Part I: Liquid-Phase Combinatorial Synthesis of 1,4-Benzodiazepine-2,5-diones as Endothelin Receptor Antagonists Part II: Synthesis of Biosynthetic Intermediate Analogues of Spinosyn A: An Approach to Investigation of Polyketide Combinatorial Biosynthesis

Abstract

第一部份：液相組合式合成1,4-Benzodiazepine-2,5-diones作為內皮素受體拮抗劑 我們利用2-nitrobenzoyl chloride作為anthranilic acid之合成對等物，於溶液相中合成出一系列1,4-benzodiazepine-2,5-dione衍生物。這些衍生物的N1、N4，與C3位置具有適當的取代基可以模擬endothelin-1之13-酪胺酸、14-苯丙胺酸、18-天門冬胺酸等胺基酸的支鏈。 基於成功的溶液相合成方法，我們亦發展了液相組合式合成法來建立1,4-benzodiazepine-2,5-diones分子庫。此一分子庫是以 Part I: Liquid-Phase Combinatorial Synthesis of 1,4-Benzodiazepine-2,5-diones as Endothelin Receptor Antagonists A series of 1,4-benzodiazepine-2,5-diones are prepared by using 2-nitrobenzoyl chloride as a synthetic equivalent of anthranilic acid in solution-phase. The derivatives have appropriate substituents at N1-, N4- and C3-positions to mimic the amino acid residues of Try-13, Phe-14, and Asp-18 in endothelin-1. Upon the successful solution-phase synthesis of 1,4-benzodiazepine-2,5-diones, we also explore a liquid-phase combinatorial synthesis to construct a library of 1,4-benzodiazepine-2,5-diones. The library is established by using the starting materials of