Total Synthesis of Plocamium Polyhalogenated Monoterpenes, Analogues, and Biologi

描述（由申请人提供）：Plocamium多卤代单萜是首先从红藻Plocamium cartilagineum中分离的代谢物，其特征在于几个不饱和单元以及多个卤素，包括两个连续的立体生成的含氯碳。 这些分子具有广泛的生物活性，但最显著的是对一系列实体瘤癌细胞系显示出细胞毒性。这一有前途的活动引起了威廉·格威克（斯克里普斯海洋研究所）和弗雷德·瓦莱里奥特博士（亨利福特医疗中心）的注意。对Plocamium多卤代单萜家族的几个成员的测试表明只有中等的细胞毒性水平，初步结果表明这些化合物对实体瘤具有选择性，同时对健康细胞保持无毒。然而，由于天然来源的丰度低，这些化合物仅少量分离，无法进行体内研究。加州尔湾大学的Vanderwal小组旨在开发Plocamium多卤代单萜成员的首次合成，所提出的合成是简洁和模块化的，允许合成该类的多个成员，以及许多非天然类似物，仅对该过程进行微小的修改。简化模型系统合成的初步结果是有希望的，一旦完成，Plocamium多卤代单萜天然产物将被合成。通过与Gerwick和Valeriote博士的合作，将对合成的化合物进行生物活性测试，并在已知生物活性成员的情况下继续进行体内研究。

DESCRIPTION (provided by applicant): Plocamium polyhalogenated monoterpenes are metabolites first isolated from the red algae Plocamium cartilagineum, featuring several units of unsaturation, as well as multiple halogens, including two contiguous stereogenic chlorine-bearing carbons. These molecules possess a wide range of biological activity, but most notably show cytotoxicity against a range of solid-tumor cancer cell lines. This promising activity has caught the attention of William Gerwick (Scripps Institution of Oceanography) and Dr. Fred Valeriote (Henry Ford Medical Center). The testing of several members of the Plocamium polyhalogenated monoterpene family suggests only moderate cytotoxicity levels, initial results indicate that these compounds are selective for solid tumors, while remaining nontoxic to healthy cells. However, due to the low abundance from natural sources, these compounds were only isolated in small quantities, and in vivo studies could not be conducted. The Vanderwal group at the University of California Irvine aims to develop the first synthesis of members of the Plocamium polyhalogenated monoterpenes, The proposed synthesis is concise and modular, allowing for multiple members of the class to be synthesized, as well as a host of unnatural analogues, with only minor modifications to the procedure. Initial results on the synthesis of simplified model systems are promising, and once completed, the Plocamium polyhalogenated monoterpene natural products will be synthesized. Through collaboration with Gerwick and Dr. Valeriote, the synthesized compounds will be tested for biological activity, and in the case of known bioactive members, continue in vivo studies.