Synthetic Investigation on the Structure-Function of Biologically Significant Marine Natural Products

去甲黄胺：用ACoH-H_2O处理适当官能化的前驱体，进行串联环合反应，得到双胺结构(CDEFG环部分)，这是去甲黄胺最具特征的一段。对去甲苯甲胺的全合成也进行了合成研究。从Wieland-Miescher酮或Hajos-Parrish酮出发，我们能够构建去甲苯甲胺的ABC环部分。Epolactaene：我们已经通过开发一种新的方法完成了Epolactaene的全合成，即三甲基硅烷化的α，β-环氧-γ-内酯与醛的Aldol型反应。这种方法的缺点是在合成环己烷时需要对仲羟基进行氧化。然后，我们研究了一种替代的有效方法来解决这个问题。最后，我们通过三甲基硅烷化的α，β-环氧基-γ-内酯与酸性氟化物在催化量的氟离子存在下的反应，开发了一步反应程序。环氧丙烷被发现除了对细胞增殖有抑制作用外，还能促进癌细胞系(BOL-1细胞)的凋亡。从生物学的角度来看，这些结果非常有趣，我们特别感兴趣的是鉴定依波拉坦的细胞内蛋白靶标。为了做到这一点，我们制备了环氧丙烷的分子探针。阿卡特平：我们之前已经证明阿卡特平的上十氢化合物的相对立体化学是顺式融合的十氢化合物。为了构建双十氢化合物结构，我们尝试了烯酮与上十氢化合物和乙烯基环己烯的分子间Diels-Alder反应。该反应以立体选择性的方式进行(9：1)，通过与阿卡特平的关联，发现主要的异构体具有天然的立体化学。

Norzoanthamine : Treatment of appropriately functionalized precursor was treated with AcOH-H_2O resulted in the tandem cyclization to obtain the bisaminal structure (CDEFG ring moiety), a most characteristic segment of norzoanthamine. Synthetic investigation toward a total synthesis of norzoanthamine was also attempted. Starting from Wieland-Miescher ketone or Hajos-Parrish ketone, we were able to construct a ABC ring moiety of norzoanthamine. We are currently trying to prepare a cyclization precursor for completion of the total synthesis.Epolactaene : We have already completed the total synthesis of epolactaene by developing a novel method, that is a fluoride anion-catalyzed aldol type reaction of trimethylsilylated α, β-epoxy-γ-lactone with aldehyde. The drawback of this methodology is that osidation of the secondary hydroxyl group is necessary for the synthesis of epolactane. We then examined an alternative and efficient approach to solve this problem. Finally, we were able to develop a single step procedure by the reaction of trimethylsilylated α, β-epoxy-γ-lactone with acid fluoride in the presence of a catalytic amount of fluoride anion. Epolactane was found to enhance an apoptosis of a cancer cell line (BALL-1 cell) in addition to an inhibitory effect on a cell proliferation. These results are quite interesting from a biological point of view, and we were particularly interested in an identification of an intracellular protein target of epolactaene. In order to do this, molecular probe of epolactaene was prepared.Akaterpin : We have previously shown that the relative stereochemistry of the upper decalin of akaterpin is a cis-fused decalin. In order to construct a bis decalin structure, we attempted an intermolecular Diels-Alder reaction of enone with upper decalin and vinyl cyclohexene. The reaction was found to proceed in a stereoselective manner (9 : 1), and the major isomer was found to have a natural stereochemistry by correlating to akaterpin.