ASYMMETRIC SYNTHESIS OF MEDIUM RING POLYETHERS

这一新计划将集中于开发一种新的战略，用于复杂的中环醚海洋天然产物的对映选择性合成。实际的不对称羟醛加成，然后是闭环复分解反应将被用来构建六到九元环醚。利用邻氧取代基的Guche效应，可以在不受环限制的情况下，实现中位环的闭环歧化反应。这种影响将在串联开环-闭环复分解反应中探索，以同时生产两个中等尺寸的环醚。中环醚的合成方法将被用于合成各种新型的、具有药理活性的海洋天然产物，如异极烯、泛诺沙林、短杆菌毒素A、粘附素和巨藻毒素。由于许多聚醚毒素和细胞毒性番荔枝内酯的数量很少，化学合成为进一步研究毒素和抗肿瘤药物的作用机制和化学修饰提供了一种解决方案，最终导致公共卫生的改善。

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.