NATURALLY OCCURRING POLYENES VIA ORGANOMETALLICS

通过有机金属学天然存在的多烯

• 批准号: 6627163
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 14.87万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627163
• 关键词: alkenes; antiAIDS agent; antifungal agents; biological products; catalyst; charcoal; chemical conjugate; chemical synthesis; macrolide antibiotics; michellamine; nickel; organometallic compounds; polyenes; protective chemical group; stereochemistry; vancomycin

Naturally occurring compounds consisting of multiple olefinic sites occupy a special niche among physiologically active agents. Included in this polyene group are (1) the polyene macrolide antibiotics, clinically valued as anti-fungals. The ion channel-forming materials usually contain between four and seven E-olefins in a conjugated array. The use of conjunctive reagents for rapidly preparing oxo tetra- to heptaene subsections in stereochemically homogeneous form is to be pursued; (2) new routes to biaryls bearing axial chirality, in particular the biaryl portions of vancomycin and michellamine B, will be studied. The former is one of the world's last lines of defense against certain bacterial infections, and the latter is an especially effective anti-AIDS compound. Both targets will derive from an intra-molecular biaryl coupling strategy via organometallic intermediates. Stereoinduction will be controlled by the nature of the tether joining the individual aryl components. Thus, this application discusses not only considerable published progress made during the currant grant period, but extensive unpublished data in support of both the continuing and especially, the new directions in our polyene program, outlined herein. In amines, and (b) nickel-on-charcoal as an effective, inexpensive and environmentally benign catalyst for effecting C-C band formations which should assist us in reaching our goals, and provide general utility as well to the synthetic community.

由多个烯烃位点组成的自然存在的化合物在生理活性剂中占据了特殊的细分市场。该多烯基团包括（1）多烯大花环抗生素，在临床上被视为抗真菌剂。离子通道形成的材料通常在共轭阵列中包含四到七个e-烯烃。要使用结合性试剂快速制备以立体化学上均匀形式的氧二烯二烯类探测； （2）将研究带有轴向手性的新途径，尤其是万古霉素和米其胺B的双子座部分。前者是世界上对某些细菌感染的最后防御措施之一，后者是一种特别有效的抗艾滋病。这两个靶标将通过有机金属中间体衍生出分子内的双轴偶联策略。立体诱导将由连接各个芳基成分的系绳的性质控制。因此，本申请不仅讨论了在醋栗赠款期间取得的大量公开进展，而且还讨论了广泛的未发表数据，以支持继续概述的持续数据，尤其是我们的波利恩计划中的新方向。在Amines和（b）镀镍作为有效，廉价且环保的催化剂，用于影响C-C乐队的形成，这应该有助于我们实现我们的目标，并为合成社区提供通用效用。