Isocoumarin and Its Derivatives: An Overview on their Synthesis and Applications

Abstract

The prevalence of isocoumarins in numerous natural products that exhibit a wide range of biological activities has generated a continued and enormous interest among synthetic and medicinal chemists. The isocoumarin framework represents one of the privileged structures for the development of natural product-inspired compounds of potential biological interest. Considerable efforts have been devoted towards the synthesis of isocoumarins via either traditional or transition-metal catalyzed reactions. Among the metal catalyzed reactions, the use of Cu, Pd, Ag, Ru, Rh or Ir salts/complexes for the construction of isocoumarin ring are noteworthy. Among the other methodologies, halo-lactonization emerged as a practical process. Apart from preparing a variety of isocoumarins and thienopyranones, synthesis of naturally occurring and bioactive isocoumarins have been carried out by using cutting edge technologies. This review article will briefly cover all these aspects along with the synthetic utility of isocoumarins, highlighting recent developments.

Plant Bioactive Metabolites and Drugs Produced by Endophytic Fungi of Spermatophyta

“…These compounds are widespread in edible plants, therefore commonly assumed through dietary exposure, and considered interesting prospects for a pharmaceutical exploitation due to their antioxidant, anti-inflammatory, anticoagulant, antimicrobial, anticancer, antihypertensive, antihyperglycemic, and neuroprotective properties [116,117]. A number of these compounds primarily known from plants have recently started being reported as metabolites of endophytic fungi, such as coumarin found in extracts of strains of Alternaria spp., Penicillium spp.…”

Synthetic Methods of Isocoumarins and Phosphaisocoumarins through CH Activation

“…They exhibit a wide range of bioactivity, including antiinflamatory, antifungal, antibacterial, antiulcer, herbicidal, antiangiogenic, and cytotoxic effects (Scheme ). In particular, isocoumarins serve as essential intermediates in the synthesis of a multitude of other compounds such as isoquinolines, isocarbostyrils, and isochromenes . In numerous cases, isocoumarins are prepared from the transition metal‐catalyzed intramolecular cyclization of substrates bearing an alkyne as well as a carboxylic acid group generated from the Sonogashira reaction of ortho ‐halo‐ or trifluoromethylsulfonyloxy aromatic acids with terminal alkynes.…”

N‐Heterocyclic Carbene Catalysis as a Tool for Gaining Access to the 3,4‐Dihydropyran‐2‐one Skeleton

“…The 3,4‐dihydropyran‐2‐one system constitutes the key functionalized subunit of isocoumarins, a family of natural occurring compounds that show a broad spectrum of pharmacological activities such as antifungal, anti‐inflammatory, antimicrobial, phytotoxic and cytotoxic, to mention only a few. For example, the isocoumarin NM‐3,1 an analogue of the natural product cytogenin, inhibits the growth of human hendotelial cells in culture and tumour angiogenesis in human tumour xenograft models 2. The isocoumarin fragment is also a component in rubromycins, a class of antitumour antibiotics attracting intensive synthetic efforts 3.…”