Naturally occurring mellein-type 3,4-dihydroisocoumarins and related lactones: synthetic approaches - a review

Mellein and its derivatives are the most common 3,4-dihydroisocoumarins and are known to exhibit an array of biological activities such as antibacterial, antifungal, antimalarial, antiallergic, antitumor, anti-inflammatory, antiulcer, pheromonal, plant growth-promoting and antileukemic activities. Other mellein derivatives are recognized phytotoxins, neurotoxins, hepatotoxins, nephrotoxins and teratogens.Consequently, considerable efforts have been directed at studying these natural products. While most of the reported studies have focused on the isolation, characterization and bioassay studies of melleins, a number of synthetic studies have also been reported. This paper focuses on synthetic approaches towards these biologically active and, thus, potentially useful natural products. The aim is to bring together some of the earliest (past) and the more recent (present) and, concurrently, propose prospective (projected) synthetic methodologies. Therefore, this paper provides an overview of the existing and some potential synthetic routes toward melleins and, thus, provides a researcher with ideas and opportunities to choose and apply one or a blend of these synthetic strategies depending on accessible research facilities.  Moreover, the projected synthetic strategies focus on the utilization of anacardic acid from Cashew Nut Shell Liquid (CNSL) - a readily available natural resource. Utilization of CNSL, which is considered a waste product, adds value to the cashew crop. Keywords : Melleins, 3,4-dihydroisocoumarins, synthetic methodologies, natural products, CNSL, 3,4-DHICs, lactones