Formaldehyde condensation with glycine

The condensation of formaldehyde with glycine or glycine Schiff bases coordinated to Co", Cu and Ni" has been shown to give a-hydroxymethylserine. With [Cu(GlyO)2] the reaction of formaldehyde at the a-carbon is preceded by condensation on the amino group and is followed by cyclization to give an oxazolidine-type ring. 

The enzyme has also been used in the production of several natural amino acids such as L-serine from glycine and formaldehyde and L-tryptophan from glycine, formaldehyde, and indole [77-79], In addition, SHMT has also been used for the production of a precursor, 20, to the artificial sweetener aspartame (21) through a non-phenylalanine-requiring route (Scheme 14) [80-83]. Glycine methyl ester (22) is condensed with benzaldehyde under kinetically controlled conditions to form L-enY/ ra-p-phenylserine (23). This is then coupled enzymatically using thermolysin with Z-aspartic acid (24) to form A -carbobcnzyloxy-L-a-aspartyl-L-eryt/zro-p-phenylserine (20). and affords aspartame upon catalytic hydrogenation. 

P-Hydroxy-a-amino Acids. Another reaction of glycine is catalyzed by pyridoxal. This is the reversible condensation with aldehydes. Glycine and formaldehyde form serine in a model of the reaction observed in biological systems to proceed with tetrahydrofolic acid as a formaldehyde acceptor and donor. When glyoxylate reacts with pyridoxamine, the gly-... 

When glycine is heated with pyridoxal and alum between pH 4 and 6 an insoluble material is formed. The yellow material contains two equivalents of pyridoxal per aluminum, but only one of these is active as a growth factor for yeast the other was found as a condensation product with glycine, liberated by acid from the original complex and identified as S-pyridoxylserine. This is analogous to serine formed from formaldehyde and glycine, with the aldehyde of pyridoxal becoming the jS-carbon of serine. The proposed structure for the complex is shown in (I). 

Side chain cleavage (Group c). In a third type of reaction the side chain of the Schiff base of Fig. 14-5 undergoes aldol cleavage. Conversely, a side chain can be added by (3 condensation. The best known enzyme of this group is serine hydroxymethyltransferase, which converts serine to glycine and formaldehyde.211-21313 The latter is not released in a free form but is transferred by the same enzyme specifically to tetrahydrofolic acid (Eq. 14-30), with which it forms a cyclic adduct. 

When applied to formaldehyde, however, the reaction is somewhat anomalous in that methyleneaminoacetonitrile (CH2=N CH2-CN), the condensation product derived from the aldehyde and the amino nitrile, is formed (Expt 5.181). The free amino nitrile is obtained by careful basification of its sulphate salt, which is formed when methyleneaminoacetonitrile is treated with concentrated sulphuric acid in ethanol. Details of the hydrolysis of the amino nitrile (as the sulphate) under basic conditions are given. Barium hydroxide is used, the excess of which is finally removed by precipitation as the sulphate to facilitate the isolation of the glycine formed. 

The indole alkaloids provide an even richer source of biogenetic interrelationships. Thus, condensation of tryptamine and dihydroxyphenyl-acetadehyde (or equivalent precursors) under conditions similar to those already described gives a tetrahydro-harman derivative (diagram 26 cf. 336,338). Further condensation of this with formaldehyde (cf. 335) (which may be biogenetically derived from, say, serine or glycine) gives the same basic skeleton as in the alkaloid yohimbine. 

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