A Direct Aldol Strategy toward B-Type Amphidinolides

B 型氨脒内酯的直接羟醛策略

基本信息

批准号：
6937935
负责人：
BRANDON TURUNEN
金额：
$ 4.21万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2008-09-29
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The amphidinolides are a family of complex macrolides exhibiting potent and unique antitumor activity. The B-type amphidinolides represent promising leads in the search for new chemotherapeutic agents. Unfortunately, these compounds, isolated from marine dinoflagellates, are only isolable in minute quantities. Although many groups have pursued their total synthesis, no synthetic route currently exists. A novel strategy proposed here investigates the use of the direct aldol reaction promoted by Trost's new dizinc catalysts. The unique nature of this aldol reaction may make possible the development of a sequential, catalytic, asymmetric aldol reaction. This sequential aldol process would allow for rapid, stereocontrolled assembly of the required C18-C22 triol moiety present in the B-type amphidinolides. Formation of the required 26-member macrolide has represented a formidable challenge for previous investigators. Macrocyclization via ring closing metathesis has emerged as a powerful method to allow access to molecules which otherwise may have remained unattainable. For that reason, it is proposed to form the elusive 26-member macrolide of amphidinolide B1 via ring closing metathesis (RCM).

描述（由申请人提供）：两栖内酯类是一类复杂的大环内酯类化合物，具有有效且独特的抗肿瘤活性。 B 型氨吡啶内酯代表了寻找新化疗药物的有希望的先导者。不幸的是，这些从海洋甲藻中分离出来的化合物只能少量分离。尽管许多研究小组已经进行了全合成，但目前尚不存在合成路线。这里提出的一种新策略研究了由 Trost 的新型二锌催化剂促进的直接羟醛反应的使用。这种羟醛反应的独特性质可能使得连续、催化、不对称羟醛反应的发展成为可能。这种连续的醇醛缩合过程将允许快速、立体控制地组装 B 型两栖内酯中所需的 C18-C22 三醇部分。所需的 26 元大环内酯的形成对以前的研究人员来说是一个巨大的挑战。通过闭环复分解进行的大环化已成为一种强大的方法，可以获取原本可能无法获得的分子。因此，建议通过闭环复分解 (RCM) 形成难以捉摸的 26 元大环内酯 Amphidinolide B1。