Application of the Lewis Acid-Lewis Base Bifunctional Asymmetric Catalysts to Pharmaceutical Syntheses : Stereoselective Chiral Building Block Syntheses of Human Immunodeficiency Virus (HIV) Protease Inhibitor and β_3-Adenergic Receptor Agonist
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概要
- 論文の詳細を見る
Chiral building block syntheses of promising drugs were achieved using two types of catalytic stereoselective cyanosilylatiuns of aldehydes promoted by Lewis acid-Lewis base bifunctional catalysts 1 and 2 as the key steps (diastereoselective cyanosilylation of amino aldehyde and enantioselective cyanosilylation). In the first part of this article, syntheses of chiral building blocks (6) of Atazanavir (3: human immunodeficiency virus (HIV) protease inhibitor) using the bifunctional catalyst 2 are discussed. The reaction of Boc-protected phenylalaninal 21 in the presence of 1 mol% catalyst 2 selectively afforded the anti isomer 22 as the major product (diastereomeric ratio=97:3), which was successively converted to the corresponding epoxide 6 in six steps. In the second part, we describe a chiral building block synthesis of β_3-adrenergic receptor agonists. The enantioselective cyanosilylation of 3-chlorobenzaldehyde (38) with 9mol% catalyst 1 gave the chiral cyanohydrin 39, which was converted to β-hydroxyethylamine 40 by reduction. Moreover, the chiral ligand of catalyst 1 could be recovered without column chromatography and reused without decreasing its activity.
- 公益社団法人日本薬学会の論文
- 2003-06-01
著者
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Kanai Motomu
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Kanai Motomu
Graduate School Of Pharmaceutical Science The University Of Tokyo
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Shibasaki Masakatsu
Graduate School Of Pharmaceutical Science The University Of Tokyo
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NOGAMI Hiroyuki
Chemicals Development Laboratories, Mitsubishi Rayon Co., Ltd.
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Nogami H
Chemicals Development Laboratories Mitsubishi Rayon Co. Ltd.
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