Abstract
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).
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Bacillus subtilis / enzymology
-
Bacterial Proteins / antagonists & inhibitors
-
Carbon / chemistry*
-
Carbon-Sulfur Lyases / antagonists & inhibitors
-
Dose-Response Relationship, Drug
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology
-
Homocysteine / analogs & derivatives*
-
Homocysteine / chemical synthesis
-
Homocysteine / chemistry
-
Homocysteine / pharmacology
-
Molecular Structure
-
Stereoisomerism
-
Structure-Activity Relationship
-
Sulfones / chemistry*
-
Sulfur / chemistry*
-
Vinyl Compounds / chemistry*
Substances
-
Bacterial Proteins
-
Enzyme Inhibitors
-
S-ribosyl-L-homocysteine
-
Sulfones
-
Vinyl Compounds
-
Homocysteine
-
Sulfur
-
Carbon
-
Carbon-Sulfur Lyases
-
LuxS protein, Bacteria