Synthesis of a complete series of C-4 fluorinated Phe-Gly mimetics

The complete series of Boc-protected allylic mono- and difluorinated Phe-Gly methyl ester derivatives has been synthesized using facile methods. Diastereomeric allylic alcohol derivatives were used as key intermediates, cis- And trans-aziridine derivatives were synthesized in high yields from the diastereomeric alcohols using Mitsunobu conditions. The aziridines were treated with diethylaminosulfur trifluoride (DAST) at room temperature, which resulted in stereoselective ring openings yielding the monofluorinated derivatives. The difluorinated isostere was synthesized from the gamma-keto ester derivative using DAST. Also the corresponding series of saturated fluorinated derivatives was synthesized. (C) 1999 Elsevier Science Ltd. All rights reserved.