BISPHOSPHONATE PRODRUGS. SYNTHESIS AND IDENTIFICATION OF (1-HYDROXYETHYLIDENE)-1,1-BISPHOSPHONIC ACID TETRAESTERS BY MASS SPECTROMETRY, NMR SPECTROSCOPY AND X-RAY CRYSTALLOGRAPHY

Abstract

The preparation and identification of symmetric, H₃CC(OH)[P(O)(OR)₂]₂, where R˭Me, Et, Prⁱ, Ph, and non-symmetric, H₃CC(OH)[P(O)(OR)¹)(OR²)][P(O)(OR³)(OR⁴)], where R¹˭Me, R²˭R³˭R⁴˭Ph; R¹˭R²˭R³˭Ph, R⁴˭Me; R¹˭R³˭Me, R²˭R⁴˭Ph; R¹˭R²˭Et, Prⁱ, Ph and R³˭R⁴˭Me; Tetraester derivatives of etidronate have been studied. Compounds were prepared from HP(O)(OR¹)(OR²) and AcP(O)(OR³)(OR⁴) species under reflux. Mechanism studies have been made using HP(O)(OCD₃)(OPh) and AcP(O)(OMe)(OPh) as starting materials. ¹H, ¹³C, ³¹P NMR data and the MS fragmentation data in the gas phase are reported. The solid-state structures are given for three of the compounds, where R˭Et, Ph and R¹˭R²˭Ph, R³˭R⁴˭Me.

Key Words:

• etidronate
• esters
• NMR
• MS
• X-ray