Enantioselective Synthesis of Leustroducsin B

描述（由申请人提供）： 本文提出的项目是天然产物leustroducsin B（1）的方法学和合成研究; leustroducsin B是从钝顶链霉菌培养液中分离的一种有效的集落刺激因子诱导剂。该研究项目将：1）研究通过钯催化的不对称烯丙基烷基化（AAA）合成1，3-二取代的环己烷部分，2）研究使用锌催化的不对称羟醛缩合反应构建1，3-二醇部分的可行性，3）研究催化的不对称[2，3]-Wittig重排并将其应用于α，β-不饱和内酯部分，4）完成天然产物的合成并产生类似物以测试生物活性。leustroducsin B（1）的合成将有助于研究其生物活性，包括诱导集落刺激因子的产生和血小板增多以及增强宿主对大肠杆菌致死性感染的抵抗力。

DESCRIPTION (provided by applicant): The project proposed herein is a methodology and synthetic investigation of the natural product leustroducsin B (1); a potent colony-stimulating factor inducer isolated from the culture broth of Streptomyces platensis. This research project will: 1) investigate the synthesis of the 1,3-disubstituted cyclohexane moiety via a palladium-catalyzed asymmetric allylic alkylation (AAA), 2) study the viability of constructing the 1,3-anf/ diol moiety using a zinc-catalyzed asymmetric aldol reaction, 3) investigate a catalytic, asymmetric [2,3]-Wittig rearrangement and apply it toward the alpha, beta-unsaturated lactone moiety, 4) complete the synthesis of the natural product and produce analogs to test for biological activity. The development of a practical synthesis of leustroducsin B (1) will be beneficial to the investigation of the biological activities that include inducing colony-stimulating factor production and thrombocytosis as well as augmenting host resistance in lethal infection with Escherichia coli.