Steroidal N-nitro-amines. Part 2. Denitroamination of steroidal 12β-, 17β-, 20β-, and 23R-nitro-amines

Abstract

20β-Nitroaminopregn-5-en-3β-yl acetate (13a), 17β-nitroamino-5α-androstan-3β-yl acetate (14), and 12β-nitroamino-(25R)-5α-spirostan-3β-yl acetate (15a) have been prepared by nitrosation of the corresponding oximes, followed by reduction with sodium borohydride. The 23-nitro-imine (12), obtained by reaction of sarsasapogenin acetate (10) with nitrous acid and boron trifluoride–diethyl ether complex, was similarly reduced to give 23R-nitroamino-(20S,22S,25S)-5β-spirostan-3β-yl acetate (16). Denitroamination of (13a) was achieved by treatment with acetic anhydride and pyridine to give the acetates of pregna-5,20-dien-3β-ol (17), pregn-5-ene-3β,20β-diol (18), 17α-methyl-D-homo-androst-5-ene-3,17aβ-diol (19), and 17α-methyl-12a-methylene-c(12a)-homo-18-norandrost-5-en-3β-ol (20). Under the same conditions the nitro-amine (14) afforded the acetates of 5α-androst-16-en-3β-ol (27a), 17β-methyl-18-nor-5α-androst-12-en-3β-ol (28a), 17-methyl-18-nor-5α-androst-13(17)-en-3β-ol (29a), and 17β-methyl-18-nor-5α-androst-13-en-3β-ol (30a). Denitroamination of (15a) took place through the expected c-nor-D-homo rearrangement producing 14 (13 → 12αH)abeo-(25R)-5α-spirost-13(18)-en-3β-yl acetate (31) in high yield and a minor amount of 14(13 → 12)abeo-(25R)-5α-spirost-12-en-3β-yl acetate (32). The trans-stereochemistry of the β-hydrogen-elimination produced in the denitroamination of (16) was established by using labelled sarsasapogenin (10) biosynthesized by Agave attenuata from [2-¹⁴C,(4R)-4-³H] mevalonic acid.