On the acid-catalyzed D-homoannulation of pregnanetriol 20-sulfate and its C-20 isomeric sulfate

Article abstract of DOI:10.1248/cpb.42.1736

To demonstrate the rearrangement reactions of pregnanetriol 20-sulfates in hot acid hydrolysis, 5β-pregnane-3α,17α,20α-triol 20-sulfate (8a) and its C-20 isomer 5β-pregnane-3α,17α,20β-triol 20-sulfate (12a) were heated in 3M hydrochloric acid. As the sole D-homosteroidal product of each sulfate, 3α-hydroxy-17aβ-methyl-D-homo-5β-androstan-17-one (13a) and 3α-hydroxy-17α-methyl-D-homo-5β-androstan-17a-one (17a) were obtained from 8a and 12a, respectively, accompanied with several kinds of degradation products considered to be monohydroxysteroidal dienes. It became clear that the reaction of 8a proceeds via two steps: ring enlargement of 8a occurred at once to give 3α-hydroxy-17aα-methyl-D-homo-5β-androstan-17-one (14) as the intermediate, followed by isomerization to 13a as the final product. The mechanism of D-homoannulation was elucidated by hydrolysis of [20-¹³C]pregnanetriol 20-sulfate (8b, 12b). The D-homosteroid obtained from 8b contained a quantitative amount of the isotope only at C-17a, indicating that the ring-enlargement reaction of the 20α-sulfate proceeds with stereospecific migration of the C₁₃-C₁₇ bond. Compound 12b gave the ¹³C-labelled D-homosteroid enriched solely at C-17, which means that the D-homoannulation of 20β-sulfate occurs by stereospecific migration of the C₁₆-C₁₇ bond. The diene products from 8a and 12a were formed from the reaction intermediates 17α,20β-oxido-5β-pregnan-3α-ol (19) and 17α,20α-oxido-5β-pregnan-3α-ol (20), respectively. The mechanism of these rearrangement reactions is discussed.

Full text of DOI:10.1248/cpb.42.1736

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