Synthesis of Tumor Inhibitory Marine Natural Products

将进行聚酮类和二萜类若干海洋天然产物的全合成。目标化合物对各种人类肿瘤细胞株表现出高度的生长抑制作用，但它们通常不容易从自然来源获得，其数量与它们作为候选药物的评估相符。此外，我们将合成一些更有活性的化合物的类似物，底特律约瑟芬·福特癌症中心的F.Valeriote教授将测试这些化合物对肿瘤和正常人类细胞株的不同细胞毒性。要解决的主要化学问题包括通过手性有机金属化学来控制立体化学，以及设计新的和有效的路线来获得结构新颖的天然产物。

The total synthesis of a number of marine natural products in the polyketide and diterpene families will be undertaken. The targeted compounds exhibit high levels of growth inhibition against various human tumor cell lines but they are generally not readily available from natural sources in quantities amenable to their evaluation as drug candidates. In addition, we will synthesize analogues of some of the more active compounds that will be tested for differential cytotoxicity against tumor vs. normal human cell lines by Professor F. Valeriote at the Josephine Ford Cancer Center in Detroit. The main chemical issues to be addressed include the control of stereochemistry by means of chiral organometal chemistry and the design of new and efficient routes to structurally novel natural products.