ENANTIOSELECTIVE APPROACH TO ANTITUMOR AGENTS

化学合成聚四氟乙烯的立体选择性方法 与细胞毒素亚单位相对应的吡喃环系统 海洋天然产物冈田酸(1)和延胡索乙素B(2) 分离自海绵Halichondria okadia Kadora是 描述。 化学合成(+)-的对映选择性方法 从植物中分离出的一种有效的细胞毒剂--倍半胺A(3) 田菁籽提取物和6个结构相关的化合物 提出了类似物的概念。3的类似物，对应于 将制备B-环和C-环的结构修饰，并 被评估为潜在的细胞毒剂。抗肿瘤药物概况 活动与结构变化将在努力中发展 将细胞毒性与结构特征的差异联系起来。 B环类似物的设计是基于这种方法 TO-3是对映体发散性的，允许制备这两个 对极。C环类似物的设计是为了尝试 增加四氢呋喃环的化学稳定性 含有不稳定的半缩醛。该方法基于 含氯氧烯丙基硅烷作为双官能团的可能性 碳亲核试剂。番泻亚胺的化学合成 结构的设计是基于同手性C_1- 含氧烯丙基硅烷将参与与 构型稳定的手性醛，SP3杂化，α- 用于光学构筑的烷氧基烯丙基阴离子当量 激活的1，2-二醇单元。聚合吡喃的合成方法 冈田酸和延胡索乙素B的亚基是基于 1-氧代烯丙基硅烷和E-巴豆基硅烷的功能 立体选择性引入的高烯醇类等价物 捕获生成的氧离子所产生的丙醛当量 在吡喃或呋喃环上。

A stereoselective approach to the chemical synthesis of fused pyran ring systems corresponding to subunits of the cytotoxic marine natural products okadaic acid (1) and halichondrin B (2) isolated from the sea sponge Halichondria okadia Kadora is described. An enantioselective approach to the chemical synthesis of (+)- sesbanimide A (3), a potent cytotoxic agent isolated from plant extracts of Sesbania drummundii seed, and six structurally related analogues is proposed. Analogues of 3, that correspond to structural modifications of the B- and C-rings will be prepared and evaluated as potential cytotoxic agents. A profile of antitumor activity versus changes in structure will be developed in an effort to correlate cytotoxicity with differences in structural features. The B-ring analogues were designed on the basis that the approach to 3 is enantiodivergent and allows for the preparation of both antipodes. The C-ring analogues are designed in an attempt to increase the chemical stability of the tetrahydrofuran ring which contains a labile hemiacetal. The approach is based on the potential for C1-oxygenated allylsilanes to behave as bifunctional carbon nucleophiles. The chemical synthesis of the sesbanimide structures is designed on the expectation that homochiral C1- oxygenated allylsilanes will participate in addition reactions with chiral aldehydes as configurationally stable, sp3 hybridized, alpha- alkoxy allyl anion equivalents for the construction of optically active 1,2-diol units. The synthetic approach to the fused pyran subunits of okadaic acid and halichondrin B is based on the ability of C1-oxygenated allylsilanes and E-crotylsilanes to function as homoenolate equivalents for the stereoselective introduction of a propionaldehyde equivalent by traping an oxonium ion generated on a pyran or furan ring.