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

去甲虫胺：将适当官能化的前体用AcOH-H_2 O处理，导致串联环化，得到双缩醛结构（CDEFG环部分），这是去甲虫胺最具特征的片段。并对去甲虫胺的全合成进行了探索。从Wieland-Miescher酮或Hajos-Parrish酮开始，我们能够构建去甲虫胺的ABC环部分。我们目前正在尝试制备一种环化前体来完成全合成。环己内酯：我们已经完成了环己内酯的全合成，开发了一种新的方法，即氟阴离子催化的三甲基硅烷化α，β-环氧-γ-内酯与醛的羟醛缩合反应。该方法的缺点是仲羟基的氧化对于合成依泊烷是必需的。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，我们能够通过三甲基甲硅烷基化的α，β-环氧-γ-内酯与酰氟在催化量的氟阴离子存在下的反应来开发一个单步程序。发现除了对细胞增殖的抑制作用之外，依泊拉坦还增强癌细胞系（BALL-1细胞）的凋亡。从生物学的角度来看，这些结果是非常有趣的，我们特别感兴趣的是确定一个细胞内的蛋白质目标的epolactaene。Akaterpin：我们以前已经证明Akaterpin的上十氢萘的相对立体化学是顺式稠合十氢萘。为了构建双十氢萘结构，我们尝试了烯酮与上十氢萘和乙烯基环己烯的分子间Diels-Alder反应。发现该反应以立体选择性方式（9：1）进行，并且通过与Akaterpin相关发现主要异构体具有天然立体化学。

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.