Histidine methyl ester

A/- -toluene su1fony1)-T-phenylalanine (62), L-histidine methyl ester (63), A/-acetyl L-valine /-butyl amide (64), etc, are used as chiral addends. 

Figure 8.43 Separation of enantiomers using complexation chromatography. A, Separation of alkyloxiranes on a 42 m x 0.2S mm I.O. open tubular column coated with 0.06 M Mn(II) bis-3-(pentafluoro-propionyl)-IR-camphorate in OV-ioi at 40 C. B, Separation of D,L-amino acids by reversed-phase liquid chromatography using a mobile phase containing 0.005 M L-histidine methyl ester and 0.0025 M copper sulfate in an ammonium acetate buffer at pH 5.5. A stepwise gradient using increasing amounts of acetonitrile was used for this separation.

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

This reaction is known to be catalyzed by the enzyme oxynitrilase to produce the optically pure cyanohydrin 76). Since this reaction proceeds with a base catalyst, Jnoue et al. 75) used cyclic and linear dipeptides containing (S)-histidine. The catalysts employed are as follows benzyloxycarbonyl-R-(S)-histidine methyl ester with R = (S)-alanyl, (R)-alanyl, (S)-phenylalanyl,[Z-(S)-Ala-(S)-His-OCH3, Z-(R)-Ala-(S)-His-OCH3, and Z-(S)-Phe-(S)-His-OCH3] as linear dipeptides, and cyclic (S)-histidine containing dipeptides Gly—(S)—His,... 

More detailed studies of reactions of this type have been reported.96,97 Nickel(II) complexes of histidine and tryptophan provide stereoselectivity in the hydrolysis of histidine methyl ester, but stereoselectivity is not observed with nickel(Il) complexes of aspartic acid or methionine. Only tridentate ligands with a minimum steric bulk appear to be capable of exhibiting stereoselectivity in reactions of this type. 

Another example, which demonstrates the modulation of the peroxidase activity of Mb by modification of the heme-propionate side chains, has been proposed by Casella and co-workers (75). They prepared a Mb reconstituted with peptide-linked hemin such as protohemin-L-arginyl-L-alanine or protohe-min-L-histidine methyl ester as shown in Fig. 20. The peroxidase activity toward small substrate oxidations by the reconstituted Mb slightly increased the fccat... 

For histidine methyl ester and histidinamide, the carboxylic acid group is blocked. The NA,N(3)-chelate complex forms slowly when these molecules react with a solution of 6. In the reaction of 6 with histidylglycine (Scheme 11), the carboxylate group binds first to give 42, then there is a slow reaction to form the NA,N(3)-che ate complex 43. If there is an excess of 6 present, the free carboxylate binds to another diammineplatinum unit (44), followed by ring closure to 45 [33]. 

Chiral calix[4]arene podands were made using A-benzyl histidine methyl ester.33 These histidyl calixarenes 12a,b were studied in complexation experiments with Co(H), but no use was made of their chirality. The same is true for a chiral calix[4]arene capped tetraphenyl porphyrin which is C4-symmetrical due to the four L-alanine derived linkers.34... 

Trimethylsilyl chloride also gives the N -product alone in simple models, but this is probably the consequence of thermodynamic control in any event N -trialkylsilyl derivatives are much too labile to be useful as stepping stones to N"-alkylhistidines. The only thoroughly studied example of exclusive mono-N -derivatization is the reaction of acetic anhydride with acylhistidine esters, when thermodynamic control appears to operate. Thus, N -(benzyl-oxycarbonyl)histidine methyl ester gives only the M-acetyl derivative, providing a third kind of intermediate which is useful for N"-alkylation with reactive halides (see Section 2.6.2.3).1 1... 

This amino acid which is synthesized by muscle and excreted into urine without recycling has been methylated with [Djj-methyl iodide exclusively at N site and applied as tracer in vivo and as an isotopic dilution standard in vitro, by protecting the N and N positions in a cyclic urea derivative 34. The latter was obtained by treating the (5)-histidine methyl ester 35 with carbonyl diimidazole and hydrolysing the product 36 in boiling dilute hydrochloric acid to give isomerically and isotopically pure title compound 37 retaining at least 95% of its optical rotation (equation 5). 37 has been applied in clinical research. 

PHME pyridoxyl-histidine methyl ester conjugate... 

An alternative strategy for binding amines is to use a Lewis acidic metal atom. Zn-porphyrin complexes prove especially useful in this context. For example, the doubly bridged a,a,p,P-systern 12 bound the methyl esters of a-amino acids with moderate but fairly general enantio-selectivities (7.5 1 for valinate, 4 1 for alaninate) in dichloromethane. The Troger s-base-linked bis-porphyrin 13 was designed to make two ZimA interactions and was shown to bind histidine methyl ester 14 with an enantioselectivity of 13 1 in CDCls. Recently, the... 

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