A versatile total synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition.
A new versatile synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition was carried out. The coupling reaction between benzonitrile 6 with o-toluamides (8a-c) afforded 3-arylisoquinolines (9a-c) that were transformed to the protoberberines (11a-c) or benzo[c]phenanthridines (14a-c). These compounds were synthesized by ring closure of the two-carbon chain on either position 2 or 4 of the 3-arylisoquinolinone (9a-c). Several kinds of substituted benzo[c]phenanthridine alkaloids such as oxysanguinarine, oxyavicine, and oxynitidine as well as protoberberines such as 8-oxocoptisine, 8-oxopseudoberberine, and 8-oxopseudocoptisine were synthesized.
Le
Thanh Nguyen
TN
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Yong-Bong dong, Buk-gu, Kwangju 500-757 Korea.
Gang
Seong Gyoung
SG
Cho
Won-Jea
WJ
D000470:Alkaloids / Q000138:chemical synthesis*; D001600:Berberine Alkaloids / Q000138:chemical synthesis*; D003500:Cyclization; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis; D010617:Phenanthridines / Q000138:chemical synthesis*; D014050:Toluene / Q000737:chemistry
D000470:Alkaloids; D001600:Berberine Alkaloids; D009570:Nitriles; D010617:Phenanthridines; C009090:protoberberine; D014050:Toluene; D008094:Lithium