Synthesis of a novel Small Molecular Weight Peptidomimetic non-competitive Inhibitors of Protein Tyrosine Phosphatase 1B

• Main Authors: Chung-Wel Tsai, 蔡宗衛
• Other Authors: Wen-Ren Li
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/67424465239606829495

碩士 === 國立中央大學 === 化學研究所 === 92 === ABSTRACT There is evidence that type II diabetes has a connection with insulin resistance. Protein tyrosine phosphatase 1B(PTP 1B) attenuates insulin signal transduction by catalyzing the dephosphorylation of the insulin receptors(IR) and is thus a vital target of potenyial drugs for treatment of type II diabetes. A peptidomimetic sequence targeting at the binding site on PTP1B combined with a suicide inhibition function is the central concept of our design of potential PTP1B inhibitors. A mini library of 5,6-Dihydro-pyran-2-ones was synthesized by a highly efficient scheme which is applicable both in solution-phase synthesis and solid-phase combinatorial synthesis. C-C single bond formation by a stereoselective carbonyl addition gives well-defined stereochemistry in our skeleton and ring closing metathasis(RCM) was applied to afford the dihydropyranone lactone.