The mechanism investigation in substitution of 21-bromo-3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-one with nucleophiles

Chun Yen Chen, Fung Fuh Wong, Yueh Hsien Lee, Shan Yen Chou, Jiann Jyh Huang, Mou Yung Yeh

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3 Citations (Scopus)

Abstract

A mechanistic study on the nucleophilic substitution of a strictly geometric 21-bromo-3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-one was described. Reaction of the α-bromoketone with excess lithium imidazole followed by the addition of extra bases including n-butyllithium, methyllithium, lithium piperidine, and lithium pyrrolidine provided unexpected α-nucleophilic carbonyl adducts that derived from strong base. Data from HPLC and proton NMR suggested an epoxide as the intermediate. Two possible reaction pathways were proposed for the nucleophilic substitution reaction. One pathway is the normal SN2 substitution reaction, directly provided the imidazoly product without the formation of the unexpected α-substituted products. The other pathway went through an epoxide intermediate, in which imidazole anion or the strong bases added would attack from the less hindered site of the epoxide to give the substitution product. {A figure is presented}.

Original languageEnglish
Pages (from-to)942-948
Number of pages7
JournalSteroids
Volume71
Issue number11-12
DOIs
Publication statusPublished - 2006 Nov
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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