Semisynthesis of a mellein-type 3,4-dihydroisocoumarin from cashew nut shell liquid (CNSL)

Abstract

Mellein-type 3,4-dihydroisocoumarin  39  (i.e., 8-methoxy-3-tridecyl-3,4-dihydroisocoumarin or 8-methoxy-3-tridecylisochroman-1-one), and its precursors, namely, methyl 2-methoxy-6-pentadecylbenzoate (37), methyl 2-methoxy-6-pentadecanoylbenzoate (38) and (E)-methyl 2-methoxy-6-(pentadec-1-enyl)benzoate (19) were synthesized from anacardic acid (12) as a starting material obtained from Cashew Nut Shell Liquid (CNSL) in an overall yield of 78%. The transformation of  12  to  39  involved protection of the reactive phenolic and carboxylic acid groups of compound  12  through methylation followed by hydrogenation so as to saturate the mono-, di- and tri-unsaturated C₁₅  chains of anacardic acid (12). Subsequent benzylic oxidation and reduction of the keto functional group with concomitant dehydration of the alcohol led to the formation of  19,which after deprotection of  the carboxyl group followed by lactonization, gave the mellein-type 3,4-dihydroisocoumarin  39.

Keywords:         Semisynthesis, 3,4-dihydroisoumarin, Anacardic acid, Cashew Nut Shell Liquid (CNSL)