TUMOR INHIBITORS AND RELATED SUBSTANCES

该建议的重点是全合成 苦木类 具体目标包括quasimarin，bruceantin， 蓝胭脂酮 此外，我们还计划制备多种C（15）酯类化合物 为了检查结构要求， 生物活性。 假设膜胆固醇会在 构成了肿瘤发生的早期阶段，使我们专注于 开发一种有效的途径，以compactin，这已被证明是一个 3-羟基-3-甲基戊二酰辅酶A的有效竞争性抑制剂 还原酶，胆固醇生物合成中的速率控制酶。 作为 扩展早期的研究采用双环[2.2.1]庚烷化学，我们 计划立体定向地制备光学活性形式的硫霉素 和三种C（10）类似物[10 β-氟，10 β-甲基，和 10 β-甲氧硫霉素。

This proposal focuses on the total synthesis of antineoplastic quassinoids. Specific targets include quasimarin, bruceantin, and glaucarubinone. In addition, we plan to prepare a variety of C(15) esters related to A-norquasimarin in order to examine the structural requirements for biological activity. The hypothesis that membrane cholesterol build up constitutes an early phase in tumorigenesis, led us to concentrate on developing an efficient route to compactin, which has been shown to be a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis. As an extension of earlier studies employing bicyclo[2.2.1]heptane chemistry, we plan to prepare stereospecifically, in optically active form, thienamycin and three C(10) analogs [10Beta-fluoro, 10Beta-methyl, and 10Beta-methoxythienamycin.