IRON COMPLEXES TO POLYENE SYNTHESIS

铁络合物到多烯的合成

• 批准号: 2181546
• 负责人: William A Donaldson
• 金额: $ 12.22万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2181546
• 关键词: alkylation; antibiotics; antifungal agents; chemical condensation; chemical synthesis; drug design /synthesis /production; iron compounds; lactones; metal complex; polyenes; stereochemistry

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.

我们研究的唯一范围目标是开发新的合成 以立体特定方式构建C-C键的方法。 特别是，我们希望利用三卡龙骨辅助的能力 [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系统； c）控制邻近不对称中心的相对立体化学 并遥控到协调的狄内。 作为演示这种方法的车辆，我们选择了 大元素A，氨基甲醇IV和AS氨酰蛋白的C9-CL6段AS 目标。 大元素A是从A分离的24元元循环多烯内酯 分类未鉴定的深海细菌。 该化合物活跃 抑制单纯疱疹病毒（i和ii，ca。7ug/ml水平）和 保护T-淋巴结细胞免受人类免疫抑制病毒（HIV） 复制（10 ug/ml水平）。 该化合物的结构是 通过光谱和降解研究确定。 事实证明，该细菌的发酵是不可靠的，因此 不可用大量的大分裂素A。 原霉菌IV是具有L6元的循环多烯内酯，具有 针对革兰氏阳性细菌的抗生素特性。 Ambruticin是A。 多烯蓄积是从聚血管的发酵提取物中分离出来的 纤维素富尔沃。 它在体内表现出前所未有的口服 针对全身真菌感染的活性组织肿瘤病和 Cocidiomycisis。