-Ribosylhomocysteine Analogues Modified at the Ribosyl C-4 Position.

4--Alkyl/aryl--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--methylribitol in 85% yield as single 4 diastereomer. The 4- hexyl, octyl, vinyl, and aryl ribitols were prepared analogously. Chelation controlled addition of a carbanion to ketones from the (-face) was responsible for the observed stereochemical outcome. Oxidation of the primary alcohol of the 4- ribitols with the catalytic amount of tetrapropylammonium perruthenate in the presence of -methylmorpholine -oxide produced 4--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--alkyl/aryl-SRH analogues as the lactones. Reduction with lithium triethylborohydride and successive global deprotections with TFA afforded 4--alkyl/aryl SRH analogues. These analogues might impede the -ribosylhomocysteinase(LuxS)-catalyzed reaction by preventing β-elimination of a homocysteine molecule, and thus depleting the production of quorum sensing signaling molecule AI-2.