Hydrazides of N-blocked amino acids as sole substrates with unique difunctional behavior under papain catalysis |
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Authors: | John Leo Abernethy Gary F Kuzmin Charles M Lovett Jr William A Wilson |
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Institution: | Department of Chemistry, California State Polytechnic University, Pomona, California 91768 USA |
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Abstract: | Hydrazides of five N-acylamino acids have been used alone as substrates for papain catalysis to yield N1,N2-diacylhydrazines. With the exception of N-(benzyloxycarbonyl)(Z)-
-alanine hydrazide, they were very effective as both acylating agents of the enzyme and nucleophiles in attacking the enzyme-substrate intermediate. Although Z-
-alanine hydrazide was a minimal acylating agent, it was a satisfactory nucleophile. The most favorable reaction involved Z-
-alanine hydrazide in producing N1,N2-bis(Z-
-alanyl)hydrazine. When Z-
-alanine hydrazide was the substrate, this same chiral diacylhydrazine was formed along with meso N1-(Z-
-alanyl)-N2-(Z-
-alanyl)hydrazine. For the acylation step, the enzyme displayed powerful, essentially stereospecific, bias toward the
enantiomer. Once the thioester intermediate was formed, little preference was detected for attack by the enantiomers as nucleophiles. The most direct procedure for synthesis of substrates was conversion of Z-amino acids to their esters by means of dry HCl in an absolute alcohol. Treatment with hydrazine produced the hydrazides in excellent yield. |
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