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

Research output: Contribution to journalArticle

41 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
Externally publishedYes

Fingerprint

Amino Alcohols
Proline
Aldehydes
Isomers
Alcohols
Reducing Agents
Ketones
Carbon
Amino Acids
Oxidation
nikkomycin B

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

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. / Hayashi, Yujiro; Urushima, Tatsuya; Shin, Makoto; Shoji, Mitsuru.

In: Tetrahedron, Vol. 61, No. 48, 28.11.2005, p. 11393-11404.

Research output: Contribution to journalArticle

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AU - Hayashi, Yujiro

AU - Urushima, Tatsuya

AU - Shin, Makoto

AU - Shoji, Mitsuru

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N2 - 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.

AB - 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.

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KW - Proline

KW - Three-component reaction

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