Yamada Ken-ichi, Sato Tomohiro, Hosoi Masaki, Yamamoto Yasutomo, Tomioka Kiyoshi
Kyoto University, Japan.
Chem Pharm Bull (Tokyo). 2010 Nov;58(11):1511-6. doi: 10.1248/cpb.58.1511.
Stereoselective formal synthesis of (+)-allokainic acid was accomplished starting from L-glutamate by using a thiol-mediated acyl radical cyclization as a key step. The cyclization of a formylalkenoate proceeded in a highly diastereoselective manner to give trans-4,5-disubstituted pyrrolidin-3-one without the production of the cis-isomer. The pyrrolidinone was then converted into the established synthetic intermediate of (+)-allokainic acid via the iron-catalyzed coupling reaction with an isopropenyl Grignard reagent.
以L-谷氨酸为起始原料，通过硫醇介导的酰基自由基环化反应作为关键步骤，完成了(+)-别藻氨酸的立体选择性形式合成。甲酰基链烯酸酯的环化反应以高度非对映选择性的方式进行，得到反式-4,5-二取代吡咯烷-3-酮，而不产生顺式异构体。然后，通过与异丙烯基格氏试剂的铁催化偶联反应，将吡咯烷酮转化为(+)-别藻氨酸已有的合成中间体。
