Synthesis and peptidyl group migration in isopropylidene acetals derived from the glucose-substituted imidazolidinone related to opioid peptide leucine-enkephalin

The reaction of the glucose-substituted imidazolidinone 1, structurally rel ated to endogenous opioid pentapeptide leucine-enkephalin (Tyr-Gly-Gly-Phe- Leu), with acetone in the presence of acid catalyst gives 2,3-O-isopropylid ene derivative 2 along with the isomeric monoacetal 3. Evidence is presente d by using RP HPLC and NMR spectroscopy that, under the conditions of ketal formation, the peptidyl group migrated from the primary (2) to the adjacen t secondary hydroxy group of the sugar moiety to give ester 3. The product distribution in the equilibrated reaction mixture (2 :3 approximate to 1.5 : 1) indicated that 5-O-peptidyl derivative 2 is slightly more stable than ester 3. Peptidyl group migration in aqueous solution at pH = 5 shows slow 2 --> 3 rearrangement and markedly faster 3 --> 2 conversion.