Histidine anhydrides

Treatment of bovine heart bci complex with ethoxyformic anhydride (EFA), which is known to modify amino acid residues covalently (preferentially histidine residues), inhibits electron transfer and has an effect on the EPR spectra of the Rieske cluster comparable to that observed upon addition of stigmatellin, that is, a decrease in rhombicity (80). This further supports the suggestion that quinones as well as quinonoid inhibitors interact directly with the histidine ligands of the Rieske cluster. 

Protein functional groups able to react with anhydrides include the oc-amines at the N-terminals, the s-amine of lysine side chains, cysteine sulfhydryl groups, the phenolate ion of tyrosine residues, and the imidazolyl ring of histidines. However, acylation of cysteine, tyrosine, and histidine side chains forms unstable complexes that are easily reversible to regenerate the original group. Only amine functionalities of proteins are stable to acylation with anhydride reagents (Fraenkel-Conrat, 1959 Smyth, 1967). 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

HC Beyerman, J Hirt, P Kranenburg, JLM Syrier, A van Zon. Excess mixed anhydride peptide synthesis with histidine derivatives. Rec Trav Chim Pays-Bas 93, 256, 1974. 

Histidine forms a diacyl derivative that is apparently unstable. Moodie has suggested the use of ethoxyformic anhydride to form the stable Na-trifluoroacetyl-Nim-carbethoxy n-butyl histidinate with no accompanying unstable by-products (44). 

Treating ovotransferrin and human serum transferrin with 170-400 molar excess of ethoxyformic anhydride resulted in complete ethoxy-formylation of histidines with complete loss in iron-binding activity (33). The binding of each iron (two iron-binding sites per protein molecule) protected two histidines from ethoxyformylation, and in both cases the proteins remained completely active. These results plus kinetic analyses of the inactivations indicated two essential histidines in each binding site. Ethoxyformic anhydride also may react with amino groups. 

Trifluoroacetic acid or trifluoroacetic acid anhydride reacts with hydrox-amic acid amides, thiosemicarbazide, and 1,2-diaminopyridine to yield herbicidal active 1,2,4-oxadiazoles [78GEP(0)2801509], fungicidal-active 1,3,4-thiadiazoles (80USP4264616), and 2-trifluoromethyltriazolo[l,5-alpyridines [80JFC(15)179. 2-Trifluoromethyl-L-histidine was obtained from L-histidine on treatment with benzoyl chloride/sodium hydroxide and subsequent ring closure with trifluoroacetic anhydride (78JOC3403) (Scheme 41). 

Another possible aspect of histidine peptide cleavage is introduced by the great lability of 4(5H)-imidazolones (CXXXIII) (Freter el al., 19.57 Brown and Kies, 1959). In their lability and eagerness to open up to forma-raidino acids (CXXXIV) they almost resemble anhydrides (Kny and Witkop, 1959). It is not unlikely that such 4(5H)-imidazolones can be produced nonenzymatically. Such selective oxidation of a histidine peptide to a 4(5H)-imidazolone derivative introduces the possibility of translacta-... 

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... 

The catalysis of hydrolysis of carboxylic acid derivatives by weak bases has not been carefully studied until relatively recently. Koshland reported in 1952 the catalysis of acetyl phosphate hydrolysis by pyridine Bafna and Gold (1953) reported the pyridine-catalyzed hydrolysis of acetic anhydride. A short time later the catalysis of aromatic ester hydrolysis by imidazole was demonstrated (Bender and Turnquest, 1957 a, b Bruice and Schmir, 1957). Since that time a large amount of work has been devoted to the understanding of catalyzed ester reactions. Much of the work in this area has been carried out with the purpose of inquiry into the mode of action of hydrolytic enzymes. These enzymes contain on their backbone weak potential catalytic bases or acids, such as imidazole in the form of histidine, carboxylate in the form of aspartate and glutamate, etc. As a result of the enormous effort put into the study of nucleophilic displacements at the carbonyl carbon, a fair understanding of these reactions has resulted. An excellent review is available for work up to 1960 (Bender, 1960). In addition, this subject has been... 

Kemp et al have now published complete details on the use of this reagent for peptide synthesis. The second step is best carried out with a tetraalkylam-monium salt of an amino acid or with an amino acid (or peptide) in DMSO containing 1 eq. of tetramethylguanidine, [(CH3)2N]2C=NH. The method has been shown to be useful with all the common amino acids except arginine and histidine. Medium-sized peptides have been prepared. Kemp concludes that this method is comparable to the azide, carbodiimide, and mixed-anhydride methods of peptide synthesis. Difficulties with yield and purification have been observed with fairly large peptides. 

Mit anderen Aminosauren ist Histidin zur Bildung von Diketo-piperazinen befahigt. Das Anhydrid von Prolin und Histidin z.B. findet sich im menschlichen Ham (247). 

---