Reactions of steroidal epoxides with strong organic bases and an investigation into the syntheses of some labelled pregnane derivatives

摘要

Reactions of 5,6- and 4,5-epoxycholestane derivatives with strongbases were investigated.Epoxidation of 3a-acetoxycholest-5-ene also gave a new compound alongwith the anticipated epoxides. Interconversions of the latter were observed.Some possible mechanisms of its formation and rearrangements have beenpIioposed.No reaction was observed with any of the 5,6- and 4,5-steroidalepoxides employed in the present study, using potassium tertiary butoxideunder refluxing conditions. n-Butyllithium reacted only with5,6-epoxycholestanes bearing a ketal moiety at the C3 carbon. Opening ofthe ketal group was observed with n-butyllithium in the case of a ~-epoxide.The reaction was also investigated in the absence of epoxide functionality.A possible mechanism for the opening of ketal group has been proposed.Lithium diethylamide (LDEA) was found effective in rearranging5,6- and 4,5-epoxides to their ~orresponding allylic alcohols. Theserearrangements presumably proceed via syn-eliminations, however thepossibility of a corresponding anti-elimination has not been eliminated.A substituent effect of various functional groups (R = H, OH, OCH2CH20)at C3 has-been observed on product distribution in the LDEApromotedrearrangements of the corresponding epoxides.No reaction of these epoxides was observed with lithium diisopropylamide(LDA) •In the second part of the project, several attempts were made towardsthe sYRthesis of deoxycorticoste~one~17,2l,2l~d3' a compound desirable forthe 2l-dehydroxylation studies of deoxycorticosterone. Several routes wereinvestigated, and some deuterium labelled pregnane derivatives wereprepared in this regard. Microbial 21-hydroxylation of progesteronel7,21,21,2l-d4 by ~ niger led to loss of deuterium from C21 of the product.An effort was made to hydroxylate progesterone microbially under neutralcondtions.