Preparation of the Steroidal 1, 4, 11-Trien-3-ones and a Surprisingly Rapid Dienone-phenol Rearrangement

• Published in: Chemical & pharmaceutical bulletin Vol. 23; no. 11; pp. 2711 - 2727
• Main Authors: TAKEDA, KENICHI, TANIDA, HIROSHI, HORIKI, KUSUO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1975; Japan Science and Technology Agency
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.23.2711

25D-Spirosta-1, 4, 11-trien-3-one (5a) and androsta-1, 4, 11-trien-17β-ol-3-one acetate (16b) were prepared from hecogenin and 5β-androstane-3α, 12α, 17β-triol, respectively. The dienone-phenol rearrangements of these compounds were carried out and the structures of all reaction products were clarified. Rates of the rearrangement of 16b were determined in a 95 : 5 (w/w) mixture of acetic acid and acetic anhydride containing p-toluenesulfonic acid at 20° and varying acidity function H0. Comparison with a reference compound, androsta-1, 4-dien-17β-ol-3-one acetate (36), indicated for 16b a reactivity enhanced by a factor of 180 at 20°and H0=0. Products were found to be four kinds of the A-aromatic B-seco allyl acetates (at 20°and H0=-0.80 ; Δ9(11)-12α-OAc (25c) 75%, Δ9(11)-12β-OAc (25d) 2%, and Δ11(12)-9 (α and β)-OAc (26c) 23%) with the A-aromatic B/C cis Δ11(12)-steroid (27c) (3%). The results suggest important participation of the C-11 (12) double bond in the rearrangement of 16b. Treatment of the B-seco Δ9(11)-12α-allyl alcohol (25b) with the acid of H0=-1.86 at 80° led to the B/C cis steroid (27c) with a concurrent isomerization to an intermediate, B-seco Δ9(11)-12β-allyl acetate (25d), which is interpreted as a result of electrophilic aromatic substitution of an allyl cation formed from the B-seco Δ9(11)-12α-allyl alcohol.