Synthesis of N-(Hydroxy)amide- and N-(Hydroxy)thioamide-containing peptides
| Autor: | Phanstiel O th, Lu Wang |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
chemistry.chemical_classification
Fluorenes Magnetic Resonance Spectroscopy Chemistry Acylation Organic Chemistry Diastereomer Stereoisomerism Nuclear magnetic resonance spectroscopy Hydroxamic Acids Medicinal chemistry Amides chemistry.chemical_compound Amide Reagent Amines Amino Acids Peptides Racemization Thioamide |
| Zdroj: | The Journal of organic chemistry. 65(5) |
| ISSN: | 0022-3263 |
| Popis: | Methods developed with N-(benzoyloxy)amines and hydroxamic acids were used in the synthesis of N-(hydroxy)amide-containing pseudopeptides. Acylation of N-(benzoyloxy)phenethylamine with the acid chloride of N(alpha)-Fmoc-L-leucine provided a N(alpha)-Fmoc-N-(benzoyloxy)-L-leucinamide in 90% yield. Deprotection of the benzoyl group (using 10 vol % NH(4)OH/MeOH) provided the N(alpha)-Fmoc-N-(hydroxy)-L-leucinamide in 87% yield. In general, the appended Fmoc group allowed for further elaboration of the N-hydroxy-N-(alkyl)amides using classic peptide-coupling methods. A practical synthetic strategy was developed, and racemization issues were addressed using diastereomeric Val-Leu derivatives. In addition, N-(hydroxy)thioamides were generated from the corresponding N-(benzoyloxy)thioamides. N-(Benzoyloxy)thioamides were obtained in moderate yields (53-76%) from the reaction of the corresponding N-(benzoyloxy)amides with Lawesson's reagent (i.e., 2, 4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disu lfide). In summary, this new technology allows for the introduction of either N-hydroxyamide or N-(hydroxy)thioamide linkages into pseudopeptide chains without racemization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|