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Combined Phosphoramidite‐Phosphodiester Reagents for the Synthesis of Methylene Bisphosphonates
Author(s) -
Engelsma Sander B.,
Meeuwenoord Nico J.,
Overkleeft Hermen S.,
van der Marel Gijsbert A.,
Filippov Dmitri V.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201611878
Subject(s) - methylene , chemistry , phosphoramidite , reagent , phosphonate , bisphosphonate , alcohol , phosphodiester bond , combinatorial chemistry , organic chemistry , oligonucleotide , medicine , dna , rna , biochemistry , osteoporosis , gene , endocrinology
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.