A General Synthetic Approach to Hydroquinone Meroterpenoids: Stereoselective Synthesis of (+)-(S)-Metachromin V and Alliodorol

Abstract

A new general synthetic approach to hydroquinone meroterpenoids is here described. The framework of the aforementioned natural compounds was built up through the Li2CuCl4 catalysed cross coupling reaction of the 4-substituted-( E)-prenyl acetates 9 with 2,5-bis(benzyloxy)phenyl magnesium bromide 8 as a key step. The latter sp3-sp2 coupling affords the products in good chemical yields and in very high stereoisomeric purity. A further key step of the present synthetic method consists of the removal of the benzylic protecting groups by a very mild procedure based on the use of lithium naphthalenide. The latter reagent, in combination with aliphatic dialkylamines, is able to cleave all the benzylic protecting groups leaving unaffected the polyenic moieties. By these means, we devised a new synthesis of the natural hydroquinone geranylhydroquinone, farnesylhydroquinone, metachromin V and alliodorol. In addition, the marine meroterpenoid, (+)-( S)-metachromin V, was synthesized for the first time; its chemical structure was confirmed and its absolute configuration was unambiguously assigned.