Shirai Atsushi, Miyata Okiko, Tohnai Norimitsu, Miyata Mikiji, Procter David J, Sucunza David, Naito Takeaki
Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Japan.
J Org Chem. 2008 Jun 20;73(12):4464-75. doi: 10.1021/jo800560p. Epub 2008 May 13.
The asymmetric total synthesis of martinellic acid, the first pyrrolo[3,2-c]quinoline alkaloid found in nature, is described. Three key steps in our synthesis of (-)-martinellic acid are the Bu(3)SnH-promoted radical addition-cyclization-elimination (RACE) reaction of an oxime ether with an alpha,beta-unsaturated ester to generate the pyrrolo[3,2-c]quinoline core, a chemoselective lactam carbonyl reduction, and guanidinylation under Mitsunobu reaction conditions. The key radical cyclization has also been investigated by using SmI(2). (-)-Martinellic acid was synthesized from commercially available methyl 4-bromo-3-methylbenzoate in fewer steps than previous syntheses and in an improved overall yield.
本文描述了自然界中发现的首个吡咯并[3,2 - c]喹啉生物碱马替奈林酸的不对称全合成。我们合成（ - ） - 马替奈林酸的三个关键步骤是：肟醚与α,β - 不饱和酯在Bu(3)SnH促进下发生自由基加成 - 环化 - 消除（RACE）反应以生成吡咯并[3,2 - c]喹啉核心；化学选择性内酰胺羰基还原；以及在光延反应条件下进行胍基化反应。还利用SmI(2)对关键的自由基环化反应进行了研究。（ - ） - 马替奈林酸由市售的4 - 溴 - 3 - 甲基苯甲酸甲酯合成，与以往合成方法相比，步骤更少，总产率更高。
