A concise total synthesis of the azaphenanthrene alkaloid eupolauramine.
A six-step total synthesis of the azaphenanthrene alkaloid eupolauramine 1 has been achieved using combinational metalation-cyclization tactics. The synthetic route involved first the construction of the azaisoindolinone 9 by aryne-mediated cyclization of he phosphorylated pyridocarboxamide 7 and subsequent dephosphorylation. Metalation of 9 followed by connection of the hydroxybenzyl appendage and E(1)CB anti-elimination allowed the formation of the halogenoarylmethylene azaisoindolinone 4 in the exclusive E-form. Oxidative radical cyclization gave rise to the azaphenanthrene skeleton and regioselective bromination of 3 induced the incorporation of the bromine atom at the 6-position of the azaphenanthrene lactam. Ultimate replacement of the bromine atom of 2 by the methoxy functionality by sequential transmetalation, in situ oxidation, and O-methylation of the phenolic derivative 14 completed the synthesis of the target natural product eupolauramine.
Hoarau
C
C
Laboratoire de Chimie Organique Physique, UPRES A-CNRS 8009, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq Cedex, France.
Couture
A
A
Cornet
H
H
Deniau
E
E
Grandclaudon
P
P
D000470:Alkaloids / Q000138:chemical synthesis*; D001372:Aza Compounds / Q000138:chemical synthesis*; D010616:Phenanthrenes / Q000138:chemical synthesis*; D014197:Trees / Q000737:chemistry
D000470:Alkaloids; D001372:Aza Compounds; D010616:Phenanthrenes; C447626:eupolauramine