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1,25-Dihydroxycholecalciferol (23) was synthesized from A-ring precursor 18 and Windaus-Grundmann ketone 19 via cyclovitamin D 21. Key reactions include highly stereoselective (5 to 6) and stereospecific (13 to 14) cyclopropanations.

The 25-hydroxy and 1α,25-dihydroxy vitamin D3 metabolites are obtained by solvolytic rearrangements of the 1-desoxy and 1α-hydroxy cyclopropyl vinylogous alcohols 31 and 29, respectively, with simultaneous formation of the vitamin D structural triene and the 3-hydroxy function. Two complementary methods have been employed to direct the stereoselectivity of the samarium induced olefin cyclopropanations which ultimately lead to key chiral ring A precursors. One protocol uses the two stereogenic centers of the (R,R)-2,3-butanediol ketal moiety of 8, while the other method uses the allylic hydroxyl group of (R)-16.

Les substitutions nucleophiles des chromannes du titre avec le [cyano trimethyl] silane sont etudiees. Le catalyseur, TiCl 4 ou SnCl 4 , a une influence sur la regioselectivite des reactions

Several allylic isothiuronium salts 6 have been shown to yield 4-substituted 2-amino-5,6-dihydro-4H-1,3-thiazines (2; R3 = H) and the 2-phenylimino compound 10 on exposure to trifluoroacetic acid or trifluoroacetic acid-stannic chloride. The overall process constitutes a convenient transformation of readily available ketones or aldehydes 3 into the target hetero-cycles. The scope and limitations of this approach are discussed in terms of carbenium ion intermediates (7). Whereas this method successfully led to the imidazo[2,l-b][1,3]thiazine 13 (93% from 12), its application to the synthesis of 2-amino-2-thiazolines (eg. 14 15) or imidazo-[2,1-b]thiazoles (eg. 16 17) was unsuccessful. The 2-acetylimino derivatives 9 were found to be useful for purification of the 2-aminothiazines.

It has been established by an evaluation of 6 production samples ofall-rac-α-tocopheryl acetate that all 4 racemates (RRS/SSR, RRR/SSS, RSR/SRS and RSS/SRR) are consistently present in equimolar amounts (SD

As an extension of previous studies on the total synthesis of (2R,4′R,8′R)-α-tocopherol (1) [1] [2], (S)-(−)-2-(6-benzyloxy-2,5,7,8-tetramethylchroman)acetic acid (6), a pivotal intermediate, possessing the absolute configuration required for construction of 1 was prepared by optical resolution of the racemic modification 11. the latter substance was obtained by two routes, one emanating from the hydroxy acetal 7 [1] and the other based upon the Lewis acid mediated cycloaddition of trimethylhydroquinone to rac.-3-hydroxy-3-methylpent-4-en-l-yl acetate (16) giving rac. ethyl 2-(6-hydroxy-2,5,7,8-tetramethyl-chroman)acetate (12).

All eight stereoisomers of α-tocopheryl acetate have been synthesized in a state of high chemical and stereoisomeric purity. Key chiral side-chain intermediates were prepared from (+)-(S)-3-hydroxy-2-methylpropanoic acid. New routes to (2R, 4′ RS, 8′ RS)-α-tocopheryl acetate, a mixture of four diastereoisomers, were also developed. A sensitive gas chromatographic method was developed to determine the diastereoisomeric and enantiomeric purity of α-tocopherol samples as the methyl ethers. It was established for the first time that naturally occurring α-tocopherol is essentially a single enantiomer (2 R, 4′ R, 8′ R), synthetic all-rac-α-tocopherol an equimolar mixture of four racemates, and that natural (E)-(7 R, 11 R)-phytol is diastereoisomerically and enantiomerically homogeneous.

All eight stereoisomers of α-tocopheryl acetate have been synthesized in a state of high chemical and stereoisomeric purity. Key chiral side-chain intermediates were prepared from (+)-(S)-3-hydroxy-2-methylpropanoic acid. New routes to (2R, 4′ RS, 8′ RS)-α-tocopheryl acetate, a mixture of four diastereoisomers, were also developed. A sensitive gas chromatographic method was developed to determine the diastereoisomeric and enantiomeric purity of α-tocopherol samples as the methyl ethers. It was established for the first time that naturally occurring α-tocopherol is essentially a single enantiomer (2 R, 4′ R, 8′ R), synthetic all-rac-α-tocopherol an equimolar mixture of four racemates, and that natural (E)-(7 R, 11 R)-phytol is diastereoisomerically and enantiomerically homogeneous.

Asymmetric induction in 19-norsteroid total synthesis is discussed. It should be noted that the (S)-(+)-enedione can be made available by cyclization of the triketone with (S)-proline and its derivatives (asymmetric synthesis). Also mention must be made of the elegant approaches to progesterone and 11-substituted progesterones using biomimetic polyolefin cyclizations in which substantial asymmetric induction at several chiral centers is observed (diastereoselective synthesis). It is concluded that the successful utilization of asymmetric transformations demonstrated in the steroid field defines the potential of such processes and bodes well for their equally successful application in other areas of natural product synthesis.

(+/-)-2-Amino-7-oxa-3-thia-1-azaspiro[5,5]undec-1-ene (1a) and many of its derivatives exhibit significant activity in the phenylquinone writhing and yeast inflamed foot assays. In order to develop structure-activity relationships, the related spiroheterocycles, (+/-)-2-amino-7-oxa-3-thia-1-azaspiro[5,4]dec-1-ene (2), (+/-)-2-amino-3-thia-1-azaspiro[5,5]undec-1-ene (3), and (+/-)-2-amino-7-oxa-1-azaspiro[5,5]undec-1-ene (4), were examined. Of these, only 4 failed to show activity indicating that the analgetic properties displayed by compounds 1--3 are associated, mainly, with the 2-amino-1,3-thiazine ring system. In the 2-acylimino series, evidence is presented suggesting a contribution to the observed activity on the part of the spiroannulated ether ring as well. Both 1a and its p-fluorobenzoyl derivative 33 exhibit analgesic activity in the rat tail-flick assay.

In recent years, applications of asymmetric, amino acid mediated aldol cyclizations1,2 have led to major advances in steroid total synthesis.3 Typical of such processes is the conversion of prochiral triketone la 4 to the steroid CD-synthon, (S)-(+)-enedione 2a in high chemical and optical yield, under the influence of (S)- proline.1,2 This approach to the introduction of chirality is the foundation upon which several enantiospecific and highly efficient syntheses of biologically important steroids (19-norsteroids, A-ring aromatic steroids, androstanes) or their precursors are based.3

The (S)-(−)-chroman-2-acetic acid 5 and its derivatives are plvotal intermediates in various total syntheses of natural (2R,4′FJ,E′FJ)- a- tocopherol (1) developed in our laboratories. 1–5 Certain of these convergent schemes,1–3 involving coupling of C15-chroman and C14-side chain units possessing very high enantiomeric and diastereomeric purities, have also proven useful for construction of all 7 stereoisomers of natural a-tocopherol.6