SYNTHESIS OF TRANS-EPOXY-L-PROLINE AND CIS-AZIRIDINO-L-PROLINE FROM S-PYROGLUTAMIC ACID - REGIOSELECTIVE AND DIASTEREOSELECTIVE RING-OPENING OF ITS DERIVATIVES

The pyroglutamic acid derivative 4 was converted through several steps into 2S,3R,4S-epoxyproline 8. Key steps of the reaction sequence were the stereoselective epoxidation of 4 to 5 and the chemoselective redu ction of the amide group of 5 with concomitant transformation of the a cetal moiety into the N-benzyl protecting group without oxirane ring o pening. The air sensitive benzyl derivative was transformed to the sta ble N-Boc prolinol derivative 6. Oxidation of 6 gave the protected epo xyproline derivative 7. Deprotection of 7 furnished enantiopure 2S,3R, 4S-epoxyproline 8. Ring opening of the oxirane 6 or 16 was accomplishe d with C, N, Cl-nucleophiles under complete regiocontrol. Azidoprolino l 9 served as a starting material for the synthesis of epiminoproline derivative 23. (C) 1997 Elsevier Science Ltd.