10.1021/jo960192+.s002 Reza Fathi Reza Fathi M. Jonathan Rudolph M. Jonathan Rudolph Robert G. Gentles Robert G. Gentles Rina Patel Rina Patel Eric W. MacMillan Eric W. MacMillan Michael S. Reitman Michael S. Reitman David Pelham David Pelham Alan F. Cook Alan F. Cook Synthesis and Properties of Combinatorial Libraries of Phosphoramidates American Chemical Society 1996 diversity elements combinatorial libraries drug discovery program nonradioactive labels chemical properties unfunctionalized diols monomeric units Combinatorial Libraries 32 phosphorus phosphoramidate derivatives 1996-08-09 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Properties_of_Combinatorial_Libraries_of_Phosphoramidates/3702240 We have assembled a set of combinatorial libraries of phosphoramidates for pharmacological evaluation. A range of functionalized and unfunctionalized diols, representing a variety of diversity elements, were converted into their corresponding dimethoxytrityl H-phosphonate derivatives which were coupled to each other to produce H-phosphonate dimers and trimers. The H-phosphonate diesters were converted into phosphoramidates by reaction with a wide range of primary and secondary amines. Very large libraries (theoretically, in excess of one million compounds) possessing five sites of diversity were generated for use in our drug discovery program. Smaller libraries with lower molecular weights were also prepared in which only two monomeric units were coupled together and converted into their phosphoramidate derivatives. Methods for the attachment of both radioactive and nonradioactive labels, including <sup>32</sup>phosphorus, tritium, and fluorescein, have been developed. Representative single sequences were also prepared and their chemical properties studied.