ASYMMETRIC SYNTHESIS OF MEDIUM RING POLYETHERS

这个新项目将重点开发一种对映选择性合成复杂介质环醚海洋天然产物的新策略。一个实际的不对称醛醇加成后的合环复合反应将被用来构造六至九元环醚。利用邻氧取代基的间扭式效应，可以在不受环约束的情况下实现介质环的合环复分解反应。在同时生产两种中型环醚的串联开环-闭环复分解反应中探讨了这种效应。中环醚的合成方法将被用于合成各种新颖的、具有药理活性的海洋天然产物，如异aurallene、pannosalene、brevetoxin a、mucocin和gigantecin。由于许多聚醚毒素和细胞毒性无机乙酰原素的数量非常少，化学合成为进一步研究毒素和抗肿瘤剂的作用机制和化学改性提供了一种解决供应问题的办法，最终改善公众健康。

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.