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

盐氯碱和羽叶酸分别是从海绵和冲绳双壳贝类中分离得到的新型海洋天然产物。盐氯被证明可以抑制VCAM-1（血管细胞粘附分子-1）的诱导，VCAM-1是治疗冠心病的有效靶点。羽叶酸是磷脂酶A2的抑制剂，具有治疗炎性疾病的潜力。研究者开发了卤代氯和羽叶酸螺环核的合成方法。该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烯化反应制备独特的氮杂螺[4.5]癸烷骨架，通过乙炔基的立体选择性引入，将叔丁基二甲基甲硅氧基乙基部分立体选择性引入到氮杂螺[4.5]癸烷骨架的7-位，并将2-羟基-1-甲基乙基部分构建到1-位上

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