Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate

The biosynthesis of steroids and triterpenoids

“…254 A novel radiometric assay for SQS activity, intended for development of new inhibitors, has been described 255 and an improved method for analysis and purification of the FPP substrate has been reported. 256 The most important new SQS inhibitors to be discovered are the bisphosphonates (18 and other isomeric long chain alkyl phosphates), [257][258][259][260][261][262][263] which are thought to mimic the FPP substrate, and the zaragozic acids 264 (ZGAs, squalestatins [265][266][267][268] ), polyketide 269,270 fungal metabolites which are active at nano-to pico-molar concentrations 271,272 and may mimic the reaction intermediate PSPP. ZGAs A (squalestatin 1; 19), 273,274 B (20), C (21) 275 and D ( 22) 276 share a polar 2,8-dioxabicyclo[3.2.1]octane-4,6,7-trihydroxy-3,4,5tricarboxylic acid core and vary in the composition of the lipophillic 6-O-acyl and 1-alkyl side-chains.…”

A novel bisphosphonate inhibitor of squalene synthase combined with a statin or a nitrogenous bisphosphonate in vitro

“…Standard conversion of the free hydroxyl group to the allylic bromide was performed using PBr 3 . After workup, the bromides were used without further purifi cation in the subsequent alkylation of tetraethyl methylenebisphosphonate ( 29 ). The resulting phosphonate esters 17, 18, and 19 were hydrolyzed to their corresponding salts (3, 4, and 5, respectively) under standard McKenna procedures ( 30 ).…”

Synthesis of New Polyphosphonic Acids

“…They are of considerable biological, industrial, and chemical importance. 1,2 Thus, the diphosphonates are widely used as analogues of pyrophosphates and nucleotides since the P C P bond shows a greater inertness to enzymatic hydrolysis than the P O P linkage. 3 Phosphonates play an important role as chelating agents of divalent metals.…”