Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Angew Chem Int Ed Engl. 2017 Mar 6;56(11):2955-2959. doi: 10.1002/anie.201611878. Epub 2017 Feb 7.
A new class of phosphanylmethylphosphonate reagents has been developed to enable the controlled synthesis of methylene bisphosphonate mono- and diesters. Condensation of such reagents with an alcohol of choice through azole-mediated phosphoramidite chemistry followed by in situ oxidation provides orthogonally protected methylene bisphosphonate tetraesters. Global deprotection of the tetraester leads to terminal methylene bisphosphonates. Alternatively, selective deprotection at the terminal phosphonate followed by a condensation between the acquired methylene bisphosphonate triester and a second alcohol leads to methylene bisphosphonates diesters.
一类新型膦甲基膦酸酯试剂已被开发出来，用于控制亚甲基双膦酸单酯和双酯的合成。通过唑介导的磷酰胺化学与所选醇进行缩合，然后进行原位氧化，提供了正交保护的亚甲基双膦酸四酯。四酯的全脱保护得到末端亚甲基双膦酸。或者，在末端膦酸酯选择性脱保护后，获得的亚甲基双膦酸三酯与第二个醇之间进行缩合，得到亚甲基双膦酸双酯。
