Combined Phosphoramidite-Phosphodiester Reagents for the Synthesis of Methylene Bisphosphonates.
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.
Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Sander B
SB
Engelsma
Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Nico J
NJ
Meeuwenoord
Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Hermen S
HS
Overkleeft
Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Gijsbert A
GA
van der Marel
Leiden Institute of Chemistry, Department of Bioorganic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Dmitri V
0000-0002-6978-7425
DV
Filippov
methylene bisphosphonates; phosphanylmethylphosphonate; phosphorylation; pyrophosphate bioisosteres; solid-phase synthesis