SPECIFICITY IN TERPENE AND STEROL BIOSYNTHESIS

萜烯和甾醇生物合成的特异性

• 批准号: 3268574
• 负责人: ROBERT M. COATES
• 金额: $ 20.49万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3268574
• 关键词: antibiotics; chemical models; cyclization; diterpenes; drug design /synthesis /production; mass spectrometry; molecular rearrangement; nuclear magnetic resonance spectroscopy; pheromone; pyrophosphatase; squalene; stereochemistry; stereoisomer; sterols; terpenes; tritium

Terpenes and sterols manifest a variety of biological functions and activities as hormones, plant regulatory substances, pheromones, antibiotics, and phytoalexins among others. A knowledge of the stereospecificity and mechanisms associated with individual steps in the biosynthetic pathways to them will facilitate the rational design of specific inhibitors or promoters. The objectives of this research are to elucidate the sterochemistry and mechanisms of important reactions involved in terpene and sterol biosynthesis by labelling experiments, by synthesis of potential intermediates, and by investigations with model compounds. Another goal is the synthesis and evaluation of potential inhibitors of key enzymes on the biosynthetic pathways. The specific aims may be summarized as follows: 1. Synthesis of 9,10-syn diterpenes and investigation of the sterochemistry of the cyclizations leading to them as part of the biosynthetic pathway to the momilactone phytoalexins. 2. Stereoselective total synthesis of the cyclobutyl isomer of presqualene as a new intermediate in, or inhibitor or, squalene biosynthesis. 3. Synthesis and evaluation of aza analogs of carbocation intermediates as novel branch-point inhibitors. 4. Elucidation of the complete stereochemistry of the prenylation reaction forming the cis double bonds of dolichol and rubber by means of stereospecific tritium labelling. 5. Synthesis and investigation of bridged phosphates and pyrophosphates as precursors to bidentate carbocation-phosphate ion pairs or as transition inhibitors of mono-and diterpene cyclases. 6. Determination of the stereochemistry and isotope effects of eliminations that terminate enzymatic cyclizations producing enantiomeric monoterpenes.

萜烯和固醇表现出多种生物学功能 以及作为激素，植物调节物质的活动， 信息素，抗生素和植物雷丁素等。 一个 了解相关的立体特异性和机制 在生物合成途径中采用单个步骤将 促进特定抑制剂或启动子的合理设计。 这项研究的目标是阐明 涉及重要反应的静态化学和机制 通过标记实验的萜烯和固醇生物合成，由 潜在中间体的合成，并通过研究 模型化合物。 另一个目标是综合和评估 关键酶对生物合成途径的潜在抑制剂。 具体目的可以总结如下： 1。9,10-Syn二萜的合成和研究 自动化的静态化学导致它们的一部分 Momilactone植物甲状腺素的生物合成途径。 2。环丁基异构体的立体选择性总合成 作为新的或抑制剂的新中间体，或者，propequalene 生物合成。 3。碳化碳酸盐类似物的合成和评估 中间作为新的分支抑制剂。 4。阐明原化的完整立体化学 反应形成多利醇和橡胶的顺式双键 立体特异性tri木标记的手段。 5。桥接磷酸盐和研究的合成和研究 焦磷酸盐作为二齿碳定位磷酸盐的前体 离子对或单萜的过渡抑制剂 循环酶。 6。确定立体化学和同位素的效应 消除终止酶环的消除 对映体单二烯。