Enantioselective Synthesis of Halogenated Chamigrenes

描述（由申请人提供）：最近从Laurencia红藻属中分离出了几种结构有趣的卤代chamigrene倍半萜。由于天然可用性低，对这类细胞毒性毒菌的全面测试受到限制。本文提出了第一个对映选择性全合成的马莲酮及其衍生物。关键的转化将涉及一个不对称的分子内Heck反应，以产生高水平的对映选择性的季碳立体中心。6,6-螺环全碳核将由这种环化产生。在Heck反应中，需要改进反应条件以达到期望的对映体选择性水平。由于分子中剩余的立体中心来自于对四元立体中心的立体控制，因此使用手性催化剂可以获得天然产物的两种对映体。该合成策略将允许从后期中间体合成新的chamigrene衍生物。

DESCRIPTION (provided by applicant): Several structurally interesting halogenated chamigrene sesquiterpenes have recently been isolated from the red algal genus Laurencia. Due to the low natural availability, full testing of this family of cytotoxic chamigrenes has been limited. Proposed here is the first enantioselective total synthesis of ma'ilione and its derivatives. The key transformation will involve an asymmetric intramolecular Heck reaction to generate the quaternary carbon stereocenter in high levels of enantioselectivity. The 6,6-spirocyclic all carbon core will result from this cyclization. Development of reaction conditions will be required to achieve desired levels of enantioselectivity during the Heck reaction. Since the remaining stereocenters in the molecule arise from steric control of the quaternary stereocenter, use of a chiral catalyst provides access to both enantiomers of the natural product. The synthetic strategy will allow new chamigrene derivatives to be synthesized from late stage intermediates.