Synthesis of a New Dual Metalloprotease Inhibitor. I. Diastereoselective Alkylation of Protected 6-Oxopipecolic Acid Esters
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概要
- 論文の詳細を見る
Diastereoselective methylation of the enolate generated from various protected 6-oxopipecolic acid esters (3aa-3cd) was studied. The protecting groups on the carboxylic acid and amino groups significantly influenced the trans/cis selectivity in the methylation reaction. The optimal substrate (3ca), bearing benzhydryl ester and carbobenzyloxy moieties gave a trans/cis isomer ratio of ca. 4 : 1. Investigation of the reaction conditions revealed that the reaction solvent, alkylating reagent, and base employed to generate the enolate, were decisive factors for diastereoselectivity. Further optimization of reaction conditions, including the amounts of the reagents and their addition sequence enabled maximization of reaction conversion and minimization of by-products to produce the trans rich 5-methyl-6-oxopipecolic acid ester (4ca) on a large scale.
- 公益社団法人日本薬学会の論文
- 1999-11-15
著者
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Negi S
Eisai Co. Ltd. Kashima Plant Process Chemistry Research Laboratories
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Akamatsu Hiroshi
Eisai Co. Ltd. Tsukuba Research Laboratories
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Shimizu Toshihiro
Pharmaceutical Development Laboratories Pharmaceutical Production Division Takeda Chemical Industrie
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Komatsu Y
National Institute Of Advanced Industrial Science And Technology
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Negi Shigeto
Eisai Co. Ltd. Kashima Plant Process Chemistry Research Laboratories
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Komatsu Yuki
Eisai Tsukuba Research Laboratories
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AKASAKA Kozo
Eisai Co., Ltd., Tsukuba Research Laboratories
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TAGAMI Katsuya
Eisai Co., Ltd., Tsukuba Research Laboratories
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SHIMIZU Toshikazu
Eisai Co., Ltd., Tsukuba Research Laboratories
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SHIMOMURA Naoyuki
Eisai Co., Ltd., Tsukuba Research Laboratories
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KIMOTO Yuichi
Eisai Co., Ltd., Kashima Plant, Process Chemistry Research Laboratories
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Akasaka Kozo
Eisai Co. Ltd. Tsukuba Research Laboratories
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Kimoto Y
Eisai Co. Ltd. Kashima Plant Process Chemistry Research Laboratories
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Tagami Katsuya
Eisai Co. Ltd. Tsukuba Research Laboratories
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Shimomura N
Kobe Univ. Kobe
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