Skip to main content
SpringerLink
Log in

β,γ-Alkynylα-amino acids: a synthetic challenge

  • Review Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Summary

Ethynyl glycine is a naturally occurring unusualα-amino acid. Its known chemical and biological properties are summarized in the first part of this review. The second part is an overview on racemic syntheses of ethynyl glycine and otherβ,γ-alkynylα-amino acid derivatives, including patent data. These small polyfunctional compounds revealed as being very labile and the synthesis of mainly fully or partially protected forms seemed to have been actually performed. The last part deals with the approaches to the enantioselective synthesis ofβ,γ-alkynylα-amino acids derivatives, and details the only satisfactory strategy that has led to optically activeβ,γ-alkynylα-amino acids derivatives up to now.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abdulganeeva SA, Erzhanov KB (1991) Acetylenic amino acids. Russ Chem Rev 60: 676–688

    Google Scholar 

  • Abeles RH, Maycock AL (1976) Suicide enzyme inactivators. Acc Chem Res 9: 313–319

    Google Scholar 

  • Abeles RH (1980) Suicide enzyme inactivators and others. Pure Appl Chem 53: 149–160

    Google Scholar 

  • Abeles RH (1983) Suicide enzyme inactivators. Chem Eng News 61: 48–56

    Google Scholar 

  • Agouridas C, Tessot N, Martel A (1990) Nouveaux dérivés insaturés de l'acide 2,6-amino heptanedioique, leur procédé de préparation et leur application comme médicaments. Eur P 0394118

  • Angst C (1987) Stereoselective synthesis ofβ,γ-unsaturated amino acids. Pure Appl Chem 59: 373–380

    Google Scholar 

  • Beaulieu PL, Duceppe JS, Johnson C (1991) Synthesis of chiral vinyl glycines. J Org Chem 56: 4196–4204

    Google Scholar 

  • Bey P (1989) Mechanism-based inhibitors: fifteen years later. XXIVèmes rencontres internationales de chimie thérapeutique (1988) Strasbourg, France. Société de chimie thérapeutique Pub. 16ème série, pp 111–122

  • Bijoy P, Subba-Rao GSR (1993) An unusual C-C bond cleavage with chromium-VI reagents: oxidation of primary alcohols to ketones. Synth Commun 23: 2701–2708

    Google Scholar 

  • Bowlin TL (1992) 5-Amine substituted adenosine analogs as immunosuppressants. Eur P 0472181

  • Branquet E, Durand P, Vo-Quang L, Le Goffic F (1993) A straightforward synthesis of N-tert-butoxycarbonyl serinate acetonide methyl ester. Synth Commun 23: 153–156

    Google Scholar 

  • Cainelli G, Cardillo G (1984) Chromium oxidation in organic synthesis. Springer, Berlin Heidelberg New York Tokyo, pp 118–151, pp 204–216

    Google Scholar 

  • Casara P, Danzin C (1990) S-adenosylmethionine decarboxylase inhibitors. Eur P 0351475

  • Casara P, Metcalf B (1978) Trimethylsilylacetylene-N-carboethoxy glycinate dianion — a general synthon forα-acetylenicα-amino acids. Tetrahedron Lett: 1581–1584

  • Casara PJ, Jung M, Metcalf BW (1978) Lower alkyl 2-tri-(lower)alkylsilylacetylene-N-carbethoxyglycinates and process for using same. US P 4088667

  • Castelhano AL, Horne S, Taylor GJ, Billedeau R, Krantz A (1988) Synthesis ofα-amino acids withβ,γ-unsaturated side chains. Tetrahedron 44: 5451–5466

    Google Scholar 

  • Colson PJ, Hegedus LS (1993) Asymmetric synthesis ofα-alkyl-α-amino acids from chromium-carbene-complex-derivedβ-lactams. J Org Chem 58: 5918–5924

    Google Scholar 

  • Danzin C, Casara P, Claverie N, Metcalf BW (1981)α-Ethynyl andα-vinyl analogues of ornithine as enzyme-activated inhibitors of mammalian ornithine decarboxylase. J Med Chem 24: 16–20

    Google Scholar 

  • Duthaler RO (1991) Synthesis ofβ,γ-unsaturated D-α-amino acids from L-cysteine. Angew Chem Int Ed Engl 30: 705–707

    Google Scholar 

  • Duthaler RO (1992) Partialsynthese von ungewöhnlichen Aminosäuren aus Serin oder Cystein. GIT Fachz Lab 36: 479–488

    Google Scholar 

  • Duthaler RO (1994) Recent developments in the stereoselective synthesis ofα-amino acids. Tetrahedron 50: 1539–1650

    Google Scholar 

  • Duthaler RO, Hafner A (1994) New tools for stereoselective synthesis: A.(L)-cystein as (D)-amino acid synthon. B. Chiral titanium reagents. In: Makriyannis A, Castagnoli N (eds) Proceedings of the 5th Cyprus conference on new methods in drug design (1992). JR Prous Science Publishers SA

  • Garner P (1984) Stereocontrolled addition to a penaldic acid equivalent: an asymmetric synthesis ofthreo-β-hydroxy-L-glutamic acid. Tetrahedron Lett 25: 5855–5858

    Google Scholar 

  • Garner P, Park JM (1987) The synthesis and configurational stability of differentially protectedβ-hydroxy-α-amino aldehyde. J Org Chem 52: 2361–2364

    Google Scholar 

  • Garner P, Park JM (1992) 1,1-dimethyl (S)- or (R)-4-formyl-2,2-dimethyl-3-oxazolidine carboxylate: a useful serinal derivative. Org Synth 70: 18–28

    Google Scholar 

  • Haines AH (1985) Best synthetic methods: methods for the oxidation of organic compounds: alkanes, alkenes, alkynes and arenes. Academic Press, London, pp 153–172

    Google Scholar 

  • Haines AH (1988) Best synthetic methods: methods for the oxidation of organic compounds: alcohols, alcohols derivatives, alkyl halides, nitroalkanes, alkyl azides, carbonyl compounds, hydroxyarenes and aminoarenes. Academic Press, London, pp 148–165

    Google Scholar 

  • Havlicek L, Hanus J (1991) Syntheses ofβ,γ-unsaturatedα-amino acids. Collect Czech Chem Commun 56: 1365–1399

    Google Scholar 

  • Holland BC, Gilman NW (1974) An improved procedure for the oxidation of alkynols to alkynoic acids. Synth Commun 4: 203–210

    Google Scholar 

  • John RA (1980) Enzyme inhibitors as drugs: enzyme-induced inactivation of pyridoxal phosphate-dependent enzymes: approaches to the design of specific inhibitors. In: Sandler M (ed) Macmillan Press ltd, London Basingstoke, pp 73–93

    Google Scholar 

  • Jung MJ (1985) Chemistry and biochemistry of the amino acids. In: Barret GC (ed) Chapman and Hall, London New York, pp 227–245

    Google Scholar 

  • Jung MJ, Palfreyman MG, Ribereau-Gayon G, Bey P, Metcalf BW, Koch-Weser J, Sjoerdsma A (1979) Drug action and design: mechanism-based enzyme inhibitors: effects of enzyme-activated irreversible inhibitors of aromatic amino acids decarboxylase on endogenous synthesis of biogenic amines. In: Kalman T (ed) Proceedings of the twentieth annual medicinal chemistry symposium. Amherst, New York, USA, May 1979. Developments in biochemistry, vol 6. Elsevier/North-Holland, New York Amsterdam Oxford, pp 131–144

    Google Scholar 

  • Kuroda Y, Okuhara M, Goto T, Iguchi E, Kohsaka M, Aoki H, Imanaka H (1980a) FR-900130, a novel amino acid antibiotic I. discovery, taxonomy, isolation, and properties. J Antibiotics 33: 125–131

    Google Scholar 

  • Kuroda Y, Okuhara M, Goto T, Kohsaka M, Aoki H, Imanaka H (1980b) FR-900130, a novel amino acid antibiotic II. isolation and structure elucidaion of the acetyl derivative of FR-900130. J Antibiotics 33: 132–136

    Google Scholar 

  • Li M, Johnson ME (1995) Oxidation of certain 4-substituted phenethyl alcohols with collins reagents: on the mechanism of a carbon-carbon bond cleavage. Synth Commun 25: 533–537

    Google Scholar 

  • Manfré F, Kern JM, Biellman JF (1992) Syntheses of proline analogues as potential mechanism-based inhibitors of proline dehydrogenase: 4-methylene-L-, (E)- and (Z)-4-(fluoromethylene)-L-,cis- andtrans-5-ethynyl-(±)-, andcis- andtrans-5-vinyl-L-proline. J Org Chem 57: 2060–2065

    Google Scholar 

  • Maycock AL, Aster SD, Patchett AA (1979) Drug action and design: mechanism-based enzyme inhibitors: suicide inactivation of decarboxylases. In: Kalman T (ed) Proceedings of the twentieth annual medicinal chemistry symposium. Amherst, New York, USA, May 1979. Developments in biochemistry, vol 6. Elsevier/North-Holland, New York Amsterdam Oxford, pp 115–129

    Google Scholar 

  • Meffre P, Durand P, Branquet E, Le Goffic F (1994) A straightforward synthesis of N-Boc-L-serinal and N-Boc-L-threoninal acetonides. Synth Commun 24: 2147–2152

    Google Scholar 

  • Meffre P, Gauzy L, Perdigues C, Desanges-Levecque F, Branquet E, Durand P, Le Goffic F (1995) En route to optically active ethynyl glycine derivatives. Tetrahedron Lett 36: 877–880

    Google Scholar 

  • Meffre P, Gauzy L, Branquet E, Durand P, Le Goffic F (1996) Synthesis of optically activeβ,γ-alkynylglycine derivatives. Tetrahedron (in press)

  • Mehmandoust M, Petit Y, Larchevêque M (1992) Synthesis of (E)-β,γ-unsaturatedα-amino acids by rearrangement of allyltrichloroacetimidates. Tetrahedon Lett 33: 4313–4316

    Google Scholar 

  • Metcalf BW, Casara P (1979) Synthetic access toα-substituted prop-2-ynylamines andα-acetylenic amino acids via the t-butyl N-trimethylsilyprop-2-ynylcarbamate dianion. J Chem Soc Chem Comm: 119–120

  • Metcalf BW, Jung M (1979)α-Acetylenic derivatives ofα-amino acids. US P 4133964

  • Metcalf B, Sjoerdsma A (1979) Drug action and design: mechanism-based enzyme inhibitors: the microscopic reversibility principle in enzyme inhibition. In: Kalman T (ed) Proceedings of the twentieth annual medicinal chemistry symposium. Amherst, New York, USA, May 1979. Developments in biochemistry, vol 6. Elsevier/North-Holland, New York Amsterdam Oxford, pp 61–73

    Google Scholar 

  • Metcalf BW, Jung M (1980)α-Acetylenic derivatives ofα-amino acids. US P 4190586

  • Monroe RF, Lowes FJ, Foster GL, Oakes BD (1963) Propargyl compounds as corrosion inhibitors. US P 3079345

  • Mosher HS, Dale JA (1973) Nuclear magnetic resonance enantiomer reagents. Configurational correlationsvia nuclear magnetic resonance chemical shifts of diastereomeric mandelate, O-methylmandelate, andα-methoxy-α-trifluoromethylphenylacetate (MTPA) esters. J Amer Chem Soc 95: 512–519

    Google Scholar 

  • Nagata C, Yamaguchi T (1979) Molecular orbital study on the reaction mechanism of irreversible enzyme inhibitors. J Med Chem 22: 13–17

    Google Scholar 

  • Ohira S (1989) Methanolysis of dimethyl (1-diazo-2-oxopropyl)phosphonate: generation of dimethyl(diazomethyl)phosphonate and reaction with carbonyl compounds. Synth Commun 19: 561–564

    Google Scholar 

  • Rando RR (1974a)β,γ-Unsaturated amino acids as irreversible enzyme inhibitors. Nature 250: 586–587

    Google Scholar 

  • Rando RR (1974b) Chemistry and enzymology of kcat inhibitors. Science 185: 320–324

    Google Scholar 

  • Rando RR (1974c) Irreversible inhibition of aspartate aminotransferase by 2-amino-3-butenoic acid. Biochemistry 13: 3859–3863

    Google Scholar 

  • Rando RR (1975) Mechanisms of action of naturally occuring irreversible enzyme inhibitors. Acc Chem Res 8: 281–288

    Google Scholar 

  • Rando RR (1976) Mechanism of the irreversible inhibition of aspartate aminotransferase by the bacterial toxin L-2-amino-4-methoxy-trans-3-butenoic acid. J Biol Chem 251: 3306–3312

    Google Scholar 

  • Rando RR (1978) Enzyme-activated irreversible inhibitors: principles of catalytic enzyme inhibition. In: Seiler N, Jung MJ, Koch-Weser J (eds) Elsevier/North-Holland Biomedical Press, Amsterdam New York Oxford, pp 13–26

    Google Scholar 

  • Rando RR (1979) Drug action and design: mechanism-based enzyme inhibitors: natural and synthetic kcat-inhibitors of transaminases and decarboxylases. In: Kalman T (ed) Proceedings of the twentieth annual medicinal chemistry symposium. Amherst, New York, USA, May 1979. Developments in biochemistry, vol 6. Elsevier/North-Holland, New York Amsterdam Oxford, pp 47–60

    Google Scholar 

  • Rando RR (1984) Mechanism-based enzyme inactivators. Pharmacol Rev 84: 111–142

    Google Scholar 

  • Reginato G, Mordini A, Degl'Innocenti A, Caracciolo M (1995) Stereoselective synthesis of (R)-(−)-2,2-dimethyl-3-t-butoxycarbonyl-4-ethynyl-oxazolidine: a chiral building block for the synthesis of a new class of substituted alkynes. Tetrahedron Lett 36: 8275–8278

    Google Scholar 

  • Schöllkopf U, Westphalen KO, Schröder J, Horn K (1988) Studies on the acylation of lithiated bislactim ethers of cyclo(-L-Val-Ala-) and cyclo(-L-Val-Gly); asymmetric synthesis of (R)-α-alkenyl and (R)-α-ethinyl alanine methyl esters by the bislactim ether method. Liebigs Ann Chem 88: 781–786

    Google Scholar 

  • Sisido K, Hirowatari N, Tamura H, Kobata H, Takagisi H, Isida T (1970) Syntheses of all of the racemic diastereoisomers of phytosphingosine. J Org Chem 35: 350–353

    Google Scholar 

  • Stanley MS (1992) Orthogonally protected N-(carboxymethyl)-L-2,3-diaminopropanoic acids and O-(carboxymethyl)-L-serines for solid-phase peptide synthesis. J Org Chem 57: 6421–6430

    Google Scholar 

  • Stark GR, Bartlett PA (1983) Design and use of potent, specific enzyme inhibitors. Pharm Ther 23: 45–78

    Google Scholar 

  • Walsh C (1982) Suicide substrate: mechanism-based enzyme inactivators. Tetrahedron 38: 871–909

    Google Scholar 

  • Williams RM (1989) Synthesis of optically activeα-amino acids. Pergamon Press, Oxford

    Google Scholar 

  • Williams RM, Zhai W (1988) Versatile, strereocontrolled, asymmetric synthesis of Evinyl glycine derivatives. Tetrahedron 44: 5425–5430

    Google Scholar 

  • Williams RM, Aldous DJ, Aldous SC (1990a) General synthesis ofβ,γ-alkynylglycine derivatives. J Org Chem 55: 4657–4663

    Google Scholar 

  • Williams RM, Aldous DJ, Aldous SC (1990b) Synthesis of ethynyl glycine (FR-900130). J Chem Soc Perkin Trans I: 171–172

    Google Scholar 

  • Zhai D, Zhai W, Williams (1988) Alkynylation of mixed acetals with organotin acetylides. J Am Chem Soc 110: 2501–2505

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Bioorganique et Biotechnologies, associé au CNRS École Nationale Supérieure de Chimie de Paris, 11 rue P. et M. Curie, F-75231, Paris Cédex 05, France

    P. Meffre & F. Le Goffic

Authors
  1. P. Meffre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Le Goffic
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meffre, P., Le Goffic, F. β,γ-Alkynylα-amino acids: a synthetic challenge. Amino Acids 11, 313–328 (1996). https://doi.org/10.1007/BF00807939

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00807939

Keywords

Search

Navigation