NOVEL ENZYMATIC APPROACH TO SEMI-SYNTHESIS OF TAXOL

半合成紫杉醇的新酶法方法

• 批准号: 3493140
• 负责人: DAVID C MUCHMORE
• 金额: $ 4.97万
• 依托单位: BEND RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3493140
• 关键词: acetylation; acylation; alkaloids; catalyst; chemical models; chemical reaction; chemical synthesis; cyclic alcohol; drug design /synthesis /production; enzymes; esterification; high performance liquid chromatography; immobilized enzymes; medicinal plants; nonwater solvent; paclitaxel; plant extracts; plants; protective chemical group

DESCRIPTION (Adapted from the Applicant's Abstract): The objective of this project is to determine the feasibility of developing a novel enzymatic process for semi-synthesis of taxol. Taxol is a promising drug for treatment of ovarian and other cancers. However, it is currently available only in limited quantity by extraction from a rare tree; chemical synthesis is difficult and impractical. This limited availability has prevented wide-scale clinical testing for efficacy against many types of cancer. In this Phase I program,the investigators will investigate the use of enzymes to produce taxol by coupling the taxol side-chain to a taxol precursor, which is readily obtainable from ornamental shrubs. This coupling, or acylation, step is the most difficult step in the semi-synthesis of taxol from its precursor. If the results of Phase I are promising, then efforts in Phase II will be aimed at incorporating this step into synthesis schemes for taxol, as well as developing enzymatic approaches to other key steps in the semi-synthesis of taxol. This program could lead to commercially economical production of taxol, enabling clinical studies for other cancers to be undertaken with taxol while providing sufficient quantities for treatment of cancer patients.

描述(改编自申请人的摘要)：目标 这个项目是为了确定开发一种新的 半合成紫杉醇的酶法工艺。紫杉醇是一种很有前途的药物 用于治疗卵巢癌和其他癌症。不过，目前 只有从稀有树木中提取的限量产品； 化学合成既困难又不切实际。这是有限的 可获得性阻碍了大规模的疗效临床测试 对抗多种癌症。在这个第一阶段的项目中，调查人员 将研究使用酶通过偶联紫杉醇来产生紫杉醇 紫杉醇前体的侧链，可从 观赏灌木。这种偶联，或者说酰化，是最 从紫杉醇的前体半合成紫杉醇的困难步骤。如果 第一阶段的结果是有希望的，那么第二阶段的努力将是目标 将这一步骤纳入紫杉醇的合成方案，以及 开发半合成中其他关键步骤的酶促方法 紫杉醇。这项计划可能导致商业上经济的生产。 紫杉醇，使其他癌症的临床研究得以进行 使用紫杉醇，同时提供足够数量的癌症治疗 病人。