Pyridoxal derivatives

Pyridoxal Derivatives. Various aldehydes of pyridoxal (Table 3) react with hemoglobin at sites that can be somewhat controlled by the state of oxygenation (36,59). It is thereby possible to achieve derivatives having a wide range of functional properties. The reaction, shown for PLP in Figure 3, involves first the formation of a Schiff s base between the amino groups of hemoglobin and the aldehyde(s) of the pyridoxal compound, followed by reduction of the Schiff s base with sodium borohydride, to yield a covalendy-linked pyridoxyl derivative in the form of a secondary amine. 

Table 2. Observed rate constants for the transamination of pyruvate to alanine mediated by various pyridoxal derivatives...

Dependence of tyrosine, lysine, arginine and ornithine decarboxylase on a phosphorylated pyridoxal derivative shown. 6, 8... 

Non-dependence of glutamate and histidine decarboxylases on a phosphorylated pyridoxal derivative suggested. 6... 

Phosphorylated pyridoxal derivative proved to be pyridoxal 5 -phosphate. 9... 

Another chiral aldehyde suitable for such transformations is the recently prepared pyridoxal derivative (121).323 Even more recent examples of chiral carbonyl compounds (122) have been used for the partial resolution of amino acids. The enantiomers of compounds (122) undergo reaction with racemic a-amino acids and copper(II) ions to give preferential formation of enantiomeric copper complexes. The ( -enantiomers of (122) preferentially form complexes containing the... 

Method. Solutions of amino acids in phosphate buffer (pH 9.3) are mixed with an equal volume of freshly prepared 0.4 M pyridoxal solution (adjusted to pH 9.3) and permitted to stand at 8 °C for 30 min. (The molar ratio of pyridoxal to amino acid should be >75 1.) At this point, 1 ml of sodium tetrahydroborate solution (100 mg/ml in 0.1 N sodium hydroxide) is added and the contents are gently shaken. Excess of sodium tetrahydroborate is destroyed by addition of sufficient hydrochloric acid (pH 1-2) prior to column chromatography. The pyridoxal derivatives are separated on a column (100 X 0.6 cm) of Aminex A-5 ion-exchange resin (Bio-Rad) at a mobile phase flow-rate of 33 ml/h. The eluting solvents consist of 0.2 N buffers at pH 3.40,4.44 and 4.86 and a 0.35 N buffer at pH 5.86 (all of the buffers are sodium citrate). The separation of a number of pyridoxyl-... 

Participation of proton-donors other than hydroxonium ion has been observed, e.g. for phenylglyoxylic (59) and pyruvic (60) acids, for substituted benzaldehydes (61—63), unsaturated acids (49, 64), N-nitros-amines (65), nitrones (66), unsaturated ketones (67), aryl alkyl ketones (68) and various heterocyclic compounds (69, 70). Consecutive dissociation has been observed for maleic and fumaric acids (48), for phthalic acid (50) and for pyridoxal derivatives (71). 

Vitamins, cofactors, and metals have the potential to broaden the scope of antibody catalysis considerably. In addition to hydrolytic and redox reactions, they facilitate many complex functional group interconversions in natural enzymes.131 Pyridoxal, for example, plays a central role in amino acid metabolism. Among the reactions it makes possible are transaminations, decarboxylations, racemizations, and (3,y-eliminations. It is also essential for ethylene biosynthesis. Not surprisingly, then, several groups have sought to incorporate pyridoxal derivatives into antibody combining sites. 

Murakami et al. also examined the enantioselectivity of the catalyzed transamination reaction in a bilayer membrane [26]. They contrasted a system composed of a peptide lipid bearing an L-lysine residue (34), a hydrophobic pyridoxal derivative quaternized at the pyridyl nitrogen (37), and Cu(ii) ions. This system exhibited turnover behavior for... 

We next synthesized the pyridoxal-bound fl-CD catalyst 44 (Scheme 2.8) [43], which produced 3-5 times more tryptophan when incubated with indole, [f-chloroalanine, and A12(S04)3 (pH 5.2 and 100°C) than the reaction in which the pyridoxal derivative was replaced by simple pyridoxal. However, tryptophan yield was still only a few percent. As expected, this kinetic advantage disappeared at higher indole concentrations due to saturation of the binding site. Furthermore, L-tryptophan was produced in ca. 10% excess relative to the D-enantiomer. 

Kuzuhara et al. synthesized an optically resolved pyridoxal analog having an ansa chain" between the 2 - and 5 -positions (45) [46]. The aldolase-type reaction of 45 and glycine with either acetaldehyde or propionaldehyde afforded the corresponding P-hy-droxy-a-amino acid with 27-77% ee. The erythro isomers were 1.2-1.8 times dominant over threo ones. The (S) -enantiomer of the pyridoxal derivative furnished the (S)-amino acid in excess. Accordingly, the reaction occurred on the same face as was occupied by the ansa chain. We have confirmed these results [47]. 

Murakami et al. have utilized Mayer vesides to study aldolase-type reactions [48]. Formation of [i-phenylserinc from glydne and benzaldehyde proceeded effectively by cooperative catalysis of a hydrophobic pyridoxal derivative (47) and Zn(n) ions in the bilayer vesicle formed with 32. The threo isomer was dominantly produced over the erythro form. A marked enantioselectivity was observed in the co-veside of 32 and 35 in combination with 47 and Cu(ii) the ee for formation of (2S,3R)-P-phcnylscrinc over its enantiomeric (2R,3S)-isomer was 58%. Enantioselectivity also arose with another bilayer assembly, formed with 32, 35, and 37 in the presence of Cu(ii), where the (2R,3S) isomer was dominant over the (2S,3R) species in 13% ee. The opposite enantioselectivity performed by the second system, as compared with that for 47, might reflect a different stereochemical environment around the quinoid intermediate that allows the attack of benzaldehyde. 

Acylated pyridoxal derivatives, (IV), prepared by Haque (6) were effective in the treatment of cardiovascular hypertrophy, hypertension, and congestive heart failure. 

Pyridoxal-derived isoquinolines, 160-162 Pyrrolidines, 252-253 Pyrrolizidine oximes, 249-251 Pyrrolizidines, 225-228 biological activity, 226... 

Synthetic samples of (4 S)- and (4 i )-[4 - Hi]- and [4 - Hi]pyridoxamine 20a were prepared by the route outlined in Scheme 11, the key step being reduction of the labeled pyridoxal derivatives 32 with alpine boranes (32). 

By analogy to the metal-ion-catalyzed reaction of pyridoxal derivatives with nucleophiles, e.g., imine formation (24), it is highly hkely that the reduction proceeds via the 3-hydroxypyridine-4-carboxaldehyde-metal ion complex. Coordination of the carbonyl oxygen both in the ground state and in the transition state is envisaged to facilitate hydride transfer by decreasing the electron density on the carbonyl carbon. 

Finally, the three-carbon side chain of the indole-3-glycerolphosphate is removed to produce indole itself and glyceraldehyde-3-phosphate (Scheme 12.25). The indole moves from one subunit of the enzyme, tryptophan synthase (EC 4.2.1.20), to another where it encounters the result of dehydration of a pyridoxal-bound serine (Ser, S) to which it adds. Then, hydrolytic cleavage of the resulting pyridoxal derivative of tryptophan (Trp, W) yields pyridoxal, ready for another reaction with, for example, serine (Ser, S) and tryptophan (Trp, W). 

Liu, L., Rozemnan, M. and Breslow, R., Stereoselectivity in reactions of amino acids catalyzed by pyridoxal derivatives carrying rigidly-attached chirally-mounted basic groups transamination, racemization. 

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