Synthesis and Biological Applications of Phosphinates and Derivatives

Abstract

This review first outlines general considerations on phosphinic acids and derivatives as bioisosteric groups. The next sections present key aspects of phosphinic acid-based molecules and include a brief description of the biological pathways involved for their activities. The synthetic aspects and the biological activities of such compounds reported in the literature between 2008 and 2013 are also described.

Diethyl boronobenzylphosphonates as substrates in Petasis reaction

“…Frequently such efforts appeared successful and resulted in compounds of variable and promising physiological activity and in commercially available substances. [1][2][3][4][5] In addition, aminophosphonic acids and their derivatives are able to form complexes with a variety of metal ions. 6 These findings ensure that they still continue to attract wide interest.…”

A General Protocol for the Synthesis of H-α-Hydroxyphosphinates

“…Phosphinates represent consequently interesting scaffolds for the development of novel therapeutic molecules. 1 More particularly, H-phosphinates (R 1 = H, R 2 = carbon chain) can be precursors of phosphinates (R 1 /R 2 = carbon chain) as phosphinic acid pseudopeptides. These peptide isosteres contain a non-hydrolyzable phosphinic acid function instead of a peptide bond that can mimic the substrate transition state for hydrolytic enzymes 2 as matrix metalloproteinases (MMPs) 3 and aspartic acid proteinases.…”

“…Furthermore, our methodology furnishes easily purified compounds in very satisfying yields and shorter times than previously reported in the literature. 8 At the outset of this study, the equimolar Abramov reaction was conducted with hypophosphorous acid (1) and benzaldehyde (3a) in the presence of N,O-bis(trimethylsilyl)acetamide (BSA) in dichloromethane at 0 °C (Table 1). Initially, BSA (3 equiv) was dropwise mixed with hypophosphorous acid (1) over 40 minutes to generate in situ the bis(trimethylsilyl)phosphonite (2), which was subsequently added over 20 minutes to a solution of benzaldehyde (1 equiv) in dichloromethane at 0 °C ( Table 1, entries 1-3: method A).…”

“…8 At the outset of this study, the equimolar Abramov reaction was conducted with hypophosphorous acid (1) and benzaldehyde (3a) in the presence of N,O-bis(trimethylsilyl)acetamide (BSA) in dichloromethane at 0 °C (Table 1). Initially, BSA (3 equiv) was dropwise mixed with hypophosphorous acid (1) over 40 minutes to generate in situ the bis(trimethylsilyl)phosphonite (2), which was subsequently added over 20 minutes to a solution of benzaldehyde (1 equiv) in dichloromethane at 0 °C ( Table 1, entries 1-3: method A). A 31 P NMR spectrum after 1 hour indicated a total conversion and the expected α-hydroxyphosphinate 4a was easily isolated as a solid sodium salt in a good yield of 70% (entry 1).…”

“…This reaction indeed could proceed because of the P(V)/P(III) species equilibrium existing between hypophophorous acid (1) and its phosphonite form. The silylation actually allows the equilibrium displacement by trapping the phosphonite.…”