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

halchlorine和pinnaic acid是分别从海绵和冲绳双壳类动物中分离出来的新型海洋天然产物。halchlorin可抑制VCAM-1（血管细胞粘附分子-1）的诱导，而VCAM-1是治疗冠心病的有效靶点。蒎酸是一种磷脂酶A2抑制剂，具有治疗炎症性疾病的潜力。研究了氯-蒎酸螺环核的合成方法。合成方法的关键步骤是通过应用n -酰基亚硝基化合物的分子内反应制备独特的azspiro [4.5]decan骨架，通过立体选择引入乙基将叔丁基二甲基硅氧基乙基引入azspiro [4.5]decan骨架的7位，并将2-羟基-1-甲基乙基片段构建到1位

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