Design of the Nonenzymatic Effective Dehydration Condensation Reaction and its Application to the Synthesis of Biologically Active Molecules

2014 Fiscal Year Final Research Report

• Project/Area Number: 22350044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: SHIINA Isamu 東京理科大学, 理学部, 教授 (40246690)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 有機化学 / 有機合成化学 / 脱水縮合 / 不斉合成 / 不斉エステル化 / 速度論的光学分割 / 光学活性アルコール / 光学活性カルボン酸

Outline of Final Research Achievements

Various optically active carboxylic esters were produced by the kinetic resolution of racemic secondary benzylic alcohols using free carboxylic acids with pivalic anhydride and chiral acyl-transfer catalysts. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase. Furthermore, an efficient protocol was developed to produce chiral 2-arylalkanoic esters in high yields (up to 99%) from racemic carboxylic acids utilizing the racemization of the mixed anhydrides generated from acid components with pivalic anhydride in the presence of the acyl-transfer catalyst. This method was also successfully applied for the preparation of pharmacodynamically active (S)-enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen.

Free Research Field

有機合成化学