Synthetic Studies of Bioactive Marine Alkaloids Based on Nitroso-Ene Reaction

基于亚硝基烯反应的生物活性海洋生物碱的合成研究

• 批准号: 13672232
• 负责人: AOYAGI Sakae
• 金额: $ 1.86万
• 依托单位: Tokyo University of Pharmacy & Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672232/
• 关键词: marine alkaloids; halichlorine; pinnaic acid; acylnitroso compounds; ene reaction; ピンナ酸類

Halichlorine and pinnaic acid are novel marine natural products isolated from the marine sponge and the Okinawan bivalve, respectively. Halichlorine is shown to inhibit the induction of VCAM-1 (vascular cell adhension molecule-1), a potent target for the treatment and coronary heart disease. Pinnaic acid is an inhibitor of phospholipase A2 that has potential for treatment of inflammatory disease. The investigator has developed the synthesis of the spirocyclic core of halichlorine and pinnaic acid. The key steps in the synthetic approach are the preparation of the unique azaspiro[4.5]decan skeleton through the application of the intramolecular enereacton of the N-acylnitroso compound, stereoselective introduction of the tert-butyldimethylsilyloxy)ethyl moiety to the 7-position of the azaspiro[4.5]decan skeleton through a stereoselective introduction of the ethynyl group, and construction of the 2-hydroxy-1-methylethyl moiety onto the 1-position

卤化氯和品甲酸是分别从海绵和冲绳双壳类中分离得到的新型海洋天然产物。卤化氯被证明可以抑制VCAM-1(血管细胞黏附分子-1)的诱导，VCAM-1是治疗和冠心病的有效靶点。品甲酸是一种磷脂酶A2的抑制剂，具有治疗炎症性疾病的潜力。这位研究人员开发了卤化氯和品甲酸的螺环核心的合成。合成方法的关键步骤是利用N-酰基亚硝基化合物的分子内能合成独特的氮杂螺[4.5]DeCan骨架，通过乙基的立体选择性引入在氮杂螺[4.5]DeCan骨架的7-位上立体选择性地引入(叔丁基二甲基硅氧基)乙基，以及在1-位上构筑2-羟基-1-甲基乙基