LABELLED MARINE ANTITUMOR PROMOTERS

拟议研究的长期目标是确定 一种非常有效的抗肿瘤药物--肌醇A的作用机制 促进剂，以及相关的胶膜天然产物。化合物 具有抗肿瘤促进活性对 了解涉及到的早期生化步骤 致癌。这项研究要求大量的 是否有氚材料，以便确定：(A)是否 抗肿瘤启动子与肿瘤启动子化学结合；(B) 抗肿瘤启动子是否能作用于非肿瘤器官 皮肤；(C)它是否在任何器官中蓄积以及它是如何积聚的 代谢；(D)是否与特定的抗肿瘤受体结合 发生了。拟议研究的最终目标是 膜抗肿瘤特异性受体的分离 推动者。自从人类癌症的治疗开始 在观察肿瘤后，当疾病处于 高级阶段和难以控制，了解 抗肿瘤促进剂的作用机制可能使 合理的癌症预防是可能的。 含氚抗氧剂的化学合成策略 肿瘤促进剂利用远程不对称诱导。 分子力学计算已经被执行到 确定关键字的最小能量结构 中间体。最初形成的立体中心将用于 影响所有后续步骤的立体化学。一个 然后通过控制对映体选择性合成是可能的 只对最初形成的分子进行绝对立体化学 立体中心。这导致了更短和更高效的 综合。

The long-term goal of the proposed research is to determine the mode of action of sarcophytol-A, a very active anti-tumor promoter, and of related cembrane natural products. Compounds with anti-tumor promoting activity are important for understanding the early biochemical steps involved with carcinogenesis. This study requires that substantial quantities of tritiated material be available in order to determine: (a) whether the anti-tumor promoter chemically binds the tumor promoter; (b) whether the anti-tumor promoter can act on organs other than the skin; (c) whether it accumulates in any organs and how it is metabolized; (d) whether binding to specific anti-tumor receptors takes place. The ultimate goal of the proposed research is the isolation of the specific receptor for the cembrane anti-tumor promoters. Since the treatment of human cancers is initiated after the observation of tumors, when the disease is at an advanced stage and is difficult to control, an understanding of the mechanism of action of the anti-tumor promoters may make rational prophylaxis against cancer possible. The strategy for the chemical synthesis of the tritiated anti- tumor promoter makes use of remote asymmetric induction. Molecular mechanics calculations have been performed to determine the minimum energy structures for the key intermediates. The initially formed stereocenters will be used to influence the stereochemistry of all subsequent steps. An enantioselective synthesis is then possible by controlling the absolute stereochemistry only of the initially formed stereocenters. This results in a shorter and more efficient synthesis.