Syntheses and Antimycobacterial Activities of [(2S,3R)-2-(Amino)-4- (Arenesulfonamido)-3-Hydroxy-1-Phenylbutane Derivatives

Marcele      Moreth; Claudia   R.B.   Gomes; Maria   C.S.   Lourenco; Rodrigo   P.   Soares; Marcele   N.   Rocha; Carlos   R.   Kaiser; Marcus   V.N.   de Souza; Solange   M.S.V.N.   Wardell; James   L.   Wardell

doi:10.2174/15734064113099990003

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.

Keywords: Antimycobacterial activity, cytotoxicity, hydroxyethylamine derivatives, sulfonamide derivatives, x-ray crystallography.

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