Total Synthesis of (−)-Martinellic Acid via Radical Addition−Cyclization−Elimination Reaction

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 Bu3SnH-promoted radical addition−cyclization−elimination (RACE) reaction of an oxime ether with an α,β-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 SmI2. (−)-Martinellic acid was synthesized from commercially available methyl 4-bromo-3-methylbenzoate in fewer steps than previous syntheses and in an improved overall yield.