title: Syntheses and antimycobacterial activities of [(2S,3R)-2-(amino)-4-(arenesulfonamido)-3-hydroxy-1-phenylbutane derivatives.
abstract: The syntheses of hydroxyethylsulfonamides, (2S,3R)-tert-butyl N-[4-(N-benzyl-4-R-phenylsulfonamido)-3- hydroxy-1-phenylbutan-2-yl]carbamates and (5) (2S,3R)-2-amino-4-[N-benzyl-4-R-benzenesulfonamido]-3-hydroxy-1- phenylbutane hydrochlorides (6), derived from (2S,3S)-Boc-phenylalanine epoxide, are reported. None of the compounds, containing the Boc group, showed activity against M. tuberculosis ATTC 27294, while compounds 6 did, with the most active compounds having R = p-Cl, p-Br and p-Me. Results indicate that the presence of a free amino group at C2 and the sulphonamide moiety are important for biological activity. The antimycobacterial activity of compounds 6 correlated well with the calculated lipophilicities, but not with the electronic effects of the substituents, R. All compounds 6 were highly cytotoxic against the hepatoma cell lineage Hep G2 A16. The X-ray crystal structure of compound [(6: R = Me).H2O] is also reported. In the propeller-like conformation adopted by the cation, the amino and hydroxy groups have a cis arrangement, and thus are suitably placed to form 5- membered chelates.
authors.forename: Marcele
authors.initials: M
authors.lastname: Moreth
authors.forename: Claudia R B
authors.initials: CR
authors.lastname: Gomes
authors.forename: Maria C S
authors.initials: MC
authors.lastname: Lourenço
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Soares
authors.forename: Marcele N
authors.initials: MN
authors.lastname: Rocha
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Kaiser
authors.forename: Marcus V N
authors.initials: MV
authors.lastname: de Souza
authors.forename: Solange M S V N
authors.initials: SM
authors.lastname: Wardell
authors.affiliation: Centro de Desenvolvimento Tecnologico em Saude (CDTS), Fundacao Oswaldo Cruz (FIOCRUZ), Casa Amarela, Av. Brasil 4365, 21040-900, Rio de Janeiro, RJ, Brazil. j.wardell@abdn.ac.uk.
authors.forename: James L
authors.initials: JL
authors.lastname: Wardell
mesh_terms: D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000605:Amino Alcohols; D000900:Anti-Bacterial Agents; D013449:Sulfonamides