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 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.
Shirai
Atsushi
A
Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe, Japan.
Miyata
Okiko
O
Tohnai
Norimitsu
N
Miyata
Mikiji
M
Procter
David J
DJ
Sucunza
David
D
Naito
Takeaki
T
D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared
D011758:Pyrroles; D011804:Quinolines; C432345:martinellic acid