title: Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing.
abstract: 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.
authors: Department of Chemistry, Science Laboratories, Durham University, South Road, Durham, DH1 3LE, United Kingdom.
authors: Milena
authors: M
authors: Trmčić
authors: Frances L
authors: FL
authors: Chadbourne
authors: Paul M
authors: PM
authors: Brear
authors: Paul W
authors: PW
authors: Denny
authors: Steven L
authors: SL
authors: Cobb
authors: David R W
authors: DR
authors: Hodgson
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000477:Alkylating Agents / Q000737:chemistry; D000478:Alkylation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000138:chemical synthesis / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D005944:Glucosamine / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007894:Leishmania mexicana / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D010649:Phenylalanine / Q000138:chemical synthesis / Q000737:chemistry; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010766:Phosphorylation; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000477:Alkylating Agents; D000577:Amides; D000814:Aniline Compounds; D000981:Antiprotozoal Agents; D003839:Deoxyadenosines; D010756:Phosphoric Acids; D013438:Sulfhydryl Compounds; C016272:N-bromoacetamide; C057928:5'-amino-5'-deoxyadenosine; C002546:5'-amino-5'-deoxyguanosine; D010649:Phenylalanine; C011067:phosphoramidic acid; D003849:Deoxyguanosine; D005944:Glucosamine; C023650:aniline