Synthetic Studies of Fungal Metabolites: Ascofuranone and Colletochlorin D

Article abstract of DOI:10.1021/jo00133a027

Procedures have been developed for the synthesis of hexasubstituted aromatic rings which are present in many fungal metabolites such as ascofuranone and colletochlorin D. (3-Bromo-5-chloro-2,6-dimethoxy-p-tolyl)acetaldehyde was synthesized from orcinol in eight steps.This aldehyde was converted to 2-bromo-6-chloro-3,5-dimethoxy-4-(3-methyl-2-butenyl)toluene which was subsequently formylated to afford 3-chloro-4,6-dimetoxy-2-methyl-5-(3-methyl-2-butenyl)benzaldehyde.Although various demethylation procedures were tried, demethylation of both methoxy groups could not be accomplished.In our attempts to synthesize ascofuranone, (3-bromo-5-chloro-2,6-dimethoxy-p-tolyl)acetaldehyde was treated with isopropenylmagesium bromide to afford an unsteble allylic alcohol which was immediately subjected to the conditions of the "orthoacetate Claisen rearrangement" to give 2-bromo-6-chloro-4<(E)-5-(ethoxycarbonyl)-3-methyl-2-pentenyl>-3,5-dimethoxytoluene.This compound was then converted to 2-bromo-6-chloro-3,5-dimethoxy-4-<(E)-3-methyl-2-hexenyl-6-(triphenylphosphonio)hex-2-enyl>toluene bromide in three steps.All attempts to carry out a Wittig reaction between this compound and 6,6-dimethyl-1,4,7-trioxaspiro<4.4>non-8-yl methyl ketone failed.Other coupling methods were equally unsuccesful.