STEREOCHEMISTRY OF POLYKETIDE BIOSYNTHESIS

聚酮生物合成的立体化学

• 批准号: 6220431
• 负责人: HIROMI MORIMOTO
• 金额: $ 0.95万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6220431
• 关键词: biomedical resource; building /facility design /renovation; education; technology /technique

Polyketides are a diverse group of natural products which include many compounds useful as drugs. They are assembled by condensation of acetate/malonate units followed by a variety of subsequent modifying reactions. The mechanism of the initial cyclization is still incompletely understood. This project addresses various aspects of polyketide biosynthesis including the steric course of the initial condensation reaction. This will be studied using stereospecifically 13C and 3H-labelled malonic acid of R and S configuration. This compound will be synthesized from an appropriately 13C-labelled precursor, epoxysuccinic acid, by opening of the epoxide ring with supertritide, followed by permanganate oxidation to malonate. The resulting malonate samples will be used to determine the overall stereochemical course of the formation of the polyketides, 6-methylsalicyclic acid and orsellinic acid and the chalcone, naringenin. The results will give insight into the chemical mechanism of this key carbon-carbon bond forming process. In addition, in a collaboration with the group of Professor Yu Sam Kim, Seoul, we will study the stereochemistry of malonate metabolism by several microbial enzymes. User Details: Experiment Details: User Number: 1614 Tritiation City, State: Seattle, WA NMR Funding Source: NIH 5 R01 AI 20264-16 Tritides and NSF INT-9604888 2 days Charge: $4188.59 2 compounds Program Income: $4187.89 Secondary User: Professor Yu Sam Kim Seoul, North Korea

聚酮类化合物是一类不同的天然产物，包括 许多化合物可作为药物使用。它们是通过冷凝的 乙酸酯/丙二酸单元，然后进行各种后续改性 反应。初始环化的机理仍然是 不完全理解。这个项目涉及到以下各个方面 聚酮的生物合成包括最初的立体过程 缩合反应。这将使用立体特异地进行研究 ~(13)C和~3H标记的R和S构型的丙二酸。这 化合物将由适当标记的13C合成 前体，环氧丁二酸，通过与 超三聚体，然后高锰酸盐氧化成丙二酸酯。这个 产生的丙二酸样本将被用来确定总体 聚酮形成的立体化学过程， 6-甲基水杨酸、香豆酸和查尔酮， 柚皮苷元。这一结果将有助于深入了解其化学机制。 这一关键的碳-碳键形成过程。此外，在 与首尔的金宇森教授团队合作，我们将 几种微生物对丙二酸代谢的立体化学研究 酵素。用户详细信息：实验详细信息：用户编号：1614 Tritiation City，State：西雅图，华盛顿州核磁共振资金来源：NIH 5 R01 AI 20264-16三重天和国家科学基金会INT-9604888 2天费用：4188.59美元2 复合课程收入：4187.89美元二级用户：于三教授 金首尔，朝鲜