Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing

We recently reported the use of PSCl3 for the thiophosphorylation of alkylamines where the resulting N-thiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156-6158.). Herein we report the development of this methodology using amino acid, amino sugar, aminonucleoside and aniline substrates. The hydrolysis properties of N-thiophosphoramidate ions and their reactivities towards alkylating agents are also explored. In addition, we demonstrate the application of our approach to the preparation of a small library of compounds, including quinoline-based N,S-dialkylthiophosphoramidates which were tested for antileishmanial activity.This is the peer-reviewed version of the following article: Trmcic, M. and Chadbourne, F.L. and Brear, P.M. and Denny, P.W. and Cobb, S.L. and Hodgson, D.R.W., 2013. Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. Organic and biomolecular chemistry. 11, 2660-2675. [http://doi.org/10.1039/c3ob27448a]Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3468