Ring-c aromatic steroids. 17β-Methyl-18-norpregna-8,11,13-trienes

Abstract

Boron trifluoride-diethyl ether converts 20a.21 -diacetoxy-9a.l1 a-epoxy-17a-hydroxypregn-4-en-3-0ne (1 8) into 20a. 21 -diacetoxy-l7~-methyl-l8-norpregna-4,8,11,13-tetraen-3-one (1 9). An analogous c-aromatic steroid is similarly obtained from 9a.11 a-epoxy-l7a-methyltestosterone (9). From (1 9), by modifications of ring A and the 17a-side-chain, a series of 17p-methyl c-aromatic steroids has been prepared. The 5p configuration of the 3-ketone (21 ), obtained stereospecifically by hydrogenation of the A4-3-ketone (1 9) is deduced from 13C and l H n.m.r. data. Some acid-catalysed transformations of 1 7a-methyl-As(11)-testosterone (1 ) are reported.GENERAL routes to ring-c aromatic steroids have been explored by us in a programme to study the pharmacological properties of such substances. The impetus for such work comes in part from the isolation from fungi of viridin, a c-aromatic steroid,l and its related meta-bolites2 This paper records work based on Wagner-Meerwein migration of methyl from C-13 to C-17 upon elimination of a 17a-hydroxy. Before we commenced work, several other methods had been in use, viz. C-13+ C-12 methyl m i g r a t i ~n , ~ total ~ynthesis,~ and transformation from c-aromatic diterpenes.5In recent years Turner and his co-workers,6 and Hewett et have described work involving elimination-migration of 17-alcohols of the 17-methylandrostane group. We chose to work on pregnanes and corticoids to produce c-aromatic steroids of the 17p-pregnane series with oxygen functions on a 17a side-chain. The product. Where an 1 l-oxo-, 11 p-hydroxy-, or 11 pacetoxy-function is present, thermodynamic factors tend to favour instead the A12(13)-product (Scheme 1). Our work (below) suggests that even in the presence of A9(11)-unsaturation, proton loss from the rearranged C-13 carbonium ion occurs initially from C-14. SCHEME 1 17a-Methyl-A9(11)-testosterone (1) chosen as a model gave rise, on acid treatment, to a variety of products, With acetic acid-l0M-hydrochloric acid (1 : l), the re-OAcTABLE 1 'H Chemical shifts (CDC1, solutions; p.p.m. from SiMe,; J and Wit in Hz) Compounds H-4

Ionic Liquid-Promoted Wagner–Meerwein Rearrangement of 16α,17α-Epoxyandrostanes and 16α,17α-Epoxyestranes

“…Accordingly, several methods have been developed for the formation of ring C aromatic steroids, a number of them involving a Wagner–Meerwein rearrangement step. C aromatic steroids were obtained starting form 17α-alkyl-17β-hydroxy 9α,11α-epoxides via Lewis acid-induced methyl migration, epoxide ring opening, and dehydration . Another possibility was the Wagner–Meerwein rearrangement of 17α-hydroxy- or 17β-substituted-16α,17α-epoxy steroids followed by oxidation/aromatization.…”