PRACTICAL SYNTHESIS OF THE ANTIHIV AGENT MICHELLAMINE B

作为国家癌症研究所发起的一项倡议的结果 从天然来源的生物碱中发现新的抗HIV药物 米歇尔胺B于1991年被发现。米歇尔胺B表现出广泛的抗药性 HIV对HIV-1、HIV-2及部分耐药株的作用 病毒的特征。尽管它的分离是在12月份才有报道的， 1991年，米歇拉明B目前处于晚期临床前开发阶段(他因此- 称为DNIIA阶段)。 米歇尔胺B是从喀麦隆生长的一种藤本植物中分离出来的。 需要大量资金才能继续对其进行评价 发展。 这个项目有两个主要目标。第一个是发展 一小步(距离现成的起始材料大约十步)， 可大量提供米歇拉明B的实用合成方法 数量(最初是几十克，最终要多得多)。这个 第二个主要目标是利用这种合成来制备两种类似物 对于结构活性关系(SAR)的研究，也是有目的的 生产出效果和/或效力比 米歇拉明B。

As a result of a National Cancer Institute-sponsored initiative to discover novel anti-HIV agents from natural sources, the alkaloid michellamine B was identified in 1991. Michellamine B shows broad anti- HIV activity against HIV-1 and HIV-2 as well as some resistant strains of the virus. Although its isolation was only reported in December, 1991, michellamine B is now in advanced preclinical development (he so- called DNIIA stage). Michellamine B was isolated from a vine that grows in Cameroon. Substantial quantities are required for its continued evaluation and development. This project has two main objectives. The first is the development of a short (ca. ten steps from readily available starting materials), practical synthesis capable of furnishing michellamine B in substantial quantities (initially tens of grams, ultimately considerably more). The second major objective is to use that synthesis to prepare analogs both for structure activity relationship (SAR) studies, but also with the goal of producing analogs with better efficacy and/or potency than michellamine B.