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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.16, #3-4)

Enzymatic resolution of amino acids via ester hydrolysis by Prof. T. Miyazawa D.Sc. (pp. 191-213).

The present review outlines recent examples of enzyme-based resolution procedures for amino acids via the hydrolysis of their esters. The resolutions have been achieved by using proteases (α-chymotrypsin, subtilisin and other microbial proteases, and sulfhydryl proteases of plant origin) and lipases. Relevant work utilizing yeast and other microbial cells is also included.

Keywords: Amino acids; Enzymatic resolution; Ester hydrolysis; Proteases; Lipases

How to build optically activeα-amino acids by Dr. M. Calmes; J. Daunis (pp. 215-250).

Various methodologies published in the literature dealing withα-amino carboxylic acid asymmetric synthesis are presented in a digest form. In each case, only some recent or most typical works are mentioned.

Keywords: α-Amino acid; Asymmetric synthesis; Chiral reagent; Asymmetric auxiliary

Syntheses of optically active 2-amino-4-oxobutyric acid and N,O-protected derivatives by Dr. Patrick R. Meffre (pp. 251-272).

Strategies for the synthesis of optically active aspartaldehyde derivatives are reviewed. Most of them are using the chiral pool: allylglycine or naturally occurring homoserine, aspartic acid or methionme and side chain modifications. This will be developed in the first part. Some other original routes are also displayed in the second part. Different aspects of each strategy are discussed: the nature and number of steps, the problem of protecting groups, the price and availability of starting materials. Some synthetic applications of such interesting chiral synthons are shown in the last part.

Keywords: Amino acids; Unusual amino acids; Aspartic acidβ-semialdehyde; Aspartaldehyde; 2-Amino-4-oxobutyric acid; Enantioselective synthesis

Synthesis of optically active lipidicα-amino acids and lipidic 2-amino alcohols by V. Constantinou-Kokotou; Assoc. Prof. George Kokotos (pp. 273-285).

Lipidicα-amino acids (LAAs) are a class of compounds combining structural features of amino acids with those of fatty acids. They are non-naturalα-amino acids with saturated or unsaturated long aliphatic side chains. Synthetic approaches to optically active LAAs and lipidic 2-amino alcohols (LAALs) are summarized in this review. A general approach to enantioselective synthesis of saturated LAAs is based on the oxidative cleavage of 3-amino -1,2-diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols. Unsaturated LAAs are prepared in their enantiomeric forms by Wittig reactionvia methyl (S)-2di-tert-butoxycarbonylamino-5-oxo-pentanoate. This key intermediate aldehyde is obtained by selective reduction of dimethyl N,N-di-Boc glutamate with DIBAL. (R) or (S) LAALs may be prepared starting from D-mannitol or L-serine. LAAs are converted into LAALs by chemoselective reduction of their fluorides using sodium borohydride with retention of optical purity. Replacement of the hydroxyl group of LAALs by the azido group, followed by selective reduction leads to unsaturated optically active lipidic 1,2-diamines.

Keywords: Lipidicα-amino acids; Lipidic amino alcohols; Lipidic diamines; Enantioselective synthesis; Enantiomeric excess; Wittig reaction; Glutamic acid semialdehyde

A new protection/activation strategy for the synthesis of naturally occurring and non-naturalα-N-alkylamino acids by Prof. Dr. Klaus Burger; H. Sehedel; J. Spengler (pp. 287-295).

A new method for the preparation of N-methylamino acids and some of their derivatives starting from hexafluoroacetone protected amino acids is described. The new concept results in saving of steps compared to conventional protection/activation techniques. Protection and deprotection proceed without racemization.

Keywords: Amino acids; Hexafluoroacetone; α-N-Methylamino acids; α-N-Phosphinoylmethylamino acids; Pro-Glu-chimeras; Pro-Tauchimeras

Asymmetric syntheses of pipecolic acid and derivatives by Dr. François Couty (pp. 297-320).

Results in the field of asymmetric synthesis of pipecolic acid derivatives are reviewed. Three sections describe the asymmetric syntheses of the title compounds (i) from the chiral pool (α-amino acids or carbohydrates) (ii) using a chiral auxiliary either derived from terpenes,α-amino acids, tartaric acid, an amine orβ-amino alcohols (iii) by means of asymmetric catalysis.

Keywords: Amino acids; Pipecolic acid; Pipecolic acid derivatives; Asymmetric synthesis; Hemisyntheses; Chiral auxiliaries

Fromβ-lactams toα- andβ-amino acid derived peptides by Dr. Claudio Palomo; J. M. Aizpurua; I. Ganboa; M. Oiarbide (pp. 321-343).

The potential ofβ-lactams as intermediates for the access toα- andβ-amino acid-derived peptides is shortly reviewed, with major focus on the technologies developed in our group. The two general strategies lie, on one side, in the oxidative ring expansion of 3-hydroxyβ-lactams toN-carboxyα-amino acid anhydrides or Leuch's anhydrides and subsequent coupling withα-amino acid esters and, on the other side, in the nucleophilic ring opening ofN-Boc-β-lactams. Both approaches have been successfully applied to the synthesis ofα,β-diamino acid,α-amino-β-hydroxy acid, polyhydroxylatedα-amino acid,α,α-disubstitutedα-amino acid,β-amino acid,β-amino-α-hydroxy acid andβ,β-disubstitutedβ-amino acid derived peptides. Because of the mild reaction conditions needed for the above transformations and the highly stereoselective procedures employed for the construction of the startingβ-lactam ring, the whole process allows the production of optically pure final products.

Keywords: Amino acids; Amino alcohols; β-Lactams; NCA; Peptides; Synthesis

Some of the amino acid chemistry going on in the Laboratory of Amino Acids, Peptides and Proteins by S. Bouifraden; C. Drouot; M. El Hadrami; F. Guenoun; L. Lecointe; N. Mai; M. Paris; C. Pothion; M. Sadoune; B. Sauvagnat; M. Amblard; J. L. Aubagnac; M. Calmes; P. Chevallet; J. Daunis; C. Enjalbal; J. A. Fehrentz; F. Lamaty; J. P. Lavergne; R. Lazaro; V. Rolland; M. L. Roumestant; Ph. Viallefont; Y. Vidal; Dr. J. Martinez (pp. 345-379).

Some of the chemistry of amino acids going on in our laboratory (Laboratoire des Amino acides Peptides et Protéines) is described as well as some mass spectrometry methodology for their characterization particularly on solid supports. Several aspects are presented including: (i) the stereoselective synthesis of natural and unnatural amino acids using 2-hydroxypinan-3-one as chiral auxiliary; (ii) the stereoselective synthesis of natural and unnatural amino acids by deracemization ofα-amino acidsvia their ketene derivatives; (iii) the synthesis ofα-aryl-α-amino acidsvia reaction of organometallics with a glycine cation; (iv) the diastereoselective synthesis of glycosyl-α-amino acids; (v) the synthesis ofβ-amino acids using a-aminopyrrolidinopiperazinediones as chiral templates; (vi) the reactivity of urethane-N-protected N-carboxyanhydrides. To characterize natural and non natural amino acids through their immonium ions by mass spectrometry, some methodology is also described.

Keywords: α-Amino acids; β-Amino acids; α-Aryl-α-amino acids; Chiral auxiliary; Deracemization; Glycosyl-α-amino acids; 2-Hydroxypinan-3-one; Immonium ions; Urethane N-protected N-carboxyanhydrides

Synthesis of perfluoroalkylatedβ-alanine and some peptide derivatives: An access to original surfactants by M. S. Özer; C. Gérardin-Charbonnier; S. Thiébaut; L. Rodehüser; Professor C. Selve (pp. 381-389).

The reaction of amines or sodium azide with 3-perfluoroalkyl-3-fluoroprop-2-enoate, followed by hydrogenation, affords perfluoroalkylatedβ-alanine analogues in very good yields. These compounds can be linked via an amide bond to produce peptide analogues such as carnosine or carcinine derivatives, which could have surfactive and complexing properties.

Keywords: Amino acids; Perfluorinated compounds; Surfactants; Complexing properties; Carnosine; β ; Amino acids; Blood substitutes

Asymmetric hydrogenation of dehydrodipeptide esters bearing different protective groups by Dr. Chr Döbler; H. -J. Kreuzfeld; Chr Fischer; M. Michalik (pp. 391-401).

N-[(Z)-N-Benzoyl- orN-Boc-(2-fluorophenyl)dehydroalanyl]-(R)-or (S)-phenylalanine esters were synthesized and hydrogenated to give the corresponding dipeptide derivatives with optical yields in the range of 53–87%de using the cationic rhodium complexes of PROPRAPHOS and BPPM. The efficiency of chiral diphosphine ligands as well the effect of the chiral center in the substrate on the catalytic asymmetric induction was studied.

Keywords: Amino acids; Dipeptide derivatives; Non-proternogenic optically active dipeptide esters; Dehydrodipeptides; Chiral rhodium catalysts; Asymmetric hydrogenation; Diastereoselectivity

Spectral analysis of a series of partially protected and deprotected tetrapeptides, analogues of AS-I phytotoxin by V. Magafa; Dr. G. Stavropoulos; A. Aaberg; M. Liakopoulou-Kyriakides (pp. 403-413).

A series of six tetrapeptides, analogues of AS-I phytotoxin, pathogenic to sunflower, have been synthesized either in solution and/or by solid phase methods and have been tested for phytotoxic activity in various plants and cytotoxic activity in three cancer cell lines. These peptides were identified as model compounds by fast atom bombardment (FAB), plasma desorption (PD), electrospray ionization (ESI) mass spectrometry and by¹H,¹H-¹H,¹³C and¹H-¹³C NMR. The data presented show that in protected tetrapeptides the molecular ion was easily identified whereas some difficulties appeared with the fully deprotected peptides. NMR spectra are given.

Keywords: Amino acids; Phytotoxin AS-I analogues; FAB; PD; ESI mass spectrometry; ¹H,¹³C and 2D NMR

Cu(III)-Polypeptide complexes exhibiting SOD-like activity by M. Liakopoulou-Kyriakides; S. Hadjispyrou; A. Zarkadis (pp. 415-423).

The SOD-like activity of Cu(III) -complexes with polypeptides poly-L-lysine and poly-L-glutamic acid respectively was investigated. The Cu(II)-polypeptide complexes were first oxidized by K₂IrCl₆ to give the corresponding Cu(III) -compounds.The oxidation of Cu(II) and the corresponding Cu(II)/Cu(III) potential was evaluated by cyclic voltammetry (c.v.), UV-Vis and EPR spectroscopic (r.t.) experiments. Spin trapping EPR spectra were also conducted to confirm the formation of the superoxide radical. The SOD-like activity of each Cu(III)-complex was proved using the nitro blue tetrazolium (NBT) method slightly modified.

Keywords: Amino acids; SOD-like activity; Cu (III)-Poly-L-lysine; Cu(III)-Poly-L-glutamic acid

Synthesis and anti-phlogistic potency of some new non-proteinogenic amino acid conjugates of “Diclofenac” by Dr. M. H. Abo-Ghalia; A. M. Shalaby; W. I. El-Eraqi; H. M. Awad (pp. 425-440).

In search for more potent, particularly less ulcerogenic gastritis that hopefully replace the universal NSAID “Diclofenac”, (2-[(2,6-di-chlorophenyl)amino]-phenylacetic acid, C.A.S. 15307-86-5), twelve new non-proteinogenic amino acid conjugates of the drug, namely that of sarcosine,β-alanine, D-leucine and D-phenylalanine, were synthesized and biologically screened for their anti-inflammatory, analgesic and ulcerogenic activity in rats.“Diclofenac” amino acid esters (IIa-d), were synthesizedvia the corresponding HOSu or HOBt active esters. Alkaline hydrolysis (NaOH) followed by acidification (KHSO₄) or thioamide formation (Lawsson's Reagent, C.A.S. 19172-47-5), afforded the corresponding free acids IIIa-d or the thioamides IVa-d respectively.Interestingly, in contrary to the parent “Diclofenac”, the synthesized candidates (except IIId), were entirly nonulcerogenic in rats. Further, they considerably retained a generelized anti-phlogistic activity. The major “Diclofenac” irritating gastric side effect was thus eliminated.Particularly, the sarcosine conjugate IIa and its thiomimic IVa exhibit promising therapeutic perspectives.

Keywords: Amino acids; Diclofenac; Anti-phlogistics; Non-proteinogenic amino acids; Voltaren®. Thionation; Cyclo-oxygenase inhibitors; Ulcerogenic gastritis

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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.16, #3-4)

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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.16, #3-4)