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

Norzoanthamine：将适当官能化的前体用AcOH-H_2O处理，导致串联环合得到双胺结构（CDEFG环片段），这是Norzoanthamine最具特征的片段。对诺佐那敏的全合成进行了研究。从Wieland-Miescher酮或hajo - parrish酮开始，我们能够构建去甲佐那敏的ABC环。我们目前正试图制备一种环化前体以完成全合成。邻苯二甲酸乙酯：我们已经开发了一种新的方法，即氟阴离子催化三甲基硅化α， β-环氧-γ-内酯与醛的醛醇型反应，完成了邻苯二甲酸乙酯的全合成。这种方法的缺点是，副羟基的氧化是合成乙聚辛烷所必需的。然后我们研究了另一种有效的方法来解决这个问题。最后，我们能够通过三甲基硅化α， β-环氧-γ-内酯与酸性氟化物在催化量的氟阴离子存在下的反应开发出一个单步程序。研究发现，除了抑制癌细胞增殖外，乙聚辛烷还能促进癌细胞系（BALL-1细胞）的凋亡。从生物学的角度来看，这些结果非常有趣，我们对鉴定epolactaene的细胞内蛋白靶点特别感兴趣。为此，制备了环氧乙烷分子探针。Akaterpin：我们之前已经证明，Akaterpin的上十碳烷的相对立体化学是一个顺式融合的十碳烷。为了构建双十碳烯结构，我们尝试了烯酮与上十碳烯和乙烯基环己烯的分子间Diels-Alder反应。发现反应以立体选择的方式进行（9:1），并且通过与akaterpin相关发现主要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.