title: Synthesis of functionalized cinnamaldehyde derivatives by an oxidative Heck reaction and their use as starting materials for preparation of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase inhibitors.
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.
authors.affiliation: Division of Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Anneli
authors.initials: A
authors.lastname: Nordqvist
authors.forename: Christofer
authors.initials: C
authors.lastname: Björkelid
authors.forename: Mounir
authors.initials: M
authors.lastname: Andaloussi
authors.forename: Anna M
authors.initials: AM
authors.lastname: Jansson
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Mowbray
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Mats
authors.initials: M
authors.lastname: Larhed
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis*; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis*; D010165:Palladium / Q000737:chemistry; D011485:Protein Binding
chemical_list: D000995:Antitubercular Agents; D009097:Multienzyme Complexes; D005578:Fosfomycin; C024640:fosmidomycin; D010165:Palladium; D000171:Acrolein; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases; C012843:cinnamaldehyde