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In the present paper, the preparation of 3β-hydroxy-17β-dimethyl- tert-butylsilyloxy-5-azaandrostane (15) in fourteen steps is described. B-nor-17-oxoandrost-5-en-3β-yl acetate (1) 1,2 was used as the starting material, which was transformed to the key intermediate of the synthesis, B-nor-17β-dimethyl-tert-butylsilyloxyandrost-4-en-3β-yl acetate (7).

Beckmann rearrangement of (Z)-cholest-4-en-6-one oxime (4) (prepared in 4 steps starting from cholest-5-en-3β-ol ο1)) with thionyl chloride in dioxane solution afforded an enamide-type lactam, i.e. 7-aza-B-homocholest-4-en-6-one (6) as a single product. Photoreaction of the same compound in methanol or benzene-acetic acid solution gave a mixture of products, with the formation of the parent ketone 3 and the occurrence of Z/E isomerization, while the lactam 6 was obtained only when the reaction was performed in methanol and then in very low yield (7%)., Bekmanovo premeštanje (Z)-holest-4-en-6-on oksima (4) (koji je dobijen u 4 faze, polazeći od holest-5-en-3 β-ola (1)) sa tionil-hloridom u dioksanskom rastvoru, kao jedini proizvod daje laktam enamidnog tipa, tj. 7-aza-B-homoholest-4-en-6-on (6). Fotoreakcijom istog jedinjenja u metanolu ili u rastvoru benzen-sirćetna kiselina, nastaje smesa proizvoda koju čine polazni keton 3 i proizvodi Z/E izomerizacije, dok je laktam 6 dobiven u vrlo niskom prinosu (7%) samo u metanolnom rastvoru.

The acid-catalyzed reaction of (Z)- and (E)-B-nor-5,10-seco-ketones 2 and 3 resulted in an intramolecular cyclization to give the 5-hydroxy-A-nor-1β,5β-10(19)-methylidene derivative 8, the 5β-hydroxy-A-nor-1(10)-unsaturated compound 9 and the 5β,10β-dihydroxy A-nor-product 10, from the (Z)-isomer and the 5-hydroxy-A-nor-1β,5β-10(19)-methylidene product 11, from the (E)-isomer. Upon UV-irradiation, the (Z)- and (E)-seco-ketones 2 and 3 underwent a reversible (Z)/(E) and (E)/(Z)-isomerization and in addition to a transannular photocyclization to afford the 10(19)-methylidene derivatives 8 and 11, respectively, while photolysis of the 10(19)-methylidene-B-nor-5,10-seco-ketone 4 gave the oxetane derivative 12., Kiselo-katalizovana reakcija (Z)- i (E)-B-nor-5,10-seko-ketona 2 i 3 rezultuje u intramolekulskoj ciklizaciji dajući 5-hidroksi-A-nor-1β,5β-10(19)-metilidenski derivat 8, 5β-hidroksi A-nor-1(10)-nezasićeno jedinjenje 9 i 5β,10β-dihidroksi-A-nor-proizvod 10, iz Z-izomera, i 5-hidroksi-A-nor-1β,5β-10(19)-metilidenski proizvod 11, iz E-izomera. (Z)- i (E)-Seko- ketoni 2 i 3 UV-ozračivanjem podležu reverzibilnoj (Z)/(E) odnosno (E)/(Z) izomerizaciji, kao i transanularnoj fotociklizaciji dajući 10(19)-metilidenske derivate 8 odnosno 11, dok se fotolizom 10(19)-metilidenskog-5,10-seko-ketona 4 gradi oksetanski derivat 12.

Expoxidation of cholesta-5,8-dien-3β-yl acetate (1) with peracids takes place preferentially at the more highly substituted Δ8-olefinic double bond to give: (a) with monoperphthalic acid, 8α,9α-epoxycholest-5-en-3β-yl acetate (2) (in 39 % yield) and 9α-hydroxy-5α,6α-epoxycholest-8(14)-en-3β-yl acetate (3) (in 30 % yield); and (b) with m-chloroperbenzoic acid, the 8α,9α-epoxide 2 (64 %) and 5α,6α-epoxy derivative 3 (20 %). Some chemical transformations of the obtained epoxides are described., Epoksidacija holesta-5,8-dien-3β-il acetata (1) sa perkiselinama prvenstveno se odvija na više supstituisanoj Δ8-olefinskoj dvoguboj vezi pri čemu se dobija: (a) sa monoperftalnom kiselinom, 8α,9α-epoksiholest-5-en-3β-il acetat (2) (u prenosu od 39 %) i 9α-hidroksi-5α,6α-epoksiholest-8(14)-en-3β-il acetat (3) (u prenosu od 30 %); i (b) sa m-hlorperbenzoevom kiselinom, 8α,9α-epoksid 2 (u prenosu od 64 %) i 5α,6α-epoksi derivat 3 (u prenosu od 20 %). Opisane su i neke hemijske transformacije dobijenih epoksida.

A simple one-put procedure for the synthesis of the 5,6-seco-steroidal acids 9a,b in described in this paper. It consists of the epoxidation of the ▲ 5 -steroids, i.e., cholesteryl acetate (8a) and 17-oxo-aandrost-5-en-3β-yl acetate (8b) with peracetic acid (generated in situ by the H 2 WO 4 H 2 O 2 system), followed by the CrO 3 /H 2 SO_ oxidation of the thus formed epoxides. The 5,6-seco-steroidal acids 9a,b (obtained in about 90% and 77% yield, respectively) are transformed to the corresponding B-norsteroids by the known method (Beayer-Villiger oxidation and subsequent thermolysis of the respective β-lactones).

5-Hydroxy-5α-cholest-8-en-3β-yl acetate (8) (prepared in 6 steps starting from 7-dehydrocholesteryl acetate (1) was transformed with ruthenium tetroxide to 5-hydroxy-8,9-dioxo-8,9-seco-5α-cholestan-3β-yl acetate (9). Treatment of the latter 8,9-seco-5-hydroxy derivative with lead tetraacetate (LTA) or mercuric oxide/iodine reagent (HgO/I2) resulted, instead of the expected oxidative β-fragmentation of its C(5)-C(10) bond, in the competing non-regio and non-stereoselective acetoxylation of the α-positions next to the 8- and 9-oxo functions (with LTA), and in the ≈ 82% recovery of the starting material (with HgO/I2). The results are discussed in terms of the strong hydrogen bonding which exists between the 5α-hydroxyl and the 8-oxo group.

In this paper is described a synthetic pathway to the modified 5, 10:8, 14-bisfragmentation cholestene derivatives 10, 11 and 12, which involves introduction of the Δ8(14)-double bond and 5α-hydroxyl group in the cholestane molecule and subsequent cleavage of the olefinic C(8)-C(14) bond (with ruthenium tetroxide) and C(5)-C(10) bond (with mercuric oxide/iodine or lead tetracetate/iodine).