Enantiomer-selective solvolysis catalysed by a histidine-containing cyclic dipeptide carrying chiral side chain

Tripeptides with cyclic dipeptide backbones, cyclol-Glu(l-Leu-O Bzl)-t-His] and cyclol-Glu(l-Leu-OH)-Ir His, and the corresponding tripeptides with linear backbones, Me₃COCO-l-Glu(l-Leu-OBzl)-l-His-OMe and Me₃COCO-l-Glu(l-Leu-OH)-l-His-OMe, were synthesized and used as catalysts for the hydrolysis of carboxylic acid active esters of various types. The experimental results are summarized as follows. (I) In the hydrolysis of a neutral and hydrophobic substate, p-nitrophenyl laurate, in 20% dioxane/H₂O mixture of pH 7.8, a hydrophobic and flexible peptide, Me₃COCO-l-Glu(l-Leu-OH)-l-His-OMe, was more reactive than imidazole. On the other hand, cyclol-Glu(l-Leu-OBzl)-l-His] and cyclol-Leu-OH)-l-His], which have rigid backbone chain and fixed sidechain conformation, were not particularly reactive. (2) in the solcolysis of a positively charged substrate, p-nitrophenyl glycinate hydrochloride, in 42% i-PrOH/H₂O mixture at pH 6.95, a positively charged substrate, p-nitrophenyl glycinate hydrochloride, in 42% i-PrOH/H₂O mixture at pH 6.95, a negatively charged and flexible peptide, Me₃COCO-l-Glu(l-Leu-OH)-l-His-OMe, was more reactive than imidazole. However, cyclo l-Glu(l-Leu-OH)-l-His] was not particularly reactive in the same reaction. In the hydrolysis of p-nitrophenyl glycinate hydrochloride in aqueous solution at pH 7.8 a hydrophobic and rigid peptide, cyclo(l-Glu(l-Leu-OBzl)-l-His], was more reactive than imidazole. However, in the hydrolysis of p-nitrophenyl CO-AMINODODECANOATE hydrochloride, which has a positive charge and a rective site separated by a long hydrophobic chain, peptide catalysts did not show efficient catalysis. (3) In the hydrolysis of a positively charged, hydrophobic and chiral substrate, p-nitrophenyl leucinate hydrochloride, in aqueous solution at pH 6.95, the d-enantiomer was hydrolysed more quickly that the t-enantiomer with cyclol-Glu(l-Leu-OBzl)l-His] or cyclot-Glu(l-Leu-OH)-l-His] as catalyst. On the other hand, the tripeptides with linear backbone did not effect an enantiomer-selective catalysis. The solvolytic reaction catalysed by the tripeptides with cyclic dipeptide backbone in 42% i-PrOH/water mixture was also enantiomer-selective.