o-Nitrophenyltriflates in Quinoline Synthesis: Easy Access to a Streptonigrin Synthon

Abstract

An efficient route to a wide range of 2-hydroxyquinolines from onitrophenyltriflates via a Heck reaction is reported, with emphasis on the preparation of a synthetic equivalent of the streptonigrin AB ring system.Streptonigrin (1) is a highly functionalised tetracyclic compound which shows potent anticancer activity.'Whereas previous total syntheses2 involved complex ring forming reactions and functional group manipulations, our overall strategy is more convergent and based on the use of preformed rings.As past of our investigation, preparation of the AB quinoline-quinone structure came under attention.Our strategy involves the Heck reaction' of an appropriately-substituted benzene with methyl acrylate, followed by cyclisation, to afford a substituted 2-hydroxyquinoline which can be converted into the reactive 5.8-dione in the latter stages of the synthesis.Conversion of the 2-hydroxyquinoline into the 2-chloro or 2-triflyl derivative would provide a suitable substrate for palladium catalysed cross coupling to the CD moiety.