an optically active form by E. J. Corey et al., J. Am. Chem. Soc. 92, 397 (I970). Conversion of this intermediate to PGE and PGF either in dl-form or optically active form, was disclosed in those publications.  
  It is well known that the prostaglandin structures have several centers of asymmetry and therefore exist as stereoisomers (see Nugteren et al., Nature 212, 3839 (I966); Bergstrom et al., Pharmacol. Rev. 20, 1 (I968)). Each formula for PGE PGF PGE and PGF herein, viz. XVI, XXII, XXIV, and XXVI. wherein shows attachment of hydroxyl in the S configuration, represents a molecule of the optically active naturally-occurring form of the prostaglandin. The mirror image of each formula represents a molecule of the enantiomorphic form of that prostaglandin. Thus, for example, ent-PGE refers to the enantiomorph of PGE The racemic or dl&#34; form of the prostaglandin consists of equal numbers of two types of molecules, e.g., a natural-configuration prostaglandin and its enantiomorph. If one of the optically active isomers has dextro optical rotatory power, the other has an,equal degree of Iaevo optical rotatory power. A racemic mixture of equal quantities of dand l-isomers exhibits no optical rotation. The reaction of the components of a racemic mixture with an optically-active substance results in the formation of diastereomers having different physical properties, e.g. degree of solubility in a solvent. Another term used herein is IS-epimer. When referred to one of the above prostaglandins, it identifies a molecule having the opposite configuration at the 15 carbon atom. Thus, l 5-epi-PGE refers to the product having the R configuration at carbon as compared with the S configuration for PGE PGE and PGF and their esters, acylates, and pharmacologically acceptable salts, are extremely potent in causing various biological responses. For that reason, these compounds are useful for pharmacological purposes. See, for example, Bergstrom et,al., Pharmacol. Rev. 20, 1 (I968), and references cited therein. A few of those biological responses are systemic arterial blood pressure lowering in the case of the PGE and PGF- compounds as measured, for example, in anesthetized (pentobarbital sodium) pentollinium-treated rats with indwelling aortic and right heart ca&#39;nnulas; pressor activity, similarly measured, for the PGF compounds; stimulation of smooth muscle as shown, for example, by tests on strips of guinea pig ileum, rabbit duodenum, or gerbil colon; potentiation of other smooth muscle stimulants; antilipolytic activity as shown by antagonism of epinephrine-induced mobilization of free fatty acids or inhibition of the spontaneous release of glycerol from isolated rat fat pads; inhibition of gastric secretion in the case of the PGE compounds as shown in dogs with secretion stimulated by food or histamine infusion; activity on the central nervous system; decrease of blood platelet adhesiveness as shown by pIatelet-to-glass adhesiveness, and inhibition of blood platelet aggregation and thrombus formation induced by various physical stimuli, e.g., arterial injury, and various biochemical stimuli, e.g., ADP, ATP, serotonin, thrombin, and collagen; and in the case of the PGE compounds, stimulation of epidermal proliferation and keratinization as shown when applied in culture to embryonic chick and rat skin segments.  
  Because of these biological responses, these known prostaglandins are useful to study, prevent, control, or alleviate a wide variety of diseases and undesirable physiological conditions in birds and mammals, including humans, useful domestic animals, pets, and zoological specimens, and in laboratory animals, for example, mice, rats, rabbits, and monkeys.  
  For example, these compounds, and especially the PGE- compounds, are useful in mammals, including man, as nasal decongestants. For this purpose, the compounds are used in a dose range of about 10 pg. to about 10 mg. per ml. of a pharmacologically suitable liquid vehicle or as an aerosol spray, both for topical application.  
  The PGE compounds are useful in mannals, including man and certain useful animals, e.g., dogs and pigs, to reduce and control excessive gastric secretion, thereby including or avoiding gastrointestinal ulcer for mation, and accelerating the healing of such ulcers already present in the gastrointestinal tract. For this purpose, the compounds are injected or infused intravenously, subcutaneously, or intramuscularly in an infusion dose range about 0.1 ug. to about 500 pg. per kg. of body weight per minute, or in a total daily dose by injection or infusion in the range about 0.1 to about 20 mg. per kg. of body weight per .day, the exact dose depending on the age, weight, and condition of the patient or animal, and on the frequency and route of administration.  
  The PGE and PGF compounds are useful whenever it is desired to inhibit platelet aggregation, to reduce the adhesive character of platelets, and to remove or prevent the formation of thrombi in mammals, including man, rabbits, and rats. For example, these compounds are useful in the treatment and prevention of myocardial infarcts, to treat and prevent post-operative thrombosis, to promote patency of vascular grafts following surgery, and to treat conditions such as atherosclerosis, arteriosclerosis, blood clotting defects due to lipemia, and other clinical conditions in which the underlying etiology is associated with lipid imbalance or hyperlipidemia. For these purposes, these compounds are administered systemically, e.g., intravenously, subcutaneously, intramuscularly, and in the form of sterile implants for prolonged action. For rapid response, es-  
  tracorporeal circulation and perfusion of isolated body portions, e.g., limbs and organs, whether attached to the original body, detached and being preserved or prepared for transplant, or attached to a new body. During these circulations and perfusions, aggregated platelets tend to block the blood vessels and portions of the circulation apparatus. The blocking is avoided by the presence of these compounds. For this purpose, the compound is added gradually or in single or multiple portions to the circulating blood, to the blood of the donor animal, to the perfused body portion, attached or detached, to the recipient, or to two or all of-these at a total steady state dose of about 0.001 to mg. per liter of circulating fluid. It is especially useful to use these compounds in laboratory animals, e.g., cats, dogs, rabbits. monkeys, and rats, for these purposes in order to develop new methods and techniques for organ and limb transplants. I  
  PGE compounds are extremely potent in.causing stimulation of smooth muscle, and are also highly active in potentiating other known smooth muscle stimulators. for example, oxytocic agents, e.g., oxytocin,&#39;and  
 the various ergot alkaloids including derivatives and analogs thereof. Therefore PGE for example, is useful in place of or in combination with less than usual amounts of these known smooth muscle stimulators, for example, to relieve the symptoms of paralytic ileus, or to control or prevent atonic uterine bleeding after abortion or delivery, to aid in expulsion of the placenta, and during the puerperium. For the latter purpose, the POE- compound is administered by intravenous infusion immediately after abortion or delivery at a dose in the range about 0.01 to about 50 pg. per kg. of body weight per minute until the desired effect is&#39;obtained. Subsequent doses are given by intravenous, subcutaneous, or intramuscular injection or infusion during puerperium in the range 0.01 to 2 mg. per kg. of body weight per day, the exact dose depending on the&#39;age, weight, and condition of the patient or animal.  
  The PGE compounds are useful as hypotensive agents to reduce blood pressure in mammals including man. For this purpose, the compounds are administered by intravenous infusion at the rate about 0.0] to about 50 pg. per kg. of body weight per minute, or in single or multiple doses of about 25 to 500 pg. per kg. of body weight total per day.  
  The PGE and PGF compounds are useful in place&#39;of oxytocin to induce labor in pregnant female animals, including man, cows, sheep, andpigs, at or near term, or in pregnant animals with intrauterine death of the fetus from about weeks to term. For this purpose, the compound is infused intravenously at a dose 0.01 to 50 #g. per kg. of body weight per minute until or near the termination of the second stage of labor, i.e., expulsion of the fetus. These compounds are especially useful when the female is one or more weeks post-mature and natural labor has not started, or 12 to 60 hours after the membranes have ruptured and natural labor has not yet started.  
  The PGE and PGF compounds are useful for controlling the reproductive cycle in ovulating female mammals, including humans and other animals. For that purpose, PGF for example, is administered systemically at a dose level in the range 0.01 mg. to about 20 mg. per kg. of body weight, advantageously during a span of time starting approximately at the time of ovulation and ending approximately at the time of menses or just prior to menses. Additionally, expulsion of an embryo or a fetus is accomplished by similar administration of the compound during the first third of the normal mammalian gestation period. Because the PGE compounds are potent antagonists of epinephrineinduced mobilization of free fatty acids, they are useful in experimental medicine for both in vitro and in vivo studies in mammals, including man, rabbits, and rats, intended to lead to the understanding, prevention, symptom alleviation, and cure of diseases involvinv abnormal lipid mobilization and high free fatty acid levels, e.g., diabetes mellitus, vascular diseases, and hyperthyroidism.  
  The PGE compounds promote and accelerate the growth or epidermal cells and keratin in animals, in-  
 cluding humans, and other animals. For that reason,  
 these compounds are useful to promote and accelerate healing of skin which has been damaged, for example, by burns, wounds; and abrasions, and after surgery. These compounds are also useful to promote and accelerate adherence and growth of skin autografts, especially small, deep (Davis) grafts which are intended to cover skinless areas by subsequent outward growth rather than initially, and to retard rejection of homografts.  
  For these purposes, these compounds are preferably administered topically at or near the site where cell growth and keratin formation is desired, advantageously as an aerosol liquid or micronized powder spray, as an isotonic aqueous solution in the case of wet dressings, or as a lotion, cream, or ointment in combination with the usual pharmaceutically acceptable diluents. In some instances, for-example, when there is substantial fluid loss as in the case of extensive burns or skin loss due to other causes, systemic administration is advantageous, for example, by intravenous injection or infusion, separate or in combination with the usual infusions of blood, plasma, or substitutes thereof. Alternative routes of administration are subcutaneous or intramuscular near the site, oral, sublingual, buccal, rectal, or vaginal. The exact dose depends on such factors as the route of administration, and the age, weight, and condition of the subject. To illustrate, a wet dressing for topical application to second and/or third degree burns of skin area 5 to 25 square centimeters would advantageously involve use of an isotonic aqueous solution containing 5 to 1000 ug/ml. of the PGE compound. Especially for topical use, these prostaglandins are useful in combination with antibiotics, for example, gentamycin, neomycin, polymyxin B, bacitracin, spectinomycin, and oxytetracycline, with other antibacterials, for example, mafenide hydrochloride, sulfadiazine, furazolium chloride, and nitrofurazone, and with corticold steroids, for example, hydrocortison&#39;e, prednisolone, methylprednisolone, and fluprednisolone, each of those being used in the combination at the usual concentration suitable for its use alone.  
  The presently described racemic PGEg, racemic PGF the enantiomorphic forms of PGE and PGF ,racemic PGE racemic PGF the enantiomorphic forms of PGE and PGF and the IS- epimers of all of the above each cause the biological responses described above for the POE- and PGF- compounds, respectively, and each of these compounds is accordingly useful for the above-described corresponding purposes, and is used for those purposes in the same manner as described above.  
 SUMMARY OF THE INVENTION It is the purpose of this invention to provide processes for the production of compounds useful in the preparation of prostaglandins commercially in substantial amount and at reasonable cost. It is a further purpose to provide processes for preparing certain intermediates in optically active forms. It is still a further purpose to provide a process for preparing racemic and optically active PGE and PGF their enantiomorphs, their IS-epimers, and their alkyl esters.  
  Thus, there is provided a process for preparing a racemic or optically active tricyclic lactone glycol of the formula CH-CH&#39;Y wherein Y is l-pentyl or 1-pent-2-ynyl, and indicates attachment of the moiety to&#39;the cyclopropane ring in exo or endo configuration, which comprises the steps of a. converting racemic or optically active bicyclo- [3. l .0]hex-2-ene-6-carboxaldehyde to a racemic or optically active acetal of the formula wherein R and R are alkyl of one to 4 carbon atoms, inclusive, or, when taken together,  
 wherein R R R R R and R are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or phenyl, with the proviso that not more than one of the Rs is phenyl and the total number of carbon atoms is from 2 to 10, inclusive; x is zero or one, and is as defined above;  
  b. transforming the racemic or optically active acetal to a racemic or optically active triicyclic dichloroke tone of the formula 10 wherein R R and are as defined above;  
  c. transforming the racemic or optically active tricyclic dichloroketone to a racemic or optically active tricyclic ketone of the formula or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein Y is l-pentyl or l-pent-2-ynyl, and indicates attachment of the moiety to the cyclopropane ring in exo or en&#39;do configuration and to the side chain in alpha or beta configuration, which comprises the steps of a. converting optically active or racemic bicyclo- [3.l.0]hex-2-ene-6-carboxaldehyde to an optically active acetal of the formula sor the mirror image thereof, .or a racemic compound of that formula and the mirror image thereof, wherein R and R are alkyl of one to 4 carbon atoms, inclusive,  
 or, when taken together,  
 wherein R R R R R and R are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or phenyl, with the &#39;proviso that not more than one of the Rs is phenyl and the total number of carbon atoms is from 2 to 10, inclusive; x is zero or one, and is as defined above;  
 b. transforming said optically active or racemic acetal to an optically active tricyclic mono or dihaloketone of the formula or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof. wherein R R and are as defined above, and wherein R is bromo or chloro, and R is hydrogen, bromo, or chloro;  
  c. transforming said optically active or racemic tricyclic mono or dihaloketone to an optically active tricyclic ketone of the formula K1 CH or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein R R and are as defined above;  
  d. oxidizing said optically active or racemic tricyclic ketone to an optically active tricyclic lactone acetal of the formula 0 a 5 l mi,  
 or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein R,, R and are as defined above;  
  e. hydrolyzing said optically active or racemic tricyclic lactone acetal to an optically active tricyclic lactone aldehyde of the formula or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein is as defined above;  
  f. converting said optically active or racemic tricyclic lactone aldehyde to an optically active tricyclic lactone alkene or alkenyne of the formula or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein Y and are as defined above; and  
  g. hydroxylating said optically active or racemic tricyclic lactone alkene or alkenyne to form said optically active or racemic tricyclic lactone glycol.  
  Reference to Chart A, herein, will make clear the transformation from bicyclic aldehyde 1 to tricyclic lactone glycol VIII by steps a-g, inclusive. Formulas I-X, inclusive, hereinafter referred to, are depicted in Chart A, wherein R, and R are alkyl of one to 4 carbon atoms, inclusive, or, when taken together,  
 wherein R R R R R and R are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or phenyl, with the proviso that not more than one of the Rs is phenyl and the total number of carbon atoms is from 2 to 10, inclusive; and x is zero or one; wherein R is alkyl of one to 5 carbon atoms, inclusive, R is bromo or chloro, and R is hydrogen, bromo, or chloro; wherein Y is lpentyl or l-pent-Z-ynyl; wherein W is l-pentyl, cis 1- pent-2-enyl, or l-pent-Z-ynyl; and wherein indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration, or attachment of the hydroxyl to the side chain in alpha or beta configuration.  
  In the formulas herein, the broken line attachments to a ring represent substituents in alpha configuration, i.e., below the plane of the paper. The wavy line indicates attachment of a group to a cyclopentane or lactone ring in alpha or beta configuration, or it indicates attachment to a cyclopropane ring in exo or endo configuration, or it indicates attachment to the C-l5 carbon of the prostamoic acid skeleton in a (S) or B (R) configuration. The formula of each intermediate as drawn herein is intended to represent the particular optical isomer which is transformed by the processes herein to an optically active prostaglandin having the natural configuration of prostaglandins obtained from mammalian tissues. The mirror image of each formula then represents a molecule of the enantiomorphic form of that intermediate. The expression racemic compound refers to a mixture of the optically active isomer which yields the natural configuration prostaglan din and the optically active isomer which is its enantiomorph.  
 The bicyclic aldehyde of Formula I in Chart A exists group, each of the exo and endo forms exists in two optically active (dor I-) forms, making in all four isomers. Each of those isomers separately or mixtures thereof undergo the reactions herein for producing prostaglandin intermediates and products. For racemic products the unresolved isomers are used. For the optically active prostaglandins, the aldehyde or subsequent intermediate isomers are resolved by my new process disclosed herein, and are used for preparing the optically active&#39;products. The preparation of the exo and endo aldehydes is discussed below under Preparations.  
  In carrying out step a, bicyclic aldehyde 1 is transformed to acetal II by methods known in the art. Thus, aldehyde I is reacted with either an alcohol of one to 4 carbon atoms, e.g., methanol, ethanol, propano l, or butanol in their isomeric forms, or mixture of such alcohols, or, preferably, a glycol having the formula R; 0 W Q 42L, mutt .&#39;&#34;J.J.ti..\ I  
  O2; 0; CHO Q H&#39; l (\J \OR: N eq l l l l l l 0 c 1 ..l&#39;ll.. I .lJ OR; OR Q, QM CH -cn cs0 R2 0R2 I V V VI 0 v 0 9 v Q Y 5 I x Q 1 CH=CH-Y NEH-(THAI 0H V l l VI l l 0 t i 0 a I .ii., Q I m-rR-w A OH 0.4 B 0 58 OSOQRQ IX X  a number of isomeric forms. With respect to the attacha, ment of the --CH0 group, it exists in two isomeric M g l l OH forms, exo and endo. Also, with respect to the position g of the cyclopentene double bond relative to the CH0 50 R R. x R;  
 wherein R R R R R and R are hydrogen, alkyl of one to 4 carbon atoms,,inclusive, or phenyl, with the proviso that not more than one of the Rs is phenyl and the total number of carbon atoms is from 2 to 10, inclusive; and x is zero or one. Examples of suitable glycols are ethylene glycol, 1,2-propanediol, 1,2-hexanediol, 1,3-butanediol, 2,3-pentanediol, 2,4-hexanediol, 3,4- octanediol, 3,5-nonanediol, 2,2-dimethyll ,3- propanediol, 3,3-dimethyl-2,4-heptanediol, 4-ethyl4- methyl-3,5-heptanediol, phenyl-1,2-ethanediol, and l-phenyll ,2-propanediol.  
  The step-a reaction is carried out under a variety of conditions using procedures generally known in the art. Thus, the reactants are dissolved in benzene and the mixture heated to remove the water formed azeotropically. To accelerate the reaction, there may be added an acid catalyst such as p-toluenesulfonic acid, trichloroacetic acid, zinc chloride, and the like. Alternatively,  
 the reactants, together with the acid catalyst and a water scavenger such as trimethyl orthoformate&#39;are warmed to 40-l00 C. in an inert solvent such as benzene, toluene, chloroform, or carbon tetrachloride.  
 . The ratio of the aldehyde to the glycol is preferably between 1:1 and 1:4.  
 1 cess of dichloroacetyl chloride in the presence ofa tertiary amine, e.g., triethylamine, tributylamide, pyridine, or l,4-diazabicyclo[2.2.2loctane, in a solvent such as n-hexane, cyclohexane, or mixture of. isomeric hexanes (Skellysolve B) at a temperature of from to 70 C. (See, for example, Corey et al., Tetrahedron Letters No. 4 pp. 307-310, 1970). Alternatively, the ketene Cl C=C=O is generated by adding a trichloroacyl halide to zinc dust suspended in the reaction vessel, omitting the tertiary amine.  
  ln carrying out step c, monoor dihaloketone III is reduced with a 2-to-5-fold excess of zinc dust over&#39;the stoichiometric ratio of Znz2 Cl in methanol, ethanol, ethylene, glycol, and the like, in the presence of acetic acid, ammonium chloride, sodium bicarbonate or sodium dihydrogen phosphate. Alternatively, the reac-. tion is carried-out with aluminum amalgam in a watercontaining solvent such as methanol-diethyl etherand the endo-trans olefins give similar mixtures of two threo glycol isomers-with trans and cis hydroxylation reagents, respectively. These various glycol mixtures are separated into individual isomers by silica gel chromatography. However, this separation is usually not w necessary, since each isomeric erythro glycol and each water, tetrahydrofuran-water, or dioxane-water,- at  
 about 050 C. I  
  In carrying out step d, tricyclic acetal. ketone IV is converted to a lactone by methods known in the art, for example by reaction with hydrogen peroxide, peracetiic acid, perbenzoic acid, m-chloroperbenzoic acid, and  
 the like, in the presence of a base such as alkali hydroxide, bicarbonate, or orthophosphate, using a preferred molar ratio of oxidizer to ketone of 111.  
  In carryingout step e, lactone acetal V to aldehyde V] by acid hydrolysis, known in the art,  
 using dilute mineral acids, acetic or formic acids, and  
 the like. Solvents such as acetone, dioxane, and,&#39;tetrahydrofuran are used.  
  In carrying out step f, aldehyde VI is transformed to the Formula-VII alkene or alkenyne, for example by means of an ylid as in the Wittig reaction. A l-h&#39;exyl halide or l-hex-3-ynyl halide, preferably the bromide, is used to prepare the Wittig reagent, e.g. he&#39;xyltriphenylphosphonium bromide or (hex-3-ynyl)triphenylphosphonium bromide.  
 In carrying out step g, the Formula-VII alkene or alkenyne is hydroxylated to glycol VIII by procedures known-in the art. See South African Patent No.  
 69/4809 issued July 3, 1970. In the hydroxylation of the respective endo or exo&#39;alkenes, various isomeric glycols are obtained depending on such factors as whether the CI-I=CH- moiety in VII is cis or trans,  
 and whether a cis or a trans hydroxylation reagent is used. Thus, endo-cis olefin&#39;gives a mixture of two isomeric erythro glycols of Formula VIII with a-cis&#39;hydroxylati&#39;on agent, e.g., osmium tetroxide. Similarly, the endo-trans olefin gives a similar mixture of the same two erythro glycols with a trans hydroxylation agent, e.g&#39;., hydrogen peroxide. The endo-cis olefins is converted passed by Formula VIII produced from the various isomeric olefins encompassed by Formula VII are all useful for these same purposes.  
  There is further provided by this invention a process for preparing an optically active bicyclic lactone diol of the formula XXXIX mi v &#39; Ol- 0H OH H XVI l XXV Oil X I tom \J/ &#39;\-:L//\\ da 0 H XXV I I or the mirror image thereof, or a racemic compound of 0 that formula and the mirror image thereof, by an ali kanesulfonyl group, R O S, wherein R is alkyl of one to 5 carbon atoms, inclusive, and indicates attachendo configuration and to the side chain in alpha or 3 beta configuration; and  
  b. mixing the compound formed in step a with water f at a temperature in the range of 0 to C. to form said optically active or racemic bicyclic lactone diol.  
 ilH  
 or the mirror image thereof, or a racemic compound 0 that formula and the mirror image thereof, wherein W ment of the moiety to the cyclopropane ring in exo or.  
 is l-pentyl, cis I-pent-Z-enyl, or l-pent-2-ynyl, and Glycol VIII is transformed by steps h and i into diol indicates attachment of the hydroxyl to the side chain X as ShOWn n C a t A. The procedures for forming the in alpha or beta configuration, which comprises th Formula-IX bis(alkanesulfonic acid) ester by replacing Steps f 0 the glycol hydrogen by an alkenesulfonyl group, and  
  a. replacing the glycol hydrogens of an optically acsubsequently hydrolyzing that ester to diol X are tive tricyclic lactone glycol of the formula known in the art (see South African patent cited immediately above).  
  0 In Chart A, there are differences in the terminal groups on the side chains of Formulas VII and VIII. In Formula VII, Y is limited to l-pentyl or l-pent-2-ynyl &#39;1&#39; whereas in Formula VIII, W includes l-pentyl, cis I- w pent-Z-enyl, or I-pent-Z-ynyl. The compounds of For- I Y mula VIII, IX, or X wherein W is cis l-pent-2-enyl are 1 obtained by reducing the -C I C- moiety of the l- 17 pent-2-ynyl group to cis Cl-I=CH before or after any of the steps h or i, ie, at any stage after the hydroxylation of the CH=CH moiety in step g. For that purpose, there are used any of the known reducing agents which reduce an acetylenic linkage to a cisethylenic linkage. Especially preferred for that purpose are dilmide or hydrogen and a catalyst, for example, palladium (5%) on barium sulfate, especially in the presence of pyridine. See Fieser et al., Reagents for Organic Synthesis,&#34; pp. 566-567, John Wiley &amp; Sons, Inc., New York, NY. (1967).  
  There is further provided a process for preparing an optically active bicyclic lactone diol of the formula or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein W is l-pentyl, cis lpent-2-enyl, or l-pent-2-ynyl, and indicates attachment of the hydroxyl to the side chain in alpha or beta configuration, which comprises starting with an optically active tricyclic lactone alkene or alkenyne of the formula or the mirror image thereof, or a racemic compound of that formula and the mirror image thereof, wherein Y is l-pentyl or l-pent-2-ynyl and indicates attachment of the moiety to theh cyclopropane ring in exo or endo configuration, and subjecting said alkene or alkenyne successively to the following reactions:  
 a. oxidation of the CH=CH moiety to an epoxy rmg,  
  b. hydrolysis of the resulting epoxide to a mixture of said bicyclic lactone diol and a tricyclic lactone glycol,  
  c. formolysis of said mixture to form a diformate of said bicyclic lactone diol, and  
  d. hydrolysis of said diformate to said bicyclic lactone diol, with the proviso that, W is cis l-pent-2-enyl, the C C- moiety is reduced to cis CH=CH be fore or after any of the steps b to d.  
  Reference to Chart B, herein, will make clear the transformation from the Formula-VII lactone alkene or alkenyne to diols X and X3 Formulas VII, X X B XXXVIII, XXXIX, and XL, hereinafter referred to, are depicted in Chart B, wherein E and M are both hydrogen or wherein one of E and M is hydrogen and the other is formyl, wherein Y is l-pentyl or l-pent-2- ynyl, wherein indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration, or attachment of OE and OM in threo or erythro configuration, or attachment to the side chain in a alpha or beta configuration, and wherein 0 f indicates attachment of the epoxide oxygen to the side chain in alpha or beta configuration.  
 The Formula-VII alkene or alkenyne, prepared by steps af of Chart A, is transformed to epoxide XXVlll by mixing reactant VII with a peroxy compound which is hydrogen peroxide or, preferably, an organic percarboxylic acid. Examples of useful organic percarboxylic acids for this purpose are performic acid, peracetic acid, perlauric acid, percamphoric acid, perbenzoic acid, m-chloroperbenzoic acid, and the like. Peracetic acid is especially preferred.  
  The peroxidation is advantageously carried out by mixing the reactant Vll with about one equivalent of the per acid or hydrogen peroxide, advantageously in a diluent, for example, chloroform. The reaction usually proceeds rapidly, and the formula-XXXVI epoxide is isolated by conventional methods, for example, evaporation of the reaction diluent and removal of the acid corresponding to the per acid if one is used. It is usually unnecessary to purify the oxide before using it in the next step. a  
  Two procedures are available for transforming epoxide XXXVIII to diol diformate XL. In one, the epoxide is hydrolyzed to a mixture of glycol XXXIX, wherein E and M are hydrogen, and diol X a [3 For this purpose, a solution of dilute formic acid in an Inert miscible solvent such as acetone, dimethyl sulfoxide, ethyl acetate, or tetrahydrofuran is used. Reaction temperatures of 20&#34; C. to C. may be employed, although about 25 C. in preferred. At lower temperatures, the desired mixture is produced inconveniently slowly. At higher temperatures, undesired side reactions reduce the yield of the desired mixture. Thereafter, the glycoldiol mixture is contacted with formic acid, preferably substantially 100 7r formic acid, at about 25 C. to form the diol formate. By substantially 100% foric acid&#34; is meant a purity of at least 99.5%.  
  In the other procedure, epoxide XXXVIII is subjected to formolysis directly. Preferably substantially 100% formic acid is used, at about 25 C. An inert solvent such as dichloromethane, benzene, or diethyl ether may be employed. 7  
  In either procedure, glycol monoformate XXXIX, wherein one of E and M is hydrogen and the other is formyl, is often present as an intermediate. It is ordinarily not isolated, but is converted to diol diformate XL in substantially 100% formic acid.  
  The diol diformate XL is obtained as a mixture of isomers in which the formyl group on the side chain are in the alpha and beta configurations. The mixture is converted directly to the diols X and X3 without separation. For this purpose, the diol diformates are contacted with a weak base such as an alkali metal carbonate, bicarbonate, or phosphate, preferably sodium or potassium bicarbonate, in a lower alkanol, for example methanol or ethanol. For this base hydrolysis, a temperature range of 10 C. to 50 C. is operable, preferably about 25 C. The product is a mixture containing the diols X a and X3 wherein the hydroxyl on the side chain is in the alpha and beta configuration. Separation of the alpha and beta diols is done by known procedures. Especially useful here is chromatography, for example on silica gel or alumina.  
 In Chart B, there aredifferences in the terminal groups on the side chains of Formulas VII, XXXVIII,  
 XXXIX, XL, X and X3 In Formula VII, Y is limited to l-pentyl or lpent-2-ynyl whereas in the other formulas W includes l-pentyl, cis --pent-2-enyl, or I- pent-Z-ynyl. Similarly to Chart A above, the compounds wherein W is cis l-pent-Z-enyl are obtained by reducing the -C E C moiety to cis CH=CHby methods known in the art at any stage after the epoxidation-of the CH=CH moiety of compound VII.  
  The formation of PGE or PGF from the formula- X lactone diol intermediate is done by the steps shown in Charts C and E known in the art. See E. J.-  
 Corey et al., J. Am. Chem. Soc. 9l,5675 (I969). The Formula-XI compound is within the scope of the Formula-X diol when W is n-C H The formation of P05 by carbonyl reduction of PGE is known in the art. For this reduction, use is made of any of the known ketonic carbonyl reducing agents which do not reduce ester or&#39;a cid groups or carbon-carbon double bonds when the latter is undesirable. Examples of those are the metal borohydrides especially sodium, potassium, and zinc borohydrides, lithium (tri-tertvbutoxy) and aluminum hydride, metal trialkoxy borohydrides, e.g.,  
 sodium trimethoxyborohydride, lithium borohydride, diisobutyl aluminum hydride, and when carbon-carbon double bond, especially cis, reduction is not a problem, the boranes, e.g., disiamylborane. As is known,&#39;this method gives a mixture of PGF and PGF fl which are readily separated by chromatography. The formation of PGA-; by acidic dehydration of PGE is known in the art. See, for example, Pike et al., Proc, Nobel Symposium II Stockholm I966), lnterscience Publishers, New York, p. 162 1957), and British Specification No. l,097,5 33. Alkanoic acids of 2 to 6 carbon atoms, inclusive, especially acetic acid, are preferred acids for this acidic dehydration. Dilute aqueous solutions of mineral acids, e.g., hydrochloric acid, especially in the presence of asolubilizing diluent, e.g., tetrahydrofuran.  
 are also useful as reagents for this acidic dehydration.  
 starting with an optically active glycol of the formula I on (EH or a racemic compound of that formula and the mirror image thereof, wherein indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration and to the side chain in a alpha or beta configuration, and subjecting said glycol successively to the following reactions:  
  a.&#39;replacement of the glycol hyd&#39;rogents by an alkanesulfonyl group, R O S, wherein R is alkyl of one to 5 carbon atoms, inclusive;  
  b. mixing with water at a temperaturelin the range of to 60 C. to form a bicyclic lactone diol of S and R configuration;  
 c. separation of said diols of S and Rf configuration; d. transformation to a bis(tetrahydropyranyl) ether; e. reduction of the lactone oxo group to&#39;a hydroxy 20 f. Wittig alkylation with a compound of the formula HaI-(CH COOH wherein Hal is bromo or chloro;  
  g. oxidation of the 9-hydroxy to 0x0; and h. transformation of the two tetrahydropyranyloxy groups to hydroxy groups;  
 -with the proviso that, before or after any of the steps a to h, the C E C moiety is reduced to cis Reference to Charts A and D, herein, will make clear 10 the transformation from bicyclic aldehyde I to PGE ent-PGE dl-PGE or their IS-epimers. In Chart D, Z is cis l-pent-Z-enyl or l-pent-Z-ynyl, and and THP are as defined above. A key intermediate for this sequence is the racemic or optically active lactone aldehyde-VI. The Formula-VI compound is prepared from racemic bicyclic aldehyde I by steps ae of Chart A and thereafter resolved in an optically active form by the method disclosed hereinafter via the oxazolidine of Example 15. Optionally, the Formula-I aldehyde is resolved as disclosed hereinafter in Example 13, and thereafter converted to the optically active Formula-VI compound.  
  In carrying out step f of Chart A, the wittig reaction is employed, using a l-hex-2-ynyl chloride, bromide, or iodide, preferably bromide, to prepare the necessary Wittig reagent by processes known in the art.  
 In carrying out steps g through i of Chart A, the pro-.  
 cedures for hydroxylating the Formula-VII alkenyne wherein Y is l-pent-2-ynyl, forming the Formula-IX bis-(alkanesulfonic acid) ester, and hydrolyzing that ester to the Formula-X lactone diol are generally known in the art. See South African Patent No. 69/4809 issued July 3,1970. The Formula-X lactone diol, which contains both a and B epimers as produced, yields the final product as a mixture of PGE and its 15- epimer. It is preferable that the diol a and B epimers be separated rather than the final product eplmers. Silica gel chromatography is employed for this purpose. The Formula-X B-epimer then leads to the dl-l5B-PGE In converting glycol VIII, wherein W is l-pent-Z-ynyl, to the Formula-XXII product, the C I C moiety is reduced to cis CH=CI-I at any stage. Thus, glycol VII is optionally reduced before replacing the glycol hydrogens which an alkane-sulfonyl group. or any of the Formula-IX, -X, -XVIII, -XIX, -XX, or -XXI intermediate is optionally reduced. Reducing reagents, catalysts, and conditions are used which do not substantially reduce -CH=CH. A suitable method is to hydrogenate over a Lindlar catalysts, i.e. 5% palladium- .on-barium sulfate catalyst, in the presence of eqinoline. Mathanol or like inert solvent or diluent is used and the pressure is low, advantageously slightly above atmospheric and ordinarily not above about two atmospheres. The resulting prooducts are isolated by silica gel chromatography.  
  The formation of PGE from the Formula-XVII diol intermediate by the steps of Chart D, other than the reduction step above-described, generally follows procedures known in the art and discussed above under the formation of PGE There is further provided a process for preparing PGF di-PGF or their l 5-epimers, in which glycol VIII, wherein W is l-pent-Z-ynyl, is transformed to diol XVII, wherein Z is cis l-pent-Z-enyl or l-pent-2- ynyl, and thence to the Formula-XXVI products, as depicted by the steps of Chart F. Accordingly, diol XVII is reduced to lactol XXV which is then alkylated by a Wittig reaction. As in the process for PGE the C I C- moiety is reduced to &#39;cis CH=CH at any stage between the glycol and the end-product. As in the process for PGE the optical isomers of the intermediates yield the corresponding PGF or ent- PGF the racemic intermediates yield racemic pGF the optically active orand B-config uration intermediates yield the corresponding PGF ent- PGF or their IS-epimers.  
  The formation of racemic and optically active PGF from racemic and optically active pGE generally follows procedures known in the art, e.g., by carbonyl reduction with borohydride, discussed above under the formation of PGF The formation of racemic and optically active PGA from racemic and optically active PGE likewise follows procedures known in the art, e.g., by acidic dehydration, discussed above under the formation of PGA-;.  
  There is further provided a process for resolving a racemlc mixture of an oxo compound of the formula 9% ,4. Q QIV or Q,  
 CHO CH and of the mirror image thereof, wherein R and R are alkyl of one to 4 carbon atoms, inclusive, or, when taken together,  
  H3 lig l iv &#34;i ll l -ii e wherein R R R R and P are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or phenyl, with the proviso that not more than one of the R&#39;s is phenyl and the totalv number of carbon atoms is from 2 to 10, inclusive; .r is zero or one, and indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration, which comprises the steps of a. converting the oxo compound by reaction with an optically active ephedrine to a mixture of oxazolidine diastereomers,  
  b. separating at least one oxazolidine diastereomer from said mixture,  
  0. hydrolizing said oxazolidine to free the optically active oxo compound, and  
 d. recovering said optically active oxo compound.  
  In carrying out the resolution of the Formula-l bicyclic aldehyde, there is prepared an oxazolidine by reaction of the aldehyde with an optically active sphedrine,  
 e.g. dor l-epeorine, or dor l-pseudoephedrine. Approximately equilmolar quantities of the-reactants are employed in a solvent such as benzene, isopropyl ether, or dichloro methene. Although the reaction proceeds smoothly over a wide range in temperature, e.g., 10-80 C., it is preferred that it be done in the range 20 to 30 C. to minimize side reactions. With the Formula-l compound, it occurs quickly, within minutes, whereupon the solvent is removed, preferably under vacuum. The product consists of the diastereomers of the aldehyde-ephedrine product, i.e.&#39; the oxazolidines. At least one of the diastereomers is separated by methods known in the art, including crystallization and chromatography. In this instance, crystallization is used as the preferred method. Repeated recrystallization of the thus-obtained solid oxazolidine from a suitable solvent, e.g., isopropyl ether, yields one of the diastereomers in substantially pure form. The oxazolidine is then hydrolyzed by procedures known in the art to release the aldehyde. However, I have found silica gel wet with water surprisingly effective, using the silica gel in a column, with the further beneficial effect that the column acts as a means of separating the ephedrine from the aldehyde. The eluted fractions are then evaporated to yield the desired resolved Formula-l aldehyde.  
  The mother liquor from the recrystallized diastereomer contains the optical isomer having opposite configuration. A preferred method for isolating this second diastereomer, however, is to prepare the oxazolidine of .the racemic aldehyde using ephedrine of the opposite ful intermediates in these processes directed toward prostaglandins, viz, bicyclic aldehyde I in its optically active forms; acetal ll; mono or dihaloketone lll; ketone lV; lactone acetol V; lactone aldehyde Vl; the Formula-VII lactone heptene or heptenyne; lactone glycol VI and monoformate XXXIX of the generic formula wherein E and M are both hydrogen, or wherein one of E and M is hydrogen and the outer is formyl, and wherein W is l-pentyl, cis l&#39;pent-2-enyl, or l-pent-Z ynyl; the lactone bis(alkanesulfonate) [X of the formula wherein R is alkyl of one to 5 carbon atoms, inclusive, and W is as defined above; epoxide XXXVIII of the formula f ocu-cH-w wherein W is as defined above, and wherein t t, G y W I OCHO OCHO wherein W is as defined above; lactone diol XI represented by the mirror image of the formula wherein Z is cis l-pent-2-enyl or l-pent-2-ynyl; tetrahydropyranyl lactone XVIII of the formula O&#39;THP OTHP wherein THP is tetrahydropyranyl and Z is as defined above; tetrahydropyranyl lactol XIX of the formula cm 8&#39;5 CL... Z r o&#39;m P THP wherein TI-IP and Z are as defined above; and an oxazolidine of bicyclic aldehyde I, ketone IV, or lactone aldehyde VI with an optically active ephedrine. In these compounds indicates attachment to the cyclopropane ring in exo or endo configuration and to the sidechain in 01(5) or B (R) configuration. There are also provided the enantiomorphs and the racemic mixtures of the above compounds.  
 DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention is further illustrated by, but not limited to, the following examples.  
 All temperatures are in degrees Centigrade.  
  Infrared absorption spectra are recorded on a Perkin- Elmer model 421 infrared spectrophotometer. Except when specified otherwise, undiluted (neat) samples are used.  
  The NMR spectra are recorded on a Varian A-6O spectrophotometer in deuterochloroform solution with tetramethylsilane as an internal standard (downfield).  
  Circular dichroism curves are recorded on a Cary 60 recording spectropolarimeter.  
 The collection of chromatographic eluate fractions starts when the eluent front reaches the bottom of the column.  
 Brine, herein, refers to an aqueous saturated sodium chloride solution.  
 Preparation 1 Endo-bicyclo[3. l .0]hex-2-ene-6-carboxaldehyde (Formula I: is endo).  
  To a rapidly stirred suspension of anhydrous sodium carbonate (318 g.) in a solution of bicyclo[2.2.l lhepta-2,5-diene (223.5 g.) in dichloromethane (1950 ml.) is added 177 ml. of 25.6% peracetic acid containing 6 g. of sodium acetate. The addition time is about 45 min., and the reaction temperature is 20-26 C. The mixture is stirred for an additional 2 hrs. The reaction mixture is filtered and the filter cake washed with dichloromethane. The filtrate and washings are concentrated under vacuum. About 81 g. of the resulting liquid is stirred with 5 ml. of acetic acid in 200 ml. of dichloromethane for 5.5 hrs., then concentrated and distilled. The fraction boiling at 69 73 C./30 mm. represents the desired Formula-I aldehyde, 73 g. NMR peaks at 5.9- and 9.3 (doublet) 6.  
  The various Formula-I-to-IX intermediate, hereinafter, exist in exo as well as endo forms. A preferred route to the exo form of the Formula-I bicyclic aldehyde is by the steps shown in Chart G, using methods known in the art. See South African Patent 69/4809 issued July 3, l970. ln Formulas XXVII to XXXVII, the attachment to the cyclopropane ring by a straight line extended downward at an angle to the right indicates the exo configuration. Thus,- diazoacetic acid is added.  
 to a double bond of cyclopentadiene to give an exoendo mixture of the Formula-XXVIII -bicyclo[3.l.0]- hexene substituted at the 6-position with a carboxyl. The exo-endo mixture is treatedwith abase to isomerize the endo isomer in the mixture to more of the exo isomer. Next the carboxyl group at 6 is transformed to an alcohol group and thence to the exo aldehyde of the Fon&#39;nula XXX.  
 Example 1 dl Endo-bicyclo[3.1.0]hex-2-ene-6-carboxaldehyde Acetal of Ethylene Glycol (Formula 11: R, and R taken together are -CH CH and is endo).  
  Refer to Chart A solution of Formula-1 endo-bicyclo- [3.1.0]hex-2-ene-6-carboxeldehyde (216 g., Preparation 1 ethylene glycol 150 g.). and p-toluenesulfonic acid (0.5 g) in benzene (1 l.) is heated under reflux. The azeotropically distilled water (29 ml. after hrs.) is collected in a Dean-Stark trap. The reaction mixture is cooled, treated with sodium carbonate (0.3 g.). and distilled at reduced pressure. The fraction collected at 5560 C./34 mm. is partitioned between ether and water. The ether layer is extracted with water, dried over anhydrous magnesium sulfate, and concentrated to the Formula-ll bicyclic acetal. a light tan oil (70 g.); NMR peaks at 1.1, 1.6-2.9, 3.5-4.2, 4.42, and 5.3-6.0 8.  
  Following the procedures of Example 1 but using the exo Formula-l (XXX) compound, there is obtained the corresponding cmm c 3 xxvn Q xxvm coon XXIX CHQOH xxx CHO exo Formula-ll acetal.  
  Following the procedures of Example 1 but using either the endo or exo form of the Formula-l aldehyde and substituting for the ethylene glycol one of the following glycols: 1,2-propanediol, 1,2-hexanediol, 1,3- butanediol, 2,3-pentanediol, 2,4-hexanediol, 3,4- octanediol, 3,5-nonanediol, 2,2-dimethyll ,3- propanediol, 3,3-dimethyl-2,4-heptanediol, 4-ethyl-4- methyl-3,5-heptanediol, phenyl-1,2-ethanediol and l-phenyl-1,2-propanediol. there are obtained the corresponding Formula-ll acetals.  
  Following the procedures of Example 1 but using either the endo or exo form of the Formula-I adehyde and substituting for the ethylene glycol one of the following alcohols: methanol, ethanol. l-propanol. or 1- butanol, there are obtained the corresponding formula- II acetals.  
 EXAMPLE 2 diTricyclic Dichloroketone (Formula Ill; R and R taken together are -CH CH and is endo).  
  Refer to Chart A. A solution of the Formula-II bicyclic acetal of Example 1. (56 g.) and triethylamine g.) in 300 ml. of isomeric hexanes (Skellysolve B) is heated at reflux, with stirring, and treated dropwise with dichloroacetyl chloride g.) in Skellysolve B over a 3-hour period. The mixture is cooled and filtered to remove solids. The filtrate and combined Skellysolve B washes of the filtered solid is washed with water, 5% aqueous sodium bicarbonate, and brine, dried over anhydrous sodium sulfate and concentrated to the title compound, a dark brown oil (91 g.). An additional quantity (13 g.) is recovered from the filter cake and aqueous washes. Alternatively, the triethylamine is added to a solution of the bicyclic acetal and the dichloroacetyl chloride, or the triethylamine and the di- EXAMPLE 3 diTricyclic Ketone (Formula lV: R and R are methyl and is endo).  
  A solution of the Formula-III dichloroketone of Example 2 104 g.) in dry methanol (1 l.) is treated with ammonium chloride 100 g.) and small portions of zinc dust. The temperature is allowed to rise to 60 C. After 200 g. of zinc have been added, the mixture is heated under reflux for an additional 80 min. The mixture is cooled, the solids filtered off, and the filtrate concentrated. The residue is treated with dichloromethane and 5% aqueous sodium bicarbonate and the mixture is filtered. The dichloromethane layer is washed with 5% aqueous sodium bicarbonate and water, dried, and concentrated to the title compound, a dark brown oil (56 g.); infra-red absorption at 1760 cml.  
  Following the procedures of Example 3 but using the exo Formula-lllcompound, there is obtained the correspondingexo Formula-1V tricyclic ketone.  
  Following the procedures of Example 3 but using the Formula-111 compounds disclosed following Example 2, there are obtained the corresponding Formula-1V compounds.  
 EXAMPLE 4 diTricyclic Lactone acetal (Formula V: R and R are methyl and is endo), and Tricyclic Lactone Aldehyde (Formula V1 is endo) Refer to Chart A. A solution of the Formula-1V product of Example 3 (56 g.) in dichloromethane (400 ml.) is treated with potassium bicarbonate 40 g.) and cooled to 10 C. A solution of meta-chloroperbenzoic acid (55 g. of 85%) in dichloromethane (600 ml.) is added over 40min. The mixture is stirred at 10 C. for 1 hr., then warmed to reflux for 40 minqThe mixture is cooled and filtered, and the filtrate is wased with 5% aqueous sodium bicarbonate-sodiumthiosulfate, and then water. The dichloromethane layer is&#39;dried over anhydrous sodium sulfate, and concentrated to the Formula-V acetal (61 g.). A portion (58 g.) is chromatographed on 2 kg. of silica gel packed in ethyl acetate-&#39; tion (24.9 g.) shown by NMR to be a mixture of di- 1 methyl acetal (V) and aldehyde (VI). A portion-(22.6  
 g.) of the mixture is dissolved in 100 ml. of (60-40) formic acid-water and allowed to stand 1 hr. at 25C.  
 The solution is then concentrated under vacuum and the residue taken up in dichloromethane. The dichloromethane solution is washed with 5% aqueous ,sodium&#39; bicarbonate and water, dried over sodium sulfate, and concentrated to a brown oil (17.5 g.) which crystallizes on seeding. Trituration of the crystals with benzene leaves crystals of the Formula-VI aldehyde (9.9 g.). An analytical m.p. 72-74 C (corn); infrared absorption peaks at 2740, 1755, 1710, 1695, 1195, 1165, 1020, 955, and 910, cm 1;NMR peaks at 1.8-3.4, 5.0-5.4, and 9.92 8.  
 , Following the procedures of Example 4 but using the exo Formula-IV lactone acetal compound, there is obtained the corresponding exo Formula-V lactone acetal. 1  
  Likewise, following the procedures of Example 4 using the exo Formula-V compound, there is obtained the corresponding exo Formula-V1 lactone aldehyde.  
  Following the procedures of Example 4 but using the Formula-IV compounds disclosed following Example 3, there are obtained the corresponding Formula-V compounds, and, thence, the corresponding Formula- Vl lactone aldehydes.  
 XXVI]- EXAMPLE 5 diTricyclic lactone Heptene (Formula Vll: Y is l-pentyl and is endo).  
  Refer to Chart A. A suspension of n-hexyltriphenylphosphine bromide (6.6 g.) in 20 ml. of benzene is stirred under nitrogen and to it is added 10 ml. of 1.6 m. n-butyllithium in n-hexane. After 10 min. a benzene solution of the Formula-VI tricyclic aldehyde (1.66 g.) of Example 4 is added dropwise over 15 min. and the reaction mixture is heated at 65-70 C. for 2.5 hrs.  
 The mixture is cooled, the solids are filtered off and washed with benzene, and the combined filtrate and washes are extracted with dilute hydrochloric acid and water. The solution is dried over sodium sulfate and concentrated under vacuum to an oil (3.17 g.). The crude Formula-V11 product is chromatographed on 400 g. of a silica gel packed with (30-70) ethyl acetatecyclohexane and eluted with the same mixture. Fractions of 20 m1. volume are collected. Fractions 47-50 are found to contain 0.8 g. of the desired Formula-V11 tricyclic lactone heptene; NMR peaks at 0.6-3.0, 4.4- 5.1, and 5.4 6. To minimize side reactions, it is preferred that the ,Wittig reagent prepared from the phosphonium bromide and n-butyllithium be filtered to remove lithium bromide, and that the resultant solution be added to the benzene solution of the Formula-V1 tri-- cyclic aldehyde in equivalent proportions.  
  Following the procedures of Example 5 but using the exo Formula-VI compound, there is obtained the corresponding exo Formula-VII lactone heptene. A preferred source of the exo form of the Formula-V1 tricyclic lactone aldehyde is by the steps shown in Chart H.  
 -.Therein R is alkyl of one to 4 carbon atoms. Thus,  
  step C of Chart A; the resulting Formula-XXXlll tricyclic ketone is converted to a lactone ester as in step d of Chart A; the lactone is saponified, then acidified, to  
 I yield the Formula-XXXV compound with a carboxyl group at the 6-position; then the carboxyl group is transformed to an alcohol group and finally to the exo aldehyde of Formula XXXVI];  
 EXAMPLE 6 diTricyclic Glycols (Formula Vlll: W is l-pentyl and is endo).  
  Refer to Chart A. Procedure A. A solution of the Formula-VII tricyclic QEAELE.  
  i-i COOR XXXl  Continued COOR COOH XXXlll XXXV \(XXVII XXXVI latone heptene of Example 5 (0.8 g.) in ml. of benzene is treated with osmium tetroxide 1.0 g.) in ml. of benzene. After standing 24 hrs., the mixture is treated with hydrogen sulfide for min., then filtered to remove a black solid. Thefiltrate is evaporated to an oil (393 mg). An additional quantity of oil (441 mg.) is recovered by suspending the black solid in ethyl acetate and again treating with hydrogen sulfide. The oil is chromatographed on 100 g. of silica gel packed and eluted with (-60) acetone-dichloromethane. Fractions of 20 ml. volume are collected. Two erythro glycols of Formula VIII are recovered,-one more polar (slower-moving on the column) then the other. The faster-moving glycol, 0.3 g., is found in fractions 20-30; the slower-moving one, 0.28 g.. in fractions 31-40.  
  Procedure B. A mixture of 7 ml. of N- methylmorpholine oxide-hydrogen peroxide complex (see Fieser et al., Reagents for Organic Syntheses p. 690, John Wiley and Sons, lnc., New York, N.Y. (1967)), 8 ml. of T&#39;HF. 14 ml. of tert-butanol. and ssmium tetroxide (2 mg.) in 2ml. of tert-butanol is cooled to about 15 C.  
  A solution of the Formula-VII tricyclic lactone heptene of Example 5 (3.95 g.) in 12 ml. of THF and 12 ml. tertbutanol is then added slowly over a period of 2 hrs. at a temperature of l520 C. The mixture is stirred for an additional 2 hrs., and to it is added a slurry of filter aid (for example magnesium silicate, 0.8 g.) in l4 ml. of water containing sodium thiosulfate (0.4 g.), and the solids removed by filtration. The filtrate is concentrated under reduced pressure to an oil.  
 Water (200 ml.) is added and the oil-water mixture is extracted with several portions of dichloromethane. The dichloromethane solution is dried over magnesium sulfate and then concentrated under reduced pressure to a mixture containing the title products.  
  Following the procedures of Example 6A and 6B but using the exo Formula-VII compound, there are obtained the corresponding exo Formula-VII tricyclic glycols.  
 EXAMPLE 7 diBicyclic lactone Bismesylate (Formula IX: R is methyl, W is l-pentyl, and is endo), and Bicyclic Lactone Diol (Formula X: W is l-pentyl and indicates the a configuration).  
 Refer to Chart A. The slower moving formula-VIII erthro glycol from Example 6 (277 mg.) is dissolved in 5 ml. of pyridine, cooled to 0 C. under nitrogen, and treated with methanesulfonylchloride (0.89 g.). The  
 mixture is stored at 0 C. for 20 hrs., ice water (0.6 ml.) t  
 is added and the mixture stirred an additional 20 min. Then the mixture is poured into dichloromethane and washed with ice-cold l N. hydrochloric acid, ice-cold 5% sodium bicarbonate solution, and ice water. The solution is dried and concentrated under vacuum to an oil etone. The solution is diluted with water and extracted with dichlorommethane. The dichloromethane solution is washed with sodium bicarbonate solution and brine, dried, and concentrated under vacuum to an oil (200 mg), consisting of the Formula-X product.  
  The FormulaX compound is obtained as a mixture of isomers in the a and [3 configuration. They are separated by silica gel chromatography and are used separately, e.g. in preparing the Formula-X11 bis(tetrahydropyranyl) ether. The undesired Formula-X isomer is recycled to isomerize it to a mixture of the a and ,8 forms. For the isomerization, the lS-hydroxyl is oxidized to a -keto with selective oxident, e.g., 2,3- dichloro-5 ,6-dicyano-1 ,4-benzoquinone, activated manganese dioxide. or nickel peroxide (see Fieser et al., Reagents for Organic Syntheses, John Wiley and Sons, lnc., New York, N.Y., pp 215, 637, and 731). Thereafter, the l5-keto compound is reduced with zinc borohydride, by methods known in the art, to a mixture of the a and {3 isomers, which are then separated by silica gel chromatography.  
  Following the procedure of Example 7, The fastermoving glycol is transformed to the same Formula-X product as above.  
  Following the procedures of Example 7 but using the exo Formu1a Vl11 compound, there is obtained the corresponding exo Formula-1X bismesylate. This exo bismesylate is transformed to the Formula-X lactone diol by the procedures of example 7 used for the endo compound.  
  The Formula-X latone diol wherein W is l-pentyl is transformed to dl-PGE and dl-PGF and their alkyl esters using methods generally known in the art, e.g., following the steps of Chart C for dl-PGE and Chart E for dl-PGF EXAMPLE 8 diEndo-bicyclo[3. l .0]hex-2-ene --carboxaldehyde Acetal of 2,2-dimethyl-1 ,3-propanediol (Formula 11: R  
 and R taken together are CH C(CH CH and is endo).  
  Refer to Chart A. A solution of Formula-l endobicyclo[3.1.0]hex-2-ene-6-carboxaldehyde (48.6 g. 2,2-dimethyl-1,3-propanediol (140.4 g.), and oxalic acid (0.45 g.) in benzene (0.91.) is heated under reflux for 4 hrs. The azeotropically distilled water is removed in a water separator. The reaction mixture is cooled, washed with 5% sodium bicarbonate solution and water. The benzene solution is dried over sodium sulfate, concentrated to an oil (93 g.), and distilled at reduced pressure. The fraction boiling at 88-95 C/0.5 mm. is the desired title compound, 57.2 g., m.p. 53-55 C.; NMR peaks at 0.66, 1.2, 3.42, 3.93, and 5.6 8; infrared absorption at 1595, 1110, 1015, 1005, 990, 965, 915 and 745 cm&#34;.  
  Following the procedures of Example 8 but using the exo Formula-1 compound, there is obtained the corresponding exo Formula-ll acetal.  
 EXAMPLE 9 ple 2, the Formula-11 compound of Example 8 is transformed to the title compound, m.p. 97100 C., NMR  
 peaks at 0.75. 1.24, 2.43 (multiplet), 3.42, 3.68, and 3.96 (doublet) 0; infrared absorption at 3040, 1810, 1115, 1020, 1000, 980, 845, and 740 cm.  
 EXAMPLE 10 d1 Tricyclic Ketone (Formula IV: R and R taken together are -Cl-l C(Cl-l )2CH and is endo).  
 Refer to Chart A. Following the procedure of Example 3, the Formula-111 dichloroketone of Example 9 is transformed to the title compound, an oil; NMR peaks at 0.75, 1.25, 3.0 (multiplet) and 4.0 (doublet) 8; infrared absorption at 1770 cm.  
  Following the procedures of Example 3 and 10 but using the corresponding exo Formula-III compound, there is obtained the corresponding exo Formula-1V tricyclic ketone.  
  EXAMPLE 10A dl- Tricyclic Lectone Acetal (Formula V: R, and R taken together are -Cl-l -C(Cl-l CH and is endo) and Tricyclic Lactone Aldehyde (Formula Vl: is endo).  
  Refer to Chart A. Tricyclic ketone IV (Example 1O, 12 g.) together with potassium bicarbonate (6.1 g.) in ml. of dichloromethane is cooled to about 10 C. Metachloroperbenzoic acid (12.3 g. of 85%) is added &#39;portionwise at such a rate that the reaction temperature is kept below 30 C. Thereafter the mixture is stirred for 1 hr. and to it is added ml. of 5% aque-,  
 ous sodium bicarbonate solution containing 9 g. of sodium thiosulfate. The dichloromethane layer is dried over sodium sulfate and concentrated under reduced pressure. The oily residue contains the Formula-V lactone acetal: NMR peaks at 0.75, 1.23, 3.5 (quartet), 3.9 (doublet) and 4.8 (quartet) 8; infrared absorption at 1760 cm. 1  
  Lactone acetal V (about 4.4 g.) in 60 ml. of 88% formic acid is left standing at-50 C. for 1 hour. The solution is then cooled, diluted with 60 ml. of 1 N. sodium hydroxide saturated with sodium chloride, and extracted with dichloromethane. The combined extracts are washed with 10% sodium carbonate, dried over sodium sulfate, and concentrated under reduced pressure. The product crystallizes onv standing, yielding the Formula-V1 lactone aldehyde: m.p. 6973 C., NMR peaks at 5.2 (multiplet) and 10.0 (doublet) 8, and infrared absorption at 1755 cm&#34;.  
  Following the procedures of Example 10A, the corresponding exo Formula-IV tricyclic ketone yields the corresponding Formula-V and -V1 compounds.  
 EXAMPLE l1 .dl-PGE dl-15-epi-PGE and their Alkyl Esters (Formula XXll of Chart D: indicates the 150: or 158 configuration).  
 -X compounds wherein W is lpent-2-ynyl and is endo for the moiety on the cyclopropane ring, and represents either the a or B configuration for the hydroxyl group on the side-chain. The Formula-X octenyne diol is obtained as a mixture of isomers in the a and B configuration. They are separated by silica gel chromatography and are used in preparing the Formula-XVII compounds. The undesired Formula-X isomer is recycled and isomerized using the procedures of Example 7. The (Jr-configuration Formula-X octenyne diol wherein W is l-pent-Z-ynyl is reduced to the Formula- XVII octadiene diol wherein Z is l-pent-2-enyl by reducing the C i C- moiety to cis CH=CH by hydrogenation over Lindlar catalyst as follows. To a solution of the Formula-X compound (20 mg.) in methanol (2 ml.) is added 5 mg. of 5% palladium-on-barium sulfate and 2 drops of synthetic quinoline. The mixture is stirred at about 25 C. and atmospheric pressure. The reaction is terminated when one equivalent of hydrogen is absorbed. The mixture is filtered and the filtrate concentrated under vacuum. Ethyl acetate is added and the solution is chromatographed on silica gel impregnated with silver nitrate. The column is developed with isomeric hexanes (Skellysolve B) containing increasing amounts of ethyl acetate. Those fractions containing the desired octadiene diol are combined and concentrated to yield the Formula-XVII intermediate.  
  Following the steps of Chart D, the Formula-XVII compound, wherein Z is l-pent-2 enyl and represents the a configuration, is transformed to PGE using methods generally known in the art. Thus, the Formula-XVII diol is converted to the Formula-XVIII bias(tetrahydropyranyl) ether; the oxo group of the lactone is reduced to form the Formula-XIX lactol; the Formula-XX compound is formed by a Wittig reaction using m-chloro or m-bromopentanoic acid; the Formula-XX 9-hydroxygroup is oxidized to the 9-keto group of the Formula-XXI intermediate; and, finally, the protective tetrahydropyranyl groups are removed by hydrolysis to yield the desired Formula-XXII dl- PGE Following the procedures of Example 1 l, but substituting the exo Formula-I aldehyde for the endo aldehyde, there are obtained the Formula-VI, -VII, -VIII and -IX exo compounds which are converted to the Formula-X lactone diol, and thence to dl-PGE Following the procedures of Example 1 l for dl-PGE but substituting the 155 (R)-configuration Formula-X octenyne diol for the S-configuration compound, there are formed any of the Formula-XVII-to-XXI intermediates wherein indicates the B configuration, and thence dl&#39;l SB-PGE of Formula-XXII wherein indicates the B configuration.  
  Although Example 1 1 illustrates one embodiment of the process for preparing PGE wherein the -C- C-moiety of the Formula-X octenyne diol is reduced to cis --CH=CHimmediately before forming the cis(tetrahydropyranyl)ether, it is within the scope of this invention as shown in Charts A and D to carry out that reduction of--C E C to cis -CH=CH at any stage between the Formula-VIII glycol and the final dl-PGE or dl-l5B-PGE Thus, the Formula-VIII compound wherein W is lpent-2ynyl and indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration, is subjected successively to the following reactions a. replacement of the glycol hydrogens by an alkanesulfonyl group, R O S, wherein R is alkyl of one to 5 carbon atoms, inclusive;  
  b. mixing with water at a temperature in the range of 0 to C. to form a bicyclic lactone diol;  
 0. separation of the diols of a (S) and B(R) configuration;  
 d. transformation to a bis(tetrahydropyranyl) ether;  
 e. reduction of the lactone oxo group to a hydroxy group;  
  f. Wittig alkylation with a compound of the formula Hal-(CH COOI-I wherein Hal is bromo or chloro;  
 g. oxidation of the 9-hydroxy to 0x0; and  
  h. transformation of the two tetrahydropyranyloxy group to hydroxy groups; with the proviso that, before or after any of the steps a to h, the -C a C- moiety is reduced to cis CH=CH, thereby forming dl-PGE or dl-15,8- PGE. By these procedures, there are formed the intermediates of Formulas VIII, IX, and X, wherein X is either cis 1-pen -2-enyl or l-pent-Z-ynyl; and the intermediates of Formulas XVIII, XIX, XX, and XXI, wherein Z is either cis l-pent-2-enyl or l-pent-2-ynyl.  
 EXAMPLE l2 dl-PGF and dI-ISepi-PGF Esters (Formula XXVI of Chart E: indicates the 15a (S) or 153 (R) configuration).  
  Refer to Chart E. Following the procedures of Example l 1, there is prepared the oz-configuration Formula- XVII octadiene diol. This diol is transformed to PGF by the steps shown in Chart E wherein indicates the a configuration, using methods known in the art. Thus, the Formula-XVII diol is converted to the Formula-XXV lactol by reducing the 0x0 group of the lactone; and the Formula-XXV compound is converted to dl-PGF (Formula XXVI wherein indicates the S configuration) by a Wittig reaction using w-chloro-or w-bromo-pentanoic acid.  
  Following the procedures of Example 12, but substituting the B-configuration Formula-XVII octadiene diol for the a-configuration Formula-XVII octadiene diol, there is obtained dl-lSB-PGF (Formula XXVI wherein indicates the ,Bconfiguration).  
  Although Example 12 illustrates one embodiment of the process for preparing PGF wherein the C E C- moiety of the Formula-X octenyne diol is reduced to cis CH=Cl-I immediately before reducing the lactone oxo group to a hydroxy group, it is within the scope of this invention as shown in Charts A and F to carry out the reduction of C i C- to cis CI-I=CI-I- at any stage between the Formula-VIII glycol and the final dl-PGF and dl-l5B-PGF Thus, the Formual-VIII compound wherein W is lpent-Z-ynyl and indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration is subjected successively to the following reactions:  
  a. replacement of the glycol hydrogens by an alkanesulfonyl group, R O S, wherein R is alkyl of one to 5 carbon atoms, inclusive;  
  b. mixing with water at a temperature in the range of 0 to 60 C. to form a bicyclic lactone diol;  
 0. separation of the diols of a and ,3 configuration;  
  d. reduction of the lactone oxo group to a hydroxy group; and  
  e. Wittig alkylation with a compound of the formula I-Ial(CI-I -COOH wherein Hal is bromo or chloro;  
 with the proviso that, before or after any of the steps a to e, the C Q! C- moiety is reduced to cis f-CH=CH, thereby forming dl-PGF g or dl-lSB- 2-enyl or 1-pent-2-ynyl.  
 EXAMPLE 13 Resolution of Endo-bicyclo[3. 1.0]hex-2-ene-6-carboxaldehyde (Formula 1: is endo).  
  A. Formula-I endo-bicyclo[3.1.0]hex-2-ene-6- carboxaldehyde 12.3 g.) and l-ephedrine (16.5.g.) are dissolved in about 150 ml. of benzene. The benzene is removed under vacuum and the residue taken up in about 150ml. of isopropyl ether. The solution is filtered, then cooled to 13 C. to yield-crystals of 2- endo-bicyclo[3. 1 .0]hex-2-en-6-yl)-3,4-dimethyl-5- phenyl-oxazolidine, 11.1 g., m.p. 9092 C. Three recrystallizations from isopropyl ether, cooling each time to about -2 C, yield crystals of the oxazolidine, 2.2 g., m.p. 100-103 C., now substantially a single isomeric form as shown by NMR. g The above re-crystallized oxazolidine (1.0 g.) is dissolved in a few ml. of dichloromethane, charged to a g. silica gel column and eluted with dichloromethane. The silica gel is chromatography-grade, (Merck), 0.05-0.2-mm. particle size, with about 45 g. water per 100 g. Fractions of the eluate are collected, and those shown by thin layer chromatography (TLC) to contain acetic acid, is heated at reflux for about 5.5 hrs. using a Dean and Stark-trap to remove water. The benzene is then removed by evaporation leaving the formed oxazolidine as solids which are dissolved in methanol. On cooling the methanol solution, there is obtained one of the diastereomeric oxazolidines, 1.57 g., m.p. 161-166 C., [01],, 7.5 in chloroform, now substantially a single isomeric form as shown by NMR. NMR peaks at 0.63 (doublet), 0.72, 1.23, 2.38, 3.52, 3.95 (doublet) and 4.94 (doublet) 8.  
 Following the procedure of Example 13, the above I crystallized oxazolidine is converted on a silica gel column to an optically active isomer of the desired Formula-lV compound, 0.56 g., m.p.t. 43-47 C. [01],, +83 in chloroform; called the isomer of Example 14-A herein.  
  B. The mother liquor from A is concentrated and chilled to 13 C., to yield another diastereomeric oxazolidine, 1.25 g., m.p. 118130 C., [a],, +1 1.7 in chloroform; NMR peaks at 0.63 (doublet), 0.72, 1.23, 2.38, 3.52, 3.99 (doublet) and 5.00 (doublet) 8.  
 Following the procedure of Example 13, the crystal- I lized oxazolidine is converted on a silica gel column to an optically active isomer of the Formula-1V comthe enantiomorph of the oxazolidine of Example 14A,  
 the desired compound are combined and evaporated to an oil (360 mg.). This oil is shown by v NMR to be desired Formula-l compound, endo-bicyclo[3.1.0]hex-2- ene-6-carboxaldehyde, substantially free of the ephedrine, in substantially a single optically-active isomeric form; called the isomer of Example 13-A herein. Points on the circular d chroism curve are-(A in nm, 0): 350, 0; 322.5, 4,854; 312, 5,683; 302.5, 4,854; 269, 0; 250,- 2,368; 240, 0; and 210, 34,600.  
 B. The mother liquors of the oxazolidine are combined and evaporated to crystals, taken up in dichlorohyde.  
  Following the procedures of Example 13, the exo Formula-l bicyclo[ 3. 1 .O]hex-2-ene-6-carboxaldehyde is converted to the oxazolidine of dor l-ephedrine and resolved into its optically active isomers.  
 EXAMPLE 14 Resolution of Acetal Ketone (Formula IV: R, and R taken together are CH C(CH -CH andis endo).  
 A. A solution of 2.35 g. of the Formula-IV acetal ketone of Example 10 (wherein the acetal is prepared from 2,2-dimethy1-1,3-propanediol) and l-ephedrine (1.65 g.) in benzene (15 ml.), together with 1 drop of mp C., [01],, +7.5 in chloroform.  
  Following theprocedure of Example 13, the crystallized oxazolidine is converted on a silica gel column to an optically active isomer of the desired Formula-IV identical to that obtained in Example 14-B above.  
  Following the procedures of Example 14, the exo Formula-IV acetal ketone of Example 10 is converted to the oxazolidine of dor l-ephedrine and resolved into its optically active isomers.  
  Any one of the above resolved oxazolidines is hydrolyzed to the 0x0 compoundand ephedrine by contact with water, preferably with an acid catalyst, as is known .in the art (see Elderfeld, l-leterocyclic Compounds,  
 Vol.5, page 394, Wiley, N.Y., 1957). Thus, the oxazolidine of l-ephedrine and the Formula-1V acetal ketone (Example 14A, 5.0 g.) is stirred in a solution of tetrahydrofuran-water-acetic acid (25 ml.: 25 ml.: 5  
 . ml.) for 4 hrs. at about 25 C. under nitrogen. The solvents are removed under reduced pressure at 25-40 C., and the residue is mixed with 25 ml. of water. The mixture is extracted several times with benzene, and the combined benzene layers are washed with water, dried over sodium sulfate, and finally concentrated under reduced pressure to the optically active Formula-lV acetal ketone having the same properties as reported above following section A. An alternate method of hydrolyzing the oxazolidine is on a silica gelwater column according to Example 13, thereafter eluting the released oxo compound and recovering same by conventional means.  
 EXAMPLE 15 Resolution of Tricyclic Lactone Aldehyde (Formula VI: isendo).  
  A.&#39;A solution of the endo Formula-VI lactone aldehyde (0.5 g.) of Example 4 and l-ephedrine (0.5 g.) in  
 benzene (20 ml.) is concentrated under vacuum to a residue. The residue is treated with diethyl ether to yield crystals of an oxazolidine mixture. Recrystallization of the mixture from methanol yields an oxazolidine, m.p. 133.5-1345. Thereafter. hydrolysis of the oxazolidine on a silica gel column following the procedure of Example 13 yields an optically active isomer corresponding to the mirror image of the Formula-Vl lactone akdehyde, which is thereafter recovered by conventional means and is hereinafter identified as the isomer of Example l-A.  
  B. Following the procedure of Example l5-A. but replacing l-ephedrine with d-ephedrin&#39;e in preparing the oxazolidine, the optically active isomer corresponding to the Formula-VI lactone aldehyde is obtained. hereinafter identified as the isomer of Example l5-B.&#34;  
  Following the procedures of Example 15, the exo Formula-VI lactone aldehyde is resolved into its optically active isomers.  
 EXAMPLE l6 Optically Active Tricyclic Glycol (Formula VIII of Chart A: W is l-pentyl and is endo); PGE ,PGF- their ent-Compounds and their lS-Epimers.  
  Refer to Chart C. Following the procedures of Examples l to 6, inclusive, but using the Formula-l endobicyclo-[3.l.O]hex-2-ene-6-carboxaldehyde isomer of Example l3-A, there is obtained the Formula-VIII tricyclic glycol, wherein W is l-pentyl and is endo, as an optically active isomer. Following the procedures of Example this isomer is transformed to the optically active Formula-IX and Formula-X compounds wherein W is l-phenyl.  
  Likewise. using the Formula-l isomer of Example l3-C, there are obtained the enantiomorphic Formula- Vlll, -IX, and -X compounds. I  
  Each of-the Formula-X isomers is transformed to the corresponding PGE ent-PGE and their -epimers, using methods known in the art by the steps shown in Chart C. Thus, PGE is obtainedfrom the optically active Formula-X diol prepared from the Formula-l aldehyde isomer of Example l3-A, ent-PGE- is obtained from the enantiomorphic Formula-X diol prepared from the Formula-l aldehyde isomer of Example l3-C.  
  Furthermore, again using the optically active Formula-Vlll, -IX, and -X compounds&#39;prepared above, but following the steps of Chart E, using methods generally known in the art, there is obtained the corresponding PGF ent-PG F and their IS-epimers.  
  Following the procedures of Examples 1 to 6, inclusive, but substituting the optical isomers of the exo Formula-l aldehyde of Example 13 for the endo aldehyde, there are obtained the corresponding optically active exo Formula-VIII tricyclic glycols and Formula-IX bismesylates, which are converted to the isomeric Formula-X diols and thence to the corresponding PGE ent-PGE and their l5-epimers, PGF PGF and their IS-epimers.  
 EXAMPLE l7 P015 ent-PGE and their l5-Epimers,i(Formula xxu of Chart D: indicates the a or [3 configuration).  
  Refer to Chart D. Following the procedures of Example l3, the endo Formula-I bicyclohexene aldehyde is resolved into its two optically active isomeric forms. Following the procedures of Example I l and thereafter, each of the Formula-l isomers is transformed to the corresponding Formula-X diol in its a and ,3 configurations and thence to the corresponding PGE ent-PGE and their IS-epimers.  
  Following the procedures of Examples 14 and 15, the endo Formula-IV acetal ketone or the Formula-VI lactone aldehyde are resolved into their respective optically active isomeric forms. Following the procedures of Example 1 l and thereafter, each of the Formula-IV or Formula-VI isomers is transformed to the corresponding Formula-X diol in its a and B configurations and thence to the corresponding PGE ent-PGE and their l5-epimers.  
  Thus, PGE is obtained from the optically active Formula-X diol prepared from the Formula-IV Acetal ketone of Example l4-A or the Formula-VI lactone aldehyde of Example l5-B; ent PGE is obtained from the enantiomorphic Formula-X diol prepared from the Formula-IV acetal ketone of Example l4-C or the Formula-VI lactone aldehyde of Example lS-A.  
  Likewise, employing the exo forms of the Formula-l, -IV, and -V1 compounds, these are resolved into their respective optically active isomeric forms and transformed to the corresponding Formula-X diol and thence to the corresponding PGEg, ent-PGE and their l5-epimers.  
  Likewise, following the procedures of Example 11 and thereafter, the optically active Formula-VIII glycol in its isomeric forms, wherein W is l-pent-2-ynyl and &#39;7 indicates attachment of the moiety to the cyclopropane ring in exo or endo configuration is subjected successively to the following reactions:  
  a. replacement of the glycol hydrogens by an alkanesulfonyl group, R O S-, wherein R is alkyl of one to 5 carbon atoms, inclusive;  
  b. mixing with water at a temperature in the range of 0 to C. to form a bicyclic lactone diol;  
 c. separation of the diols of a and B configuration;  
 d. transformation to a bis(tetrahydropyranyl) ether;  
 e. reduction of the lactone oxo group to a hydroxy group; i  
  f. &#39;Wittig alkylation with a compound of the formula Hal-(CH COOH wherein Hal is bromo or chloro;  
 g. oxidation of the 9-hydroxy to oxo; and  
  h. transformation of the two tetrahydropyranyloxy groups to hydroxy groups; with the proviso that, before or after any of the steps a to h, the C E C- moiety is reduced to cis CH=CH-, thereby forming PGEg, ent-PGE or their IS-epimers.  
 . EXAMPLE l8 PGF ent-PGFg and their IS-epimers, (Formula XXVI of Chart F: indicates the a or B configuration).  
 Refer to Chart F. Following the procedures of Example 13, the endo Formula-I bicyclohexene aldehyde is resolved into its two optically active isomeric forms. Following the procedures of Example 12 and thereafter, each of the Formula-l isomers is transformed to the corresponding Formula-X diol in its a and B configurations and thence to the corresponding PGF ent- PGF and their IS-epimers.  
  Following the procedures of Examples 14 and 15, the endoFormula-IV acetal ketone or the Formula-VI lactone aldehyde are resolved into their respective optically active isomeric forms. Following the procedures of Example 12 and thereafter, each of the Formula-IV or Formula-VI isomers is transformed to the corre-