RESUMO
A fast and facile synthesis of a series of 4-nitrophenyl 2-azidoethylcarbamate derivatives as activated urea building blocks was developed. The N-Fmoc-protected 2-aminoethyl mesylates derived from various commercially available N-Fmoc-protected α-amino acids, including those having functionalized side chains with acid-labile protective groups, were directly transformed into 4-nitrophenyl 2-azidoethylcarbamate derivatives in 1 h via a one-pot two-step reaction. These urea building blocks were utilized for the preparation of a series of urea moiety-containing mitoxantrone-amino acid conjugates in 75-92% yields and parallel solution-phase synthesis of a urea compound library consisted of 30 members in 38-70% total yields.
Assuntos
Aminoácidos/química , Fluorenos/química , Nitrofenóis/química , Bibliotecas de Moléculas Pequenas/química , Ureia/análogos & derivados , Uretana/análogos & derivados , Aminoácidos/síntese química , Azidas/síntese química , Azidas/química , Técnicas de Química Combinatória/economia , Técnicas de Química Combinatória/métodos , Fluorenos/síntese química , Micro-Ondas , Nitrofenóis/síntese química , Bibliotecas de Moléculas Pequenas/síntese química , Ureia/síntese química , Uretana/síntese químicaRESUMO
Isotope-edited IR of proteins has generated considerable interest. Double labeling with 13C and 18O with high levels of isotopic enrichment is required for residue-specific resolution. Current methods for the preparation of doubly labeled amino acids give modest 18O enrichment, limiting the utility of the approach. We report a simple and economical method for preparing 13C,18O-doubly labeled N-(9-fluorenylmethoxycarbonyl)amino acids with high levels of enrichment for residues that do not require acid-labile side-chain protecting groups.