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A Concise Total Synthesis of the Azaphenanthrene Alkaloid Eupolauramine

2001; American Chemical Society; Volume: 66; Issue: 24 Linguagem: Inglês

10.1021/jo0105944

1520-6904

Christophe Hoarau, Axel Couture, Hélène Cornet, Éric Deniau, Pierre Grandclaudon,

Advanced Synthetic Organic Chemistry

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 E1CB 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.