SYNTHESIS OF SALICYLIHALAMIDE A

水杨酰卤酰胺A是一种新的，高效的（GI 50 = 7 +/- 2 nM的黑色素瘤细胞系），细胞毒性大环内酯从海洋海绵Haliclona sp.上的测试这种化合物的分离表明一种新的作用机制的可能性不同于已知的细胞毒性化合物。发展水杨卤酰胺A及其结构相关的天然或非天然类似物的聚合合成对于研究这类化合物的作用机制至关重要。这些化合物的制备可以帮助开发新的癌症化疗剂。考虑到生物学意义，提出了水杨卤酰胺的收敛合成计划。这些措施包括探索就业的一种新的方法，烯基硼酸酯栓环闭合复分解。该方法通过提供控制产物烯烃的立体化学的方法，将是现有烯烃复分解反应的有价值的扩展。通过使用这种方法提出的合成是通用的，足以提供不仅水杨卤酰胺A本身，而且其结构相关的化合物。

Salicylihalamide A is a novel, highly potent (GI50 = 7 +/- 2 nM for melanoma cell lines), cytotoxic macrolide isolated from the marine sponge Haliclona sp. The testing on this compound suggests the possibility of a novel mechanism of action different from the known cytotoxic compounds. It is crucial for the study of the mechanism of action of this class of compounds to develop convergent syntheses of salicylihalamide A and its structurally related natural or non-natural analogues. Preparation of these compounds may aid the development of novel cancer chemotherapeutic agents. With the biological implications in mind, convergent synthetic plans for salicylihalamide are proposed. These include exploratory employment of a novel methodology, alkenylboronate tethered ring closing metathesis. This methodology will be a valuable extension on the existing olefin metathesis reaction by providing a way to control stereochemistry of the product olefin. The synthesis proposed by using this methodology is versatile enough to provide not only salicylihalamide A itself, but also its structurally related compounds.