Synthesis of Triple-Bond-Containing 1?Hydroxy-1,1-bisphosphonic Acid Derivatives To Be Used as Precursors in 'Click' Chemistry: Two Examples

摘要

The synthesis of novel (ω-alkynyl-1-hydroxy-1,1- diyl)bisphosphonic acid tetramethyl esters (1a?c), their P,P′- dimethyl esters (2a?c), and two trimethyl ester derivatives (3a and 3b) is reported. The prepared compounds can be attached to many kinds of molecules containing azide (?N_3) functionalities using a "click" chemistry approach. As an example, bisphosphonate trimethyl ester 3a and P,P′-dimethyl ester 2b were attached to triethylene glycol to form triethylene glycol?bisphosphonate conjugates 4 and 5 as model compounds for further studies in, for example, nanoparticle targeting.