Chemistry of difluoromethylene phosphonates: history, state of the art, and prospects

Abstract

Difluoromethylene phosphonates are non-hydrolyzable bioisosteres of phosphates. They have proven their efficiency as inhibitors of the enzymes that specialize in utilizing these essential biogenic molecules. Difluoromethylene phosphonates show a broad spectrum of biological activity and are used as molecular tools to study enzymes and enzyme-substrate interactions. In this review, we briefly summarize the importance of difluoromethylene phosphonates as a distinct class of synthetic phosphonates resulting from multidisciplinary efforts of the organophosphorus, organofluorine, and bioorganic research communities. We outline the development of the synthetic chemistry of difluoromethylene phosphonates from the historical perspective, discuss the most recent trends in the field, and highlight the existing challenges and unsolved questions