A facile enantioselective synthesis of (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaninol via proline-catalyzed asymmetric α-aminooxylation and α-amination of aldehyde

被引：22

作者：

Rawat, Varun ^{[1
]}

Chouthaiwale, Pandurang V. ^{[1
]}

Chavan, Vilas B. ^{[1
]}

Suryavanshi, Gurunath ^{[1
]}

Sudalai, Arumugam ^{[1
]}

机构：

[1] Natl Chem Lab, Chem Engn & Proc Dev Div, Pune 411008, Maharashtra, India

来源：

TETRAHEDRON LETTERS | 2010年 / 51卷 / 50期

关键词：

Alzheimer's disease; alpha-Amination; Amino alcohol; alpha-Aminooxylation; Proline; GAMMA-SECRETASE INHIBITOR; ALZHEIMERS-DISEASE; ORGANOCATALYSIS; AMINOXYLATION; HYPOTHESIS; 1,2-DIOLS; ALCOHOLS; KETONES; ROUTE;

D O I：

10.1016/j.tetlet.2010.10.029

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A high-yielding enantioselective synthesis of the bioactive (S)-N-(5-chlorothiophene-2-sulfonyl)beta,beta-diethylalaninol (1), a Notch-1-sparing gamma-secretase inhibitor metabolite (with EC50 = 28 nM) effective in reduction of All production in vivo, has been realized starting from readily available 3-pentanone. The key steps of the synthesis are proline-catalyzed alpha-aminooxylation and alpha-amination of aldehyde: the latter contributing an overall yield of 45.2% and 98% ee. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6565 / 6567

页数：3

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