IRON COMPLEXES TO POLYENE SYNTHESIS

我们研究的唯一目标是开发新的合成材料 以立体专一性方式构建C-C键的方法。 具体地说，我们希望利用三酮基团的能力 [Fe(CO)3]至： A)控制共轭双键的立体化学； B)保护和稳定不稳定和高度共轭的系统； C)控制相邻不对称中心的相对立体化学 并且远离配位的二烯。 作为演示这一方法的工具，我们选择了 大乳酸菌素A、原霉素内酯IV和Ambrticin AS的C9-Cl6片段 目标。 大乳酸菌素A是一种24元环状多烯内酯，分离自 分类学上未鉴定的深海细菌。该化合物在 抑制单纯疱疹病毒(I和II，约7微克/毫升水平)和 保护T淋巴细胞免受人类免疫抑制病毒(HIV)感染 复制(10微克/毫升水平)。这种化合物的结构是 通过光谱和降解研究确定。 这种细菌的发酵已被证明是不可靠的，因此 大量的大分子乳酸素A是不可用的。 原霉素内酯IV是一种16元环状多烯内酯，具有 对革兰氏阳性菌的抗生素特性。AmBruticin是一种 从多角藻发酵提取液中分离出的多烯 纤维变种弗鲁姆。它在体内展示了前所未有的口服 抗系统性真菌感染、组织胞浆菌病和 球孢子菌病。

The lone range goal of our research is to develop new synthetic methodology for the construction of C-C bonds in a stereospecific fashion. In particular, we wish to utilize the ability of a tricarbonyliron adjunct [Fe (CO)3] to: a) to control the stereochemistry of conjugated double bonds; b) to protect and stabilize labile and highly conjugated systems; c) to control the relative stereochemistry at asymmetric centers adjacent and remote to the coordinated diene. As vehicles for demonstration of this methodology, we have chosen macrolactin A, protomycinolide IV and the C9-Cl6 segment of ambruticin as targets. Macrolactin A is a 24-membered cyclic polyene lactone isolated from a taxonomically unidentified deep sea bacterium. This compound is active in inhibiting Herpes simplex viruses (I and II, ca. 7 ug/mL level) and in protecting T-lymphoplast cells against human immunosuppressive virus (HIV) replication (10 ug/mL level). The structure of this compound was determined via means of spectroscopic and degradation studies. Fermentation of this bacterium has proved to be unreliable, and thus larger quantities of macrolactin A are not available. Protomycinolide IV is a l6-membered cyclic polyene lactone possessing antibiotic properties against Gram positive bacteria. Ambruticin is a polyene impound isolated from the fermentation extracts of Polyangium cellulosum var. fulvum. It has exhibited unprecedented oral in vivo activity against systemic fungal infections histoplasmosis and cocidiomycosis.