Synthesis of 3β-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene and Reductive Nucleophilic Attack on a Branched Aliphatic Aldehyde

Toshiya Nagai, Kengo Hanaya, Shuhei Higashibayashi, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

Abstract

3β-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene, which has a double bond between C-9 and C-11 and a phenylsulfenyl group on the terminus of the side chain, is a potential synthetic intermediate for steroids with 9,11-unsaturation or 9,11-seco skeletons. We describe here the synthesis of the title compound from 17-ethylenedioxy-3-acetoxyandrosta-3,5-dien-11-one. The introduction of an ethylene unit to 3β-tert-butyldimethylsiloxyandrosta-5,9(11)-dien-17-one by the action of ethyltriphenylphosphonium bromide under basic conditions resulted in an inseparable mixture of two stereoisomeric products (5 : 1). However, in the subsequent step, only the (Z)-isomer was susceptible to the Lewis acid-catalyzed ene reaction with formaldehyde, giving a stereochemically pure product with the desired configuration. Within three steps, the ene-product was derivatized to the title compound, with a total yield of 53% over seven steps. Reductive terminal anion formation by treatment with lithium di-tert-butylbiphenyl (LiDBB) and subsequent nucleophilic attack on a branched aliphatic aldehyde was demonstrated, with an eye toward the introduction of side chains, especially for steroids with oxygen functionality at C-23.

Original languageEnglish
Pages (from-to)334-338
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume66
Issue number3
Publication statusPublished - 2018 Jan 1

Keywords

  • Ene reaction
  • Lithium di-tert-butylbiphenyl (LiDBB)
  • Phenyl sulfide
  • Pregna-5,9(11),17(20)-triene
  • Reductive nucleophilic attack

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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