S-Ribosylhomocysteine analogues with the carbon-5 and sulfur atoms replaced by a vinyl or (fluoro)vinyl unit.
Treatment of the protected ribose or xylose 5-aldehyde with sulfonyl-stabilized fluorophosphonate gave (fluoro)vinyl sulfones. Stannyldesulfonylation followed by iododestannylation afforded 5,6-dideoxy-6-fluoro-6-iodo-d-ribo or xylo-hex-5-enofuranoses. Coupling of the hexenofuranoses with alkylzinc bromides gave 10-carbon ribosyl- and xylosylhomocysteine analogues incorporating a fluoroalkene. The fluoroalkenyl and alkenyl analogues were evaluated for inhibition of Bacillus subtilis S-ribosylhomocysteinase (LuxS). One of the compounds, 3,5,6-trideoxy-6-fluoro-d-erythro-hex-5-enofuranose, acted as a competitive inhibitor of moderate potency (K(I)=96microM).
Wnuk
Stanislaw F
SF
Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA. wnuk@fiu.edu
Lalama
Jennifer
J
Garmendia
Craig A
CA
Robert
Jenay
J
Zhu
Jinge
J
Pei
Dehua
D
D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D002244:Carbon / Q000737:chemistry*; D013437:Carbon-Sulfur Lyases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C487472:S-ribosyl-L-homocysteine; D013450:Sulfones; D014753:Vinyl Compounds; D006710:Homocysteine; D013455:Sulfur; D002244:Carbon; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria