ENANTIOSELECTIVE SYNTHESIS OF WELWISTATIN

韦尔维他汀的对映选择性合成

• 批准号: 6070473
• 负责人: ALEXANDER R HURD
• 金额: $ 3.09万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-03 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6070473
• 关键词: Cyanophyta; alkaloids; antineoplastics; biological products; cyclization; cytotoxicity; drug design /synthesis /production; microtubules; molecular rearrangement; multidrug resistance; stereochemistry

DESCRIPTION The welwitindolinone class of natural products were recently isolated from cyano-bacterial sources and show promise for the treatment of multi-drug resistant tumor cells. Some members of this class of compounds exhibit chemoresistance reversing activities below toxic doses. Other members, including welwistatin, are cytotoxic agents which act by inhibiting microtuble formation in both drug sensitive and multi- drug resistance tumor cells. This proposal outlines an enantioselective synthesis of welwistatin as a representative member of this class of compounds exhibit chemoresistance reversing activities below toxic doses. Other members, including welwistatin, are cytotoxic agents which act by inhibiting microtuble formation in both drug sensitive and multi- drug resistance tumor cells. This proposal outlines an enantioselective synthesis of welwistatin as a representative member of this class of compounds. The key step in the synthesis is a novel Lewis acid catalyzed enamine cyclization-Pinacol rearrangement which simultaneously assembles the bicyclic core and installs the critical quaternary bridgehead center.

描述最近从氰基 - 细菌来源分离出韦尔维替丁酮类别的天然产物，并显示出对多药耐药性肿瘤细胞治疗的希望。这类化合物的一些成员表现出低于有毒剂量的化学抗性逆转活动。其他成员，包括韦尔维斯汀，是细胞毒性剂，它们通过抑制药物敏感和多耐药性肿瘤细胞中的微偶联形成而起作用。该提案概述了韦尔维斯汀作为该类化合物的代表成员的对映选择性合成，表现出低于有毒剂量的化学抗性逆转活动。其他成员，包括韦尔维斯汀，是细胞毒性剂，它们通过抑制药物敏感和多耐药性肿瘤细胞中的微偶联形成而起作用。该提议概述了韦尔维斯汀作为该类化合物的代表成员的对映选择性合成。合成的关键步骤是一种新型的刘易斯酸催化的谜环化pinacol重排，同时组装了双环芯并安装了关键的Quaternary Bridgehead Center。