The Preparation of New Phosphorus-Centered Functional Groups for Modified Oligonucleotides and Other Natural Phosphates

Abstract

Efforts to develop synthetic methodologies allowing the preparation of α,α–difluorophosphonothioates, α,α–difluorophosphonodithioates, α,α–difluorophosphono-trithioates, and α,α–difluorophosphinates are reviewed in the light of applications in the field of modified oligonucleotides and cyclitol phosphates. Two successful approaches have been developed, based either on the addition of phosphorus-centered radicals onto gem–difluoroalkenes or on a process involving the addition of lithiodifluorophosphono-thioates 91 onto a ketone and the subsequent deoxygenation reaction of the adduct. The radical route successfully developed a practical route to α,α–difluoro–H–phosphinates which proved to be useful intermediates to a variety of phosphate isosters. The ionic route led to the first preparation of phosphonodifluoromethyl analogues of nucleoside–3’–phosphates.

Phosphorus‐Bearing Lithium Compounds in Modern Synthesis

“…These anions can be prepared by proton removal with lithium diisopropylamide (LDA) and reductive lithium insertion into a C-Br and C-S bond of the corresponding precursor. Piettre et al [14] synthesized a series of phosphonodifluoromethyl analogs of nucleoside-3 ′ -phosphates 31 via a multistep process where the difluoromethylphosphonothioate group was introduced onto a suitably protected ketosugar 29 through addition of C α -lithiated α,α-difluoromethylphosphonothioate to give the adduct 30.…”

Characterization of Phosphate Solubilizing Bacteria in Sediments from a Shallow Eutrophic Lake and a Wetland: Isolation, Molecular Identification and Phosphorus Release Ability Determination

“…Indeed, bacteria can dissolve insoluble inorganic P (IP) with the action of low molecular weight organic acids which are produced in the periplasmic space of some Gram-negative bacteria through a direct glucose oxidation pathway [ 14 ]. Digenesis of organic matter is mainly dependent on bacterial activity since the mineralization of these compounds is carried out by means of several phosphatases which are secreted by microorganisms [ 15 ]. These groups of bacteria that can directly influence P release have been termed ‘phosphate solubilizing bacteria’.…”

Recent advances in sulfur- and phosphorous-centered radical reactions for the formation of S–C and P–C bonds

“…These compounds can be easily converted to difluorophosphonates, difluorophosphonothioates, and difluorophosphinates. They are valuable intermediates for the synthesis of bioactive isosteres of natural phosphates 262. Under appropriate conditions, phosphinates can be used as a precursor for double radical addition.…”