Synthesis from glycine

As a result of the principal importance of a-amino acids, their synthesis from glycine or other a-amino acids by a-alkylation of a derivative with a nonracemic auxiliary has been carried out more or less successfully127. Attempts aiming at the same goal, but using heterocyclic starting materials, are described in Sections 1.1.1.3.3.4.2. and 1.1.1.3.3,4.3. 2-Hydroxypinan-3-one (5) was used to induce chirality, when its imines with a-amino acids were a-alkylated,28 l3°. 

A. The amount of creatine in liver cells determines its rate of synthesis from glycine, arginine, and SAM. In muscle, creatine is converted to creatine phosphate, which is nonenzymati-cally cyclized to form creatinine. The amount of creatinine excreted by the kidneys each day depends on body muscle mass. In kidney failure, the excretion of creatinine into the urine will be low. 

This diketopiperazine could arise both from glycyl-d-alanine and d-alanyl-glycine by the above method. It could also arise by synthesis from glycine and d-alanine under the conditions of the experiment control experiments were carried out to determine this possibility, and they showed that this was impossible so that there was no doubt concerning the presence of a dipeptide amongst the products of hydrolysis. Since this dipeptide was resistant to trypsin it was most probably glycyl-d-alanine and not d-alanyl-glycine which is easily hydrolysed by this enzyme. 

In all reactions, the first stage is formation of SchifTs base a by condensation of PalP and the amino acid. Schiff s bases a and b represent part of transamination, but for the complete mechanism see Transamination. Racemization a- b, followed by b-ia-iamino acid-1-PalP, with addition of the proton in the opposite configuration. Amino acid decarboxylation a -> d- c - amine + PalP. Serine hydroxymethyltransferase (EC 2.1.2.1) X = OH L-serine + PalP a f- g glycine + PalP reversal of these reactions leads to L-serine synthesis from glycine the hydroxymethyl group is carried by te-trahydrofolic acid. Cysteine desulfhydrase (EC 4.4.1.1) X = SH cy eine + PalP a b-> c-y hydro-... 

When a comparison was made of inosinic acid synthesis from glycine-1-C and HC OOH in the presence of added nonlabeled inosinic acid, it was observed that radioactive formate was incorporated into the acid far in excess of that anticipated from the amount of glycine utilized.i " For example, instead of a 2 1 molecular utilization of the formate glycine... 

With gently hemolyzed chicken erythrocytes PROTO synthesis from glycine is markedly depressed but may be restored partially by the addition of various cofactors (35). For example, 80% of the activity may be restored by the addition of glycine, pyridoxal-P, and an acid-deproteinized pig liver fraction the synthesis may then continue over a period of 15 hr. 

The substance represented by formula (IV), viz., 4-hydroxy-3-allyl-3 4-dihydroqviinazoline, m.p. 130°, was synthesised by Reynolds and Robinson, and proved to be different from vasicine. Spath and Kuffner established the identity of the degradation product (V), upon which formula (IV) for vasicine was chiefly based by synthesis from isatoic anhydride, which, on treatment with glycine ester hydrochloride and sodium meth-oxide, gave the substituted Wppuric acid (VI), and this, on heating with... 

Exposure of compound 16, a substance that can be obtained in a straightforward manner from glycine, to sodium tert-butoxide furnishes an enolate that undergoes conversion to 8 upon treatment with terf-butyl formate. It was anticipated that the phthalimido and tert-butyl ester protecting groups in 8 could be removed easily and selectively under anhydrous conditions at a later stage in the synthesis. 

These mechanisms for the synthesis of glycine present a partial barrier to the movement of FA carbons into this molecule, the most abimdant AA in collagen. On the other hand, proline is synthesized from a-keto glutarate which can be freely derived from either carbohydrates or FAs thus the synthesis of pro line does not present a barrier to entry ofFA-derived carbons into collagen. 

Researchers at the University of Graz, in collaboration with scientists from DSM, have developed an elegant and novel approach to the synthesis of P-amino alcohols using two different enzymes in one pot (Scheme 2.35). For example, a threonine aldolase-catalyzed reaction was initially used, under reversible conditions, to prepare L-70 from glycine 69 and benzaldehyde 68. L-70 was then converted to (R)-71 by an irreversible decarboxylation catalyzed by L-tyrosine decarboxylase. In a second example, D/L-syn-70 was converted to (R)-71 using the two enzymes shown combined with a D-threonine aldolase in greater than 99% e. e. and 67% yield ]37, 38]. 

ALA and PBG are the precursors of porphyrin synthesis (Fig. 7.3.1). ALA is synthesized from glycine and succinyl-coenzyme A by ALAS. Two molecules of ALA are converted to PBG by the enzyme ALAD. 

FIGURE 18-14 Treatment for deficiencies in urea cycle enzymes. The aromatic acids benzoate and phenylbutyrate, administered in the diet, are metabolized and combine with glycine and glutamine, respectively. The products are excreted in the urine. Subsequent synthesis of glycine and glutamine to replenish the pool of these intermediates removes ammonia from the bloodstream. 

Another synthesis of pyrrolidines, in this case with high enantioselectivity, has seen several enones with a chiral alkoxy or amino substituent in the y-position react with azome-thine yields (derived from glycine imine derivatives) upon treatment with DBU/AgOAc (equation 171)612-614. This reaction may also be done using other alkene-containing substrates615,616. 

Amino acid synthesis (8, 389). Alkylation of the aldimine (1) from glycine ethyl ester and /j-chlorobenzaldehyde under phase-transfer conditions offers a general route to amino acids. Either liquid-liquid phase-transfer or solid-liquid phase-transfer catalytic conditions are satisfactory with active halides, but alkylation with allylic halides and less active alkyl halides is best effected under ion-pair extraction conditions (6,41), with 1 equiv. of tetra-n-butylammonium hydrogen sulfate (76-95% yields).1... 

Since the aldimine Schiff base 21 can be readily prepared from glycine, direct stereoselective introduction of two different side chains to 21 by appropriate chiral phase-transfer catalysis would provide an attractive, yet powerful, strategy for the asymmetric synthesis of structurally diverse a,a-dialkyl-a-amino acids. This possibility of a one-pot asymmetric double alkylation has been realized by using N-spiro chiral quaternary ammonium bromide le (Scheme 5.21). 

While the experiments of Fig. 3 were performed with glycine, other peptides have been synthesized from other amino acids such as lysine, phenylalanine or proline 27 28). Peptide synthesis from an eighteen amino acid mixture has been also demonstrated by using (histidine and lysine)-rich proteinoid. When the product is fractionated on Sephadex G-25, most of the oligopeptides appear to be in the dipeptide-tripeptide range or larger, and little of free amino acids survive from the reaction. Virtually all types of amino acid appear to yield peptides (Fig. 4) 29). 

Synthesis of peptides from amino acids in the solid state or in aqueous solution has been reported with the aid of ATP, Mg2 and free imidazole 34 36). a 4.5 % yield of glycine peptides has been reported in the solid state, 0.6 % yield in aqueous solution 36). Gly-N-pA is formed in a yield of 72.5 % from glycine and chemically synthesized ImpA in aqueous solution, pH 8.0, at room temperature 37). At initial of pH 6.0 glycyl 5 -adenylate (gly-O-pA) and 2 (3 )-0-glycyl adenosine 5 -phosphate (pA-g W are formed 37). 

In an extension of the work on the synthesis of IV-substituted amino sugars by the amino nitrile method, Kuhn and coworkers13 have prepared 2-(carboxymethylamino)-2-deoxy-D-glucose (2-deoxy-2-glycino-D-glucose), as the dipolar ion LXXXII, from glycine ethyl ester plus D-arabinose. 

Fig. 2. Pathway of the synthesis of heme and chlorophyll, (a) Synthesis of porphobilinogen from glycine and succlnyl CoA (b) synthesis of protoporphyrin IX from porphobilinogen. A = CH2COOH, M = CH3, P = CH2CH2COOH.

Protein synthesis Glycogen synthesis Lactate uptake Amino acid uptake Glutaminase Glycine oxidation Ketoisocaproate oxidation Acetyl-CoA carboxylase Urea synthesis from amino acids Glutathione (GSH) efflux Taurocholate excretion into bile Actin polymerization Microtubule stability Lysosomal pH... 

This process could also be applied to the synthesis of tripeptides. A Cbz-protected dipeptide (Cbz-Ala-Gly-OEt) was deprotected in flow using the H-Cube system, and using the above procedure the tripeptide Cbz-Phe-Ala-Gly-OEt was obtained in 59% overall yield and in only 6-7 h, based on the longest linear sequence from glycine. 

Palamidessi and Bernardi have obtained 2-chloropyrazine 1-oxide by mild treatment of pyrazine 1,4-dioxide with phosphoryl chloride. The structure of the 1-oxide was confirmed by hydrolysis to 2-hydroxy-pyrazine 1-oxide, which was also prepared by direct synthesis from glyoxal and glycine hydroxamic acid.398 This synthesis is illustrative of a general method for preparing 2-hydroxypyrazine 1-oxides by condensation of a,/3-dicarbonyl compounds with a-aminohydroxamic acids. An analogous synthesis of 2-aminopyrazine 1-oxides has already... 

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