Scalable synthesis of cladosporin.

Graphical abstract Highlights • Developed a scalable synthetic route to cladosporin, a potent antimalarial natural product. • Mitsunobu inversion and carbon monoxide insertion are the key steps of the present synthesis. • The target natural product cladosporin has been synthesized in gram scale for the first time. Abstract Cladosporin, a secondary metabolite isolated from fungal sources like Cladosporium cladosporioides and Aspergillus flavus was found to exhibit selective nano-molar activity against malarial parasite Plasmodium falciparum by inhibiting parasitic protein biosynthesis. In addition, this natural product has a broad range of bioactivities including, antiparasitic, antifungal, antibacterial as well as plant growth inhibition. However, it has limited availability from the natural sources for further development. Herein, we report a modified and improved synthetic route which led us to produce this potent natural product in a gram scale. Conversion of the undesired diastereomer to desired one via Mitsunobu inversion of secondary alcohol and carbon monoxide insertion reaction towards the construction of isocoumarin unit are the key features of the present synthesis. [ABSTRACT FROM AUTHOR]