The stereoselective synthesis of α-substituted β-amino secondary alcohols based on the proline-mediated, asymmetric, three-component Mannich reaction and its application to the formal total synthesis of nikkomycins B and Bx

Yujiro Hayashi, Tatsuya Urushima, Makoto Shin, Mitsuru Shoji

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42 Citations (Scopus)

Abstract

A general method for the asymmetric synthesis of α-substituted β-amino secondary alcohols is described, which comprises the four-reaction sequence (1) the proline-mediated, asymmetric, three-component Mannich reaction of two different aldehydes, (2) nucleophilic carbon addition to aldehyde, (3) oxidation of the resulting alcohol to the corresponding ketone, and (4) diastereoselective reduction with LiAlH(O-t-Bu)3 or catecholborane. The former reductant afforded the 1,2-syn isomer, while the latter gave the 1,2-anti isomer stereoselectively. The present method was successfully applied to the efficient asymmetric synthesis of the N-terminal amino acid moiety of nikkomycin B and BX.

Original languageEnglish
Pages (from-to)11393-11404
Number of pages12
JournalTetrahedron
Volume61
Issue number48
DOIs
Publication statusPublished - 2005 Nov 28

Keywords

  • Asymmetric synthesis
  • Mannich reaction
  • Nikkomycin
  • Proline
  • Three-component reaction

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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