TUMOR REMISSION--TAXOL AND CLOSE ANALOGS VIA SYNTHESIS

肿瘤缓解——紫杉醇及其类似物的合成

• 批准号: 2105130
• 负责人: LEO A PAQUETTE
• 金额: $ 24.18万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-15 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2105130
• 关键词: analog; antineoplastics; bridged cyclic compound; drug design /synthesis /production; paclitaxel; stereoisomer

DESCRIPTION (adapted from applicant's abstract): This proposal deals with approaches to the total synthesis of taxol using D-camphor as an inexpensive, enantiomerically pure commodity. The strategy is to produce the natural product as well as a series of analog structures which would be accessible by the synthetic route, but not from baccatin III itself. These analogs are deoxytaxol as well as the 3Beta-epimer and analogs based on the 2-deoxy-2,3-dehydro system. The proposal places a great deal of emphasis on joining two ends of the molecule through an organometallic addition reaction and establishing a precursor to the total skeleton via an oxy-Cope rearrangement. When that would be accomplished, it would generate not the ring system of taxol itself, but a structure in which the A ring is 5-membered and the B ring is 9- membered. This in turn necessitates rearrangement to expand the A ring and contract the B ring. Ways to bring that about have been proposed.

描述（改编自申请人摘要）：本提案涉及 以D-樟脑为原料， 便宜的对映体纯的商品。 战略是生产 天然产物以及一系列类似结构， 可以通过合成途径获得，但不能从浆果赤霉素III本身获得。 这些类似物是脱氧紫杉醇以及3 β-差向异构体和类似物 基于2-脱氧-2，3-二氢呋喃系统。 该提案提出了一个伟大的 重点是通过一个连接分子两端的 有机金属加成反应，并建立前体的有机金属， 通过氧代科普重排得到的骨架 当那将是 完成后，它不会产生紫杉醇本身的环系统， 其中A环为5元环且B环为9元环的结构 membered. 这反过来又需要重排来扩大A环 收缩B环。 已经提出了实现这一目标的方法。