Isocoumarins

The work presented here consists of general introduction, nomenclature, structural type, biosynthesis, extensive examples on biological activities, some of the most important methods of synthesis and reactions of isocoumarins and 3,4-dihydroisocoumarins from the literature. It includes a partial synthesis of naturally occurring thunberginol C, isolated from Hydrangea macrophylla var. thunbergii., which was conveniently synthesized in a quantitative yield with key intermediate 3,5-dimethoxyhomophthalic acid (which itself is synthesized through several steps) by direct condensation with p-methoxybenzoyl chloride to yield 3-(4’-methoxyphenyl)-6,8-dimethoxyisocoumarin related to thunberginol C. It also includes synthesis of 3,4,5-trimethoxyhomophthalic acid involving four steps which is an important intermediate towards the synthesis of naturally occurring isocoumarins and dihydroisocoumarins. It includes the synthesis of some non-naturally occurring 3-(2’’/3’’/4’’-chlorobenzyl)isocoumarins. The conversion of 3-(2’’-Chlorobenzyl)isocoumarin to keto-acid, then to respective racemic hydroxy-acid and finally to (dl)-3-(2’’-chlorobenzyl)-3,4-dihydroisocoumarin is also reported.