Total synthesis of Zoanthamine

描述(由申请人提供)：我们的目标是开发一种可行的合成方法，能够以简明的方式产生佐安他明和这个生物碱家族的其他成员，如去甲基安非他明。这些生物碱大多具有高度官能化的反式十一酮和杂环氨基环体系，以及至少三个四元手性中心(花色胺的C-9、C-12、C-22)。在一个模型系统中，佐安他明及其类似物被发现能抑制佛波醇肉豆蔻酸酯引起的炎症。去甲苯甲胺对培养的P388小鼠白血病细胞有生长抑制作用。此外，去甲苯甲胺还能抑制IL-6的产生。最近，有报道称，黄嘌呤类生物碱可抑制骨重的下降。该核心的构建将引导我们开发一个类似物的文库，以进一步研究它们作为骨质疏松症药物和/或抗炎药物的候选药物的潜力。

DESCRIPTION (provided by applicant): Our goal is to develop a feasible synthetic procedure that can yield Zoanthamine and other members of this alkaloid family such as norzoanthamine in a concise manner. Most of these alkaloids possess highly functionalized trans-decalone and heterocyclic aminal ring system along with at least three quaternary chiral centers (C-9, C-12, C-22 for zoanthamine). Zoanthamine and its relatives were found to inhibit phorbol myristate acetate induced inflammation in a model system. Norzoanthamine was found to inhibit the growth of P388 murine leukemia cell cultures. In addition, norzoanthamine inhibits IL-6 production. Recently, it has been reported that zoanthamine-type alkaloids suppress the decrease in bone weight. The construction of the core of zoanthamine will lead us to hopefully develop a library of its analogs to further study their potential as candidates for an osteoporotic drug and/or an anti-inflammatory drug.