ASYMMETRIC SYNTHESIS OF MEDIUM RING POLYETHERS

这个新的计划将集中在复杂的中环醚海洋天然产物的对映选择性合成的新策略的发展。 一个实用的不对称羟醛加成，然后闭环复分解反应将用于构建六至九元环醚。 利用邻位氧取代基的笨拙效应，可以在不受环约束的情况下实现中环的闭环复分解反应。 这种效果将探讨在串联开环闭环复分解反应，同时生产两个中等规模的环醚。 中环醚的合成方法将被用于合成多种新颖的、具有生物活性的海洋天然产物，如异月桂烯、潘诺萨莱烯、短尾藻毒素A、粘蛋白和异藻毒素。由于许多聚醚毒素和细胞毒性番荔枝内酯可以非常小的数量，化学合成提供了一个解决供应问题的进一步研究的作用机制和化学修饰的毒素和抗肿瘤剂，最终导致改善公众健康。

This new program will focus on the development of a novel strategy for the enantioselective synthesis of complex medium ring ether marine natural products. A practical asymmetric aldol addition followed by a ring closing metathesis reaction will be used to construct six to nine membered cyclic ethers. The ring closing metathesis reaction of medium rings can be effected without cyclic constraints by exploiting the gauche effect of adjacent oxygen substituents. This effect will be explored in a tandem ring opening-ring closing metathesis reaction for the simultaneous production of two medium-sized cyclic ethers. The methods for medium ring ether synthesis will be utilized in the synthesis of a variety of novel, pharmacologically active marine natural products such as isolaurallene, pannosallene, brevetoxin A, mucocin and gigantecin. Since many of the polyether toxins and the cytotoxic annonaceous acetogenins are available in very small quantities, chemical synthesis offers one solution to the supply problem for further studies on the mechanism of action and chemical modification of the toxins and antitumor agents, leading ultimately to improvements in public health.