Abstract
Cinnamaldehyde derivatives were synthesized in good to excellent yields in one step by a mild and selective, base-free palladium(II)-catalyzed oxidative Heck reaction starting from acrolein and various arylboronic acids. Prepared α,β-unsaturated aldehydes were used for synthesis of novel α-aryl substituted fosmidomycin analogues, which were evaluated for their inhibition of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase. IC(50) values between 0.8 and 27.3 μM were measured. The best compound showed activity comparable to that of the most potent previously reported α-aryl substituted fosmidomycin-class inhibitor.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acrolein / analogs & derivatives*
-
Acrolein / chemical synthesis
-
Acrolein / chemistry
-
Aldose-Ketose Isomerases / antagonists & inhibitors*
-
Aldose-Ketose Isomerases / chemical synthesis*
-
Antitubercular Agents / chemical synthesis*
-
Antitubercular Agents / chemistry*
-
Antitubercular Agents / pharmacology
-
Catalysis
-
Fosfomycin / analogs & derivatives*
-
Fosfomycin / chemical synthesis
-
Fosfomycin / chemistry
-
Fosfomycin / pharmacology
-
Humans
-
Inhibitory Concentration 50
-
Models, Molecular
-
Multienzyme Complexes / antagonists & inhibitors*
-
Multienzyme Complexes / chemical synthesis*
-
Mycobacterium tuberculosis / chemistry*
-
Mycobacterium tuberculosis / drug effects
-
Mycobacterium tuberculosis / enzymology
-
Oxidation-Reduction
-
Oxidoreductases / antagonists & inhibitors*
-
Oxidoreductases / chemical synthesis*
-
Palladium / chemistry
-
Protein Binding
Substances
-
Antitubercular Agents
-
Multienzyme Complexes
-
Fosfomycin
-
fosmidomycin
-
Palladium
-
Acrolein
-
Oxidoreductases
-
1-deoxy-D-xylulose 5-phosphate reductoisomerase
-
Aldose-Ketose Isomerases
-
cinnamaldehyde