Total synthesis of Zoanthamine

佐安他明的全合成

• 批准号: 6585462
• 负责人: FATIMA R RIVAS
• 金额: $ 2.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-05 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6585462
• 关键词: alkaloids; analog; antiinflammatory agents; aquatic organism; biological products; chemical synthesis; combinatorial chemistry; drug design /synthesis /production; organic chemicals; osteoporosis; predoctoral investigator; skeletal disorder chemotherapy

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.

描述（由申请人提供）：我们的目标是开发可行的合成程序，该程序可以产生Zoanthamine和该生物碱家族的其他成员，例如Norzoanthamine，以简洁的方式。这些生物碱大多数都具有高度功能化的反式蛋白酶和杂环氨基环系统，以及至少三个Quaternary手性中心（Zoanthamine的C-9，C-12，C-12，C-22）。发现Zoanthamine及其亲戚在模型系统中抑制醋酸凤梨菌诱导的炎症。发现Norzoanthamine抑制p388鼠白血病细胞培养物的生长。此外，Norzoanthamine抑制了IL-6产生。 最近，据报道，Zoanthamine型生物碱抑制了骨体重的减少。 Zoanthamine核心的构建将使我们有望开发其类似物的库，以进一步研究其作为骨质疏松药物和/或抗炎药的候选者的潜力。