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

doi:10.1016/j.tet.2005.09.013

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 B_x

Yujiro Hayashi, Tatsuya Urushima, Makoto Shin, Mitsuru Shoji

Research output: Contribution to journal › Article › peer-review

43 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 B_X.

Original language	English
Pages (from-to)	11393-11404
Number of pages	12
Journal	Tetrahedron
Volume	61
Issue number	48
DOIs	https://doi.org/10.1016/j.tet.2005.09.013
Publication status	Published - 2005 Nov 28
Externally published	Yes

Keywords

Asymmetric synthesis
Mannich reaction
Nikkomycin
Proline
Three-component reaction

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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Hayashi, Y., Urushima, T., Shin, M., & Shoji, M. (2005). 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 B_x Tetrahedron, 61(48), 11393-11404. https://doi.org/10.1016/j.tet.2005.09.013

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 B_x . / Hayashi, Yujiro; Urushima, Tatsuya; Shin, Makoto et al.
In: Tetrahedron, Vol. 61, No. 48, 28.11.2005, p. 11393-11404.

Research output: Contribution to journal › Article › peer-review

Hayashi, Y, Urushima, T, Shin, M & Shoji, M 2005, '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 B_x ', Tetrahedron, vol. 61, no. 48, pp. 11393-11404. https://doi.org/10.1016/j.tet.2005.09.013

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title = "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 ",

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.",

keywords = "Asymmetric synthesis, Mannich reaction, Nikkomycin, Proline, Three-component reaction",

author = "Yujiro Hayashi and Tatsuya Urushima and Makoto Shin and Mitsuru Shoji",

note = "Funding Information: The authors are indebted to Professors Tohru Fukuyama and Hidetoshi Tokuyama of The University of Tokyo for their invaluable suggestions concerning the oxidation of furan and the usage of the ozone generator. This work was partially supported by Grand-in-Aid for Scientific Research on Priority Areas 16073219 from The Ministry of Education, Culture, Sports, Science and Technology (MEXT).",

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AU - Shin, Makoto

AU - Shoji, Mitsuru

N1 - Funding Information: The authors are indebted to Professors Tohru Fukuyama and Hidetoshi Tokuyama of The University of Tokyo for their invaluable suggestions concerning the oxidation of furan and the usage of the ozone generator. This work was partially supported by Grand-in-Aid for Scientific Research on Priority Areas 16073219 from The Ministry of Education, Culture, Sports, Science and Technology (MEXT).

PY - 2005/11/28

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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.

KW - Asymmetric synthesis

KW - Mannich reaction

KW - Nikkomycin

KW - Proline

KW - Three-component reaction

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