Application of the Ugi reaction for the one-pot synthesis of uracil polyoxin C analogues.
A simple, two-step synthesis of amide derivatives of uracil polyoxin C (UPOC) methyl ester using the Ugi reaction is described. The four components employed in the Ugi reaction are 2',3'-isopropylidine-protected uridine-5'-aldehyde, 2,4-dimethoxybenzylamine, an isoxazolecarboxylic acid, and the convertible isonitrile N-(2-{[(tert-butyldimethylsilyl)oxy]methyl}phenyl)carbonitrile. Following the Ugi reaction, treatment with HCl in MeOH achieves deprotection of the isopropylidene group and the N-benzyl group and conversion of the isonitrile-derived amide (the Ugi product) into the corresponding methyl ester. The procedure is amenable to automated multiparallel synthesis of novel compounds related to the polyoxin and nikkomycin nucleoside-peptide antibiotics.
Plant
Andrew
A
Centre for Chemical Biology, Richard Roberts Building, Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK. andrew.plant@syngenta.com
Thompson
Peter
P
Williams
David M
DM
D002384:Catalysis; D002686:Chitin / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D011741:Pyrimidine Nucleosides; C414026:uracil polyoxin C; D002686:Chitin; D014498:Uracil