title: S-Ribosylhomocysteine Analogues Modified at the Ribosyl C-4 Position.
abstract: 4-C-Alkyl/aryl-S-ribosylhomocysteine (SRH) analogues were prepared by coupling of homocysteine with 4-substituted ribofuranose derivatives. The diastereoselective incorporation of the methyl substituent into the 4 position of the ribose ring was accomplished by addition of methylmagnesium bromide to the protected ribitol-4-ulose yielding the 4-C-methylribitol in 85% yield as single 4Rdiastereomer. The 4-Chexyl, octyl, vinyl, and aryl ribitols were prepared analogously. Chelation controlled addition of a carbanion to ketones from the (Si-face) was responsible for the observed stereochemical outcome. Oxidation of the primary alcohol of the 4-Cribitols with the catalytic amount of tetrapropylammonium perruthenate in the presence ofN-methylmorpholineN-oxide produced 4-C-alkylribono-1,4-lactones in high yields. Mesylation of the latter compounds at the 5-hydroxyl position and treatment with a protected homocysteine thiolate afforded protected 4-C-alkyl/aryl-SRH analogues as the lactones. Reduction with lithium triethylborohydride and successive global deprotections with TFA afforded 4-C-alkyl/aryl SRH analogues. These analogues might impede theS-ribosylhomocysteinase(LuxS)-catalyzed reaction by preventing β-elimination of a homocysteine molecule, and thus depleting the production of quorum sensing signaling molecule AI-2.
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Christiane
authors: C
authors: Chbib
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Adam J
authors: AJ
authors: Sobczak
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Mukesh
authors: M
authors: Mudgal
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Cesar
authors: C
authors: Gonzalez
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Daniel
authors: D
authors: Lumpuy
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Justyna
authors: J
authors: Nagaj
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Kamila
authors: K
authors: Stokowa-Soltys
authors: Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
authors: Stanislaw F
authors: SF
authors: Wnuk
keywords: C-substituted ribose; Homocysteine; LuxS; S-Ribosylhomocysteine; ribonolactone