TOTAL SYNTHESIS OF THE ANTILEUKEMIC AGENT BRYOSTATIN 1

尽管在很大程度上仍未开发，但海洋已被证明是 几类具有潜在用途的海洋天然产品 药学特性。例如，从植物中分离出的几种化合物 Bugula neritina在某些抗癌测试中表现出了希望，并且 Bryostatin 1，这个小组的代表成员，确实延长了 白血病小鼠的平均寿命提高52-59%。这个项目是专门的 目的是合成26元大环内酯类化合物Bryostatin 1，C47H68O17 具有包含一系列1，2-和1，3-二醇部分的11个手性中心， 吡喃环和烯键。该化合物是逆合成的 被解剖成三个主要片段，将在决赛中组装 拟议合成的各个阶段。因此，整个方案是高度 收敛，从而使合成的实际执行变得实用， 尽管目标分子的结构很复杂。 嵌入在Bryostatin 1中的所有结构单元都可以被构建 通过我们或其他机构最近开发的几种方法 实验室。本课程中将遇到的立体化学问题 将通过适当地应用 这个概念现在被称为多重不对称诱导。这件事的重要性 非环立体化学控制的概念现已得到充分认识。 这一项目的实施无疑将增强我们的综合实力 专业知识和进一步帮助确定尚未解决的新的根本问题 在有机合成领域进行研究。主要的好处是， 然而，将是丰富的信息，可以回答许多 关于苔藓抑素结构/活性关系的问题。它 绝对打算提交足够的这种海洋产品的样品 以及用于生物筛选的其衍生物。

Although still largely untapped, the oceans have proven to be a source of several families of marine natural products possessing potentially useful pharmaceutical properties. For instance, several compounds isolated from Bugula neritina have shown promise in certain anticancer tests, and bryostatin 1, a representative member of this group, indeed extends the average lifetime of leukemic mice by 52-59%. This project is specifically aimed at the synthesis of bryostatin 1, C47H68O17, a 26-membered macrolide with 11 chiral centers comprising a series of 1,2-and 1,3-diol moieties, pyran rings, and olefinic linkages. The compound is retrosynthetically dissected into three major fragments, which will be assembled in the final stages of the proposed synthesis. Therefore, the entire scheme is highly convergent thus rendering the actual execution of the synthesis practical, despite the structural complexity of the target molecule. All of the structural units embedded in bryostatin 1 can be constructed through several methodologies developed recently in our or other laboratories. Stereochemical problems to be encountered during the course of the synthesis will be resolved with the proper application of the concept now termed multiple asymmetric induction. The importance of this concept in acyclic stereochemical control has now been fully recognized. The pursuit of this project will undoubtedly enhance our synthetic expertise and further help identify new fundamental problems yet to be investigated in the field of organic synthesis. Of primary benefit, however, would be the wealth of information which could answer many questions concerning the structure/activity relationship of bryostatin. It is definitely intended to submit adequate samples of this marine product and its derivative for biological screenings.