摘要 許多疾病被研究證時與 PTP 在人體的作用機制失衡有關，例如第二型糖尿病便是與 PTP-1B 有關的典型例子。 因而，我们利用固相組合式化學成功設計出一套可快速合成具四種不同變化取代的 5,6-Dihydro-pyran-2-one 及其衍生物，以期能找到成功模擬 PTP-1B 在生物體中所扮演的角色，並在我们設計的分子中加入不同的 Binding site，希望能提高其對 PTP-1B 的專一性，並對藥物發展作出貢獻。 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.
