Fujioka Hiromichi, Sawama Yoshinari, Kotoku Naoyuki, Ohnaka Takuya, Okitsu Takashi, Murata Nobutaka, Kubo Ozora, Li Ruichuan, Kita Yasuyuki
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan.
Chemistry. 2007;13(36):10225-38. doi: 10.1002/chem.200700871.
The concise asymmetric total synthesis of scyphostatin has been achieved by condensation of the optically active cyclohexane unit, prepared from the commercially available 1,4-cyclohexadiene by our own method, and the side chain, prepared by the method developed by Hoye and Tennakoon (T. R. Hoye, M. A. Tennakoon, Org. Lett. 2000, 2, 1481-1483). The modification of the epoxy cyclohexenone unit was achieved in a late stage of the total synthesis, and deprotection of the primary alcohol was conducted in the final step. During the synthesis several key reactions were attained: 1) intramolecular bromoetherification of the cyclohexadiene acetal; 2) stereoselective introduction of the tertiary alcohol, 3) deprotection of the acetal function to the aldehyde by combination with silyl triflate/2,4,6-collidine and the one-pot synthesis of the disilyl aldehyde compounds, with different types of silyl groups, from the dihydroxy acetal compounds; and 4) facile deprotection of the 2,4-dimethoxyphenylmethyl ((2,4)DMPM) protecting group of the primary alcohol.
通过将由市售1,4 - 环己二烯经我们自己的方法制备的光学活性环己烷单元与由霍耶（T. R. Hoye）和坦纳昆（M. A. Tennakoon）开发的方法（《有机快报》，2000年，第2卷，第1481 - 1483页）制备的侧链进行缩合，实现了海蜇抑素的简洁不对称全合成。环氧环己烯酮单元的修饰在全合成的后期阶段完成，伯醇的脱保护在最后一步进行。在合成过程中实现了几个关键反应：1）环己二烯缩醛的分子内溴醚化；2）叔醇的立体选择性引入；3）通过三氟甲磺酸硅酯/2,4,6 - 可力丁组合将缩醛官能团脱保护为醛，并从二羟基缩醛化合物一锅法合成具有不同类型硅烷基团的二硅烷基醛化合物；以及4）伯醇的2,4 - 二甲氧基苯基甲基（(2,4)DMPM）保护基团的简便脱保护。
