A multicomponent carba-Betti strategy to alkylidene heterodimers-total synthesis and structure-activity relationships of arzanol

Abstract

Using the synthesis of the heterodimeric phloroglucinyl pyrone arzanol as a benchmark reaction, a carba-version of the Betti multicomponent reaction has been developed. Capitalizing on the fluorous activation of the phenolic component and the use of iminium ions as bivalent and "transmissive" aldehyde equivalents, the reaction has been used to colonize a biologically privileged but previously inaccessible area of chemical space and investigate the structure-activity relationships of arzanol towards a series of proinflammatory targets (mPGES-1, 5-LO). Using the synthesis of the heterodimeric phloroglucinyl pyrone arzanol as a benchmark reaction, a carba-version of the venerable Betti multicomponent reaction has been developed and applied to the "colonization" of a biologically privileged but previously inaccessible area of chemical space. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.