A Direct Aldol Strategy toward B-Type Amphidinolides

描述（由申请人提供）： 氨杂环内酯类化合物是一类复杂的大环内酯类化合物，具有很强的抗肿瘤活性。B-型ampdinolides代表有前途的领导在寻找新的化疗药物。不幸的是，这些化合物，从海洋腰鞭毛虫分离，只能以微量分离。虽然许多研究小组已经开始进行全合成，但目前还没有合成路线。这里提出的一种新的策略调查使用直接羟醛缩合反应促进Trost的新的双锌催化剂。这种aldol反应的独特性质可能使一个顺序的，催化的，不对称的aldol反应的发展。这种连续的羟醛缩合过程将允许存在于B-型两性环内酯中的所需C18-C22三醇部分的快速、立体控制的组装。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。通过闭环复分解的大环化已经成为一种强大的方法，以允许获得否则可能仍然无法获得的分子。出于这个原因，提出通过闭环复分解（RCM）形成难以捉摸的26元大环内酯的amphidinobenzene B1。

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).