Synthetic approaches to peptide analogues containing 4, 4-difluoro-L-proline and 4-keto-L-proline.
An improved synthesis of 4, 4-difluoro-L-proline is described. A key step in this synthesis involves the fluorination of Z-4-keto-L-proline benzyl ester, using diethylaminosulfur trifluoride (DAST), to give the corresponding Z-4, 4-difluoro-L-proline benzyl ester. Preparation of dipeptide derivatives containing 4, 4-difluoro-L-proline has been accomplished by initial synthesis of the corresponding 4-keto-L-proline depeptide derivatives, which were then fluorinated with DAST. A one-step synthesis of Boc-4-keto-L-proline from Boc-4-hydroxy-L-proline by chromium trioxide oxidation is reported. These synthetic procedures should facilitate the preparation of a variety of peptide analogues containing 4, 4-difluoro-L-proline and 4-keto-L-proline.
D004151:Dipeptides / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D011392:Proline / Q000031:analogs & derivatives*
D004151:Dipeptides; D007202:Indicators and Reagents; C036784:4-ketoproline; C036785:4,4-difluoroproline; D011392:Proline