Progress in the Development of Pyrophosphate Bioisosteres: Synthesis and Biomedical Potential of 1-Fluoro- and 1,1-Difluoromethylene-1,1-bisphosphonates

Title:Progress in the Development of Pyrophosphate Bioisosteres: Synthesis and Biomedical Potential of 1-Fluoro- and 1,1-Difluoromethylene-1,1-bisphosphonates

Volume: 18 Issue: 11

Author(s): Vadim D. Romanenko and Valery P. Kukhar

Affiliation:

Keywords: Enzyme inhibitors, fluorinated bisphosphonates, modified nucleoside polyphosphates, phosphate mimics, synthetic methods

Abstract: Mono- and difluoromethylenebisphosphonates are of great synthetic and biological interest since they are among the best isopolar pyrophosphate mimics. This review will emphasize preparation and some of the most important applications of these compounds. The following synthetic approaches to fluoromethylenebisphosphonates are summarized: (i) electrophilic halogenation, (ii) Arbuzov and Michaelis-Becker reactions, (iii) direct electrophilic phosphorylation of fluoromethylphosphonate carbanions, and (iv) autocondensation of fluoromethylphosphonate carbanions. Emphasis is given to the synthesis and biomedical application of modified nucleoside polyphosphates, incorporating fluoromethylenebisphosphonate scaffold.

Cite this article as:

Romanenko D. Vadim and Kukhar P. Valery, Progress in the Development of Pyrophosphate Bioisosteres: Synthesis and Biomedical Potential of 1-Fluoro- and 1,1-Difluoromethylene-1,1-bisphosphonates, Current Organic Chemistry 2014; 18 (11) . https://dx.doi.org/10.2174/138527281811140815124708