Development of Novel Methods for Preparing Chiral Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by Asymmetric Esterification
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- Nakata Kenya
- Department of Applied Chemistry, Faculty of Science, Tokyo University of Science
Bibliographic Information
- Other Title
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- 不斉エステル化反応によるキラルな非ステロイド性抗炎症剤(NSAIDs)の新規供給法の開発
- フセイ エステルカ ハンノウ ニ ヨル キラル ナ ヒステロイドセイ コウエンショウザイ(NSAIDs)ノ シンキ キョウキュウホウ ノ カイハツ
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Description
A novel and efficient method for preparing chiral 2-arylalkanoic acid derivatives, including non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, ketoprofen, fenoprofen, flurbiprofen, and naproxen, and their esters by asymmetric esterification is presented in this paper. A variety of optically active carboxylic esters are produced by the kinetic resolution of racemic 2-arylalkanoic acids with achiral alcohols, using carboxylic anhydrides in the presence of chiral acyl-transfer catalysts. It was found that the combination of the modified benzotetramisole-type catalyst, (S)-β-Np-BTM, and a newly designed nucleophile, di(α-naphthyl)methanol, in the presence of a carboxylic anhydride, p-methoxybenzoic anhydride (PMBA) or pivalic anhydride (Piv2O), is most suitable for producing the corresponding chiral esters from 2-arylpropionic acid derivatives, with high enantiomeric excess under very mild reaction conditions. Using this new chiral acylation system, fairly broad substrate scope could be realized despite the multi-functional groups on the aromatic ring of the substrate. It was also revealed that ortho-substituted aromatic compounds, especially, 2,5-disubstituted aromatic ones were the most suitable compounds for providing a high selectivity.<br>
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 132 (9), 993-1000, 2012-09-01
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390001206128540800
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- NII Article ID
- 130001888734
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- NII Book ID
- AN00284903
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- COI
- 1:STN:280:DC%2BC3s%2Fht1CitA%3D%3D
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- ISSN
- 13475231
- 00316903
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- NDL BIB ID
- 023961643
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- PubMed
- 23023415
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed