Recent advances in synthetic approaches for biologically active organic dithiocarbamates

Abstract

The chemically and medicinally versatile dithiocarbamates play a significant role in advancing various fields, including agriculture, chemical synthesis, and environmental remediation. However, dithiocarbamates have primarily been utilised as pesticides and fungicides for crop protection since the 1930s. Recently, the revival of dithiocarbamates from agrochemicals to repurposed drugs for treating life-threatening diseases like cancer and microbial infections has stimulated medicinal chemists to reinvestigate their unmet potential. Furthermore, dithiocarbamates containing diversified organic functionalities have shown promising antifungal activity against fungal-resistant phytopathogens, offering a solution to addressing the global threat of fungal resistance. Consequently, the synthesis of multifaceted S and N-functionalized organic dithiocarbamates using diverse organic substrates has resurfaced in synthetic and medicinal chemistry research. There is also a growing trend to develop more convenient synthetic approaches for synthesising organic dithiocarbamates featuring various green chemistry aspects, including alternative or renewable energy resources, green solvents, solvent-free reaction conditions, and cost-effectiveness. These greener approaches are also associated with high efficiency, better selectivity, broad substrate scope, outstanding yields, operational simplicity, and viability. This review provides an in-depth overview of the recent developments in the diverse synthetic routes for preparing novel organic dithiocarbamates, including multi-component approaches involving the reaction of amines, carbon disulfide, and a wide range of organic substrates. The emerging methodologies for directly synthesising S-alkyl and S-aryl dithiocarbamates using commercially available and non-hazardous tetraalkylthiuram disulfides or monosulfides as organic precursors are also comprehensively discussed in this article. This review also highlights recently developed unconventional greener protocols using alternative reactants instead of carbon disulfide or thiuram disulfides.