Amino-acids

BY J. H. JONES

In one way or another, the whole of this Report is about the chemistry of amino-acid derivatives, but here we are concerned only with the amino–acids themselves. Emphasis is on α-amino-acids, and it is only for these that comprehensive coverage has been attempted. Furthermore, although many may think it retrogressive to draw demarcation lines between disciplines in these enlightened times, amino-acid biochemistry has been excluded. Amino-acid chemistry is under continuous scrutiny from every conceivable angle, and so papers on these compounds span a very diverse range of interests. The Reporter therefore makes no apology for the fact that this chapter is something of a miscellany.

1 Naturally Occurring Amino-acids

A. Occurrence of Known Amino-acids. — Pipecolic acid (of unstated configuration, but presumably L) has been isolated from azuki beans (Phaseolus angularis) in a yield of about 0.05%. N-Methyl-L-alanine, which has not been found in higher plants before, has been isolated from the leaves of Dichapetalum cymosum. This plant is toxic and causes considerable cattle loss in southern Africa because it produces fluoroacetate. Young leaves contain remarkably large amounts of N-methyl-L-alanine (up to 5.6% by weight on a dry-weight basis) and it was suggested that the metabolism of the amino-acid and the toxin might be linked. Erythro-γ-methyl-L-glutamic acid has been isolated from seeds of Lathyrus maritimus and distinguished from the other possible methylglutamic acids by nuclear magnetic resonance (n.m.r.) spectrometry: chromatographic evidence indicates that this amino-acid also occurs in other Lathyrus species. Nε-Trimethyl-L-lysine has been isolated from seeds of Reseda luteola and from chicken erythrocyte histones, where it occurs together with Nε-methyl- and Nε-dimethyl-L–lysine.6-Hydroxykynurenic acid has been obtained from tobacco leaves, thus providing the first example of the occurrence of a kynurenic acid derivative in plants. A survey of the distribution of fifteen non-protein amino-acids in about forty species of the genus Acacia shows that members of the Gummiferae series can be distinguished by their amino-acid content: they alone contain N-acetyldjenkolic acid, and they lack several amino-acids which are widely distributed among other Acacia species. The possibility that the toxicity of various species of Crotalaria may not be due solely to the presence of pyrrolizidine alkaloids in these plants has been demonstrated by the isolation of the neurotoxin α-amino-β-oxalylaminopropionic acid from seeds of C. incana and C. mucronata. Trans -3-hydroxy-L-proline has been isolated from seeds and vegetative tissue of Delonix regia, where it is a major component of the free amino-acid pool.

B. New Naturally Occurring Amino-acids. — A number of new natural amino-acids have been characterised during the year: these are listed at the end of this section, together with their sources. Those whose structure has been confirmed by synthesis are included in the list of newly synthesised amino-acids in section 2. The increasing usefulness of physical methods for the characterisation of amino-acids is apparent: n.m.r. and mass spectrometry (applications of mass spectrometry in amino-acid and peptide chemistry have been reviewed) have been particularly valuable. Especially noteworthy is the characterisation of the novel amino-acid (1) by spectroscopic methods.

C. A List of New Naturally Occurring Amino-acids. —

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2 Chemical Synthesis and Resolution of Amino-acids

The majority of new syntheses reported this year were performed by variations of well-established routes or involved elaboration of available amino-acids. Therefore, only those syntheses which have points of particular interest will be discussed in the following outline, the remainder being merely mentioned or incorporated into the appendix to this section (see p. 13).

A. Protein Amino-acids. — New syntheses have been reported for DL–lysine, DL-histidine, DL-cystine, and DL-tryptophan, and reactions for the conversion of serine to DL-cystine, L-tyrosine to L-phenylalanine, and L-ornithine to L-proline have been described. The resolution of racemic glutamic acid and alanine by preferential crystallisation has been studied in detail by Japanese workers.

B. Other α-Amino-acids. — A very brief preliminary description of a new general route to α-amino-acids has appeared: treatment of an NN-bis(trimethylsilyl)glycine ester (2) with base followed by reaction with an alkyl halide results in alkylation of the α-carbon atom giving (3) which is very easily hydrolysed to an α-amino-ester with dilute acid.

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A convenient synthesis of DL-α-aminosuberic acid (by the diethyl acetamidomalonate route) has been reported: resolution can be achieved enzymically or, preferably, by the method of Vogler et al. using optically active tyrosine hydrazide. An improved method for the conversion of tyrosine (D and L) to 3,5-dichlorotyrosine has been described. Synthesis of α,α-diaminopimelic acid by the method of Work et al. gives an equimolecular mixture of racemic and meso diaminodiacids: a simpler method for separating the isomers and resolving the racemate has been published. DL-α-Acetamido-β-methylaminopropionic acid has been obtained by an improved procedure. Stereospecific enzymic deacylation gave L-α-amino-β-methylaminopropionic acid which had the same specific rotation as a sample of the same amino-acid isolated in 1967 from Cycas circinalis, thus confirming the L configuration of the latter.

L-Felinine (4) can be prepared by acid-catalysed S-alkylation of L-cysteine with 2-methylbut-1-ene-4-ol or 2-methylbut-2-ene-4-ol.

Birch reduction of phenylalanine gives 3,6-dihydrophenylalanine (5), which can be partially hydrogenated to 3,4,5,6-tetrahydrophenylalanine (6). The position of the double bond in (6) was confirmed by isolation of the lactone (7) after treatment with hydrochloric acid, and hydrolysis of (7) gave the new amino-acid (8).

Allenic aldehydes such as (9) which are fully substituted at the 2-position give good yields in the Strecker synthesis, but poor yields of allenic amino–acids are obtained if this position is unsubstituted. The reaction of allenic bromides with diethyl formamidomalonate is a more general route to such amino-acids: the reaction is applicable to...