Phosphonate Biochemistry

Abstract

Organophosphonic acids are unique as natural products in terms of stability and mimicry. The C-P bond that defines these compounds resists hydrolytic cleavage, while the phosphonyl group is a versatile mimic of transition-states, intermediates, and primary metabolites. This versatility may explain why a variety of organisms have extensively explored the use organophosphonic acids as bioactive secondary metabolites. Several of these compounds, such as fosfomycin and bialaphos, figure prominently in human health and agriculture. The enzyme reactions that create these molecules are an interesting mix of chemistry that has been adopted from primary metabolism as well as those with no chemical precedent. Additionally, the phosphonate moiety represents a source of inorganic phosphate to microorganisms that live in environments that lack this nutrient; thus, unusual enzyme reactions have also evolved to cleave the C-P bond. This review is a comprehensive summary of the occurrence and function of organophosphonic acids natural products along with the mechanisms of the enzymes that synthesize and catabolize these molecules.

Selective P−C(sp3) Bond Cleavage and Radical Alkynylation of α‐Phosphorus Alcohols by Photoredox Catalysis

“…Phosphorus radicals are versatile reactive intermediates for organophosphorus syntheses, in which the phosphorus–hydrogen, phosphorus–heteroatom and phosphorus–carbonyl compounds are used as P‐radical precursors – . α ‐Phosphorus alcohols are important structural motifs in organic synthesis, which can be prepared easily by the Pudovik reaction and represent an attractive phosphorus radical precursor . The alkoxyl radical is known for C−C bond cleavage reactions, however the counterpart P−C bond cleavage from α ‐phosphorus alcohols is unknown and further functionalization is elusive (Scheme b) .…”

Inverting External Asymmetric Induction via Selective Energy Transfer Catalysis: A Strategy to β‐Chiral Phosphonate Antipodes

“…Given the value of alkenes as pro‐chiral substrates in asymmetric catalysis, and the renaissance of positional and geometric isomerisation enabled by selective energy transfer, an isomerisation/stereospecific reduction sequence would provide a useful platform to validate the working hypothesis. To that end, α,β‐unsaturated phosphonates were explored due to their prominence in the pharmaceutical and agrochemical sectors, biochemical significance and venerable history in synthesis (Scheme ) . Herein, the first photocatalytic E → Z isomerisation of α,β‐unsaturated phosphonates is disclosed using an inexpensive organocatalyst.…”

Inversion externer asymmetrischer Induktion durch selektive Energietransfer‐Katalyse: Strategie zu β‐chiralen Phosphonat‐Antipoden

“…Basierend auf der derzeitigen Prominenz positioneller und geometrischer Isomerisierungen durch selektiven Energietransfer und der Prochiralität von Alkenen, bietet eine Sequenz aus Isomerisierung und stereospezifischer Reduktion eine sinnvolle Plattform zur Validierung dieser Arbeitshypothese. Aufgrund ihres außerordentlichen Nutzen für den pharmazeutischen und agrochemischen Sektor, sowie ihrer biochemischen Bedeutsamkeit und imposanten Geschichte in organischer Synthese wurden α,β‐ungesättigte Phosphonate als mögliche Substrate ausgewählt (Schema ) . In dieser Arbeit wird die erste photokatalytische E → Z Isomerisierung von Vinylphosphonaten unter Verwendung eines preisgünstigen Organokatalysators beschrieben.…”