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: 2008491
• 负责人: LEO A PAQUETTE
• 金额: $ 25.17万
• 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/2008491
• 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