A selenosulfonation-based approach to (22S,23E)-6β-methoxy-3α,5-cyclo-5α-ergost-23-en-22-ol, a key intermediate for brassinolide synthesis

Abstract

(22S,23E)-6β-Methoxy-3α,5-cyclo-5α-ergost-23-en-22-ol (2), an intermediate in the synthesis of brassinolide (μ) and related compounds, was synthesized by a new approach. (20S)-6β-Methoxy-3α,5-cyclo-5α-pregnane-20-carboxaldehyde (5) was converted to the corresponding 22S and 22R-24-yn-22-ol derivatives 6a and 6b by treatment with 3-lithio-1 -trimethylsilylpropyne, followed by tetra-n-butylammonium fluoride. The products were subjected to selenosulfonation, base-catalyzed isomerization, and selenoxide elimination to afford the respective 22S and 22R allenic sulfones 9a and 9b. The 22S isomer 9a underwent addition with lithium diisopropylcuprate – dimethyl sulfide complex, followed by reductive desulfonylation with magnesium in methanol, to afford 2, as well as smaller amounts of its 24(28) isomer 11a and (22E)-6β-methoxy-3α,5-cyclo-5α-ergosta-22,24(28)-diene (12). Similar treatment of 9b afforded 13, the 22R isomer of 2, as the principal product, as well as its 24(28) isomer 11b, and diene 12. Keywords: brassinolide, (22S,23E)-6β-methoxy-3α,5-cyclo-5α-ergost-23-en-22-ol, selenosulfonation, allenic sulfones.