SYNTHESIS OF BIOACTIVE MOLECULES VIA VINYL SULFONES

提出了一个五年计划，继续探索新的合成 战略采用乙烯基砜作为重点， 生物学上重要的天然产物和 非天然产物 这项建议有三个主要项目：（1）调查 作为α-磺酰基前体的α-杂原子取代的砜 阴离子和α-磺酰基。这些中间体将用于 在新的中环成环反应的发展中， 全手性细胞松弛素C103的全合成;（2）全手性细胞松弛素C103的全合成 抗白血病药物高三尖杉酯碱104合成 目前处于II期临床试验阶段。a的分子内转酰化 三尖杉碱衍生物将用于合成高度受阻的 （3）全合成了三个同手性的吡咯稠合的 前列环素类似物151-153，通过计算机建模预测为 血小板聚集的异常有效的抑制剂。这项研究应 为预防嗜中性粒细胞介导的 再灌注期间心肌的氧化损伤，以及提供 具有作为抗转移剂的潜力的新材料。

A five-year plan is proposed for the continued exploration of new synthetic strategies employing vinyl sulfones as the focal point of multiply-convergent total syntheses of biologically important natural and unnatural products. This proposal has three major project areas: (1) The investigation of alpha-heteroatom-substituted sulfones as progenitors for alpha-sulfonyl anions and alpha-sulfonyl radicals. These intermediates will be utilized in the development of new medium-ring annulation reactions as applied to the total synthesis of homochiral cytochalasin C 103; (2) The total synthesis of homochiral homoharringtonine 104, an antileukemia agent currently in Phase II clinical trials. Intramolecular transacylation of a cephalotaxine derivative will be exploited to synthesize a highly hindered ester; (3) The total synthesis of three homochiral, pyrrole-fused prostacyclin analogs 151-153, predicted by computer modeling to be exceptionally potent inhibitors of platelet aggregation. This study should provide important new agents for the prevention of neutrophil-mediated oxidative injury of the myocardia during reperfusion, as well as affording new materials which have potential as antimetastatic agents.