Asymmetric Total Synthesis of Octalactins A, B and Their Analogues

Octalactins A和B是1991年从海洋细菌Streptomycessp.中分离得到的两个化合物，它们的结构中含有一个不寻常的中等大小的饱和内酯部分，并且Octalactin A对某些肿瘤细胞具有较强的细胞毒活性。以2-甲基-6-硝基苯甲酸酐（MNBA）和DMAP为原料合成了一个八元环，通过烯酮甲硅烷基缩醛与醛的对映选择性羟醛缩合反应，合成了一个具有光学活性的线性内酯前体和一个具有光学活性的八元环内酯侧链。96 h后，首次采用S-Py酯法合成了六元环内酯;然而，在用银盐催化剂回流的甲苯中，内酯化反应进行缓慢。此外，当反应在室温下进行时，根本不产生目标环化分子。另一方面，在室温下，用MNBA和DMAP有效地促进了开环酸的环化反应，以84%的产率得到了所需的八元环内酯，并且没有产生相应的二萜。中等大小的环内酯部分的构建。

Octalactins A and B were isolated from the marine bacterium Streptomyces sp. in 1991.The structure of these compounds includes an unusual saturated medium-sized lactone moiety, and octalactin A exhibits a potent cytotoxic activity against some tumor cell lines.A method for the synthesis of octalactins A and B is established via a new and quite effective mixedanh ydride lactonization for, the synthesis of an eight-membered ring moiety using 2-methyl-6-nitrobenzoic anhydride (MNBA) with DMAP.Both an optically active linear precursor of the lactone and a side chain of octalactins are prepared by the enantioselective aldol reaction of ketene silyl acetals with aldehydes.The desired 8-membered ring lactone was first synthesized by S-Py ester method after 96 h ; however, the lactonization sluggishly proceeded in refiuxed toluene with the silver salt catalyst.Furthermore, the target cyclized molecule was not produced at all when the reaction was carried out at room temperature.On the other hand, the cyclization reaction of the seco acid was efficiently accelerated by MNBA with DMAP to afford the desired 8-membered ring lactone in 84% yield at room temperature, and the corresponding diolide was not produced.Thus, an efficient method for the preparation of the synthetic precursor of octalactins was established via the effective, construction of the medium-sized ring lactone moiety.