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Amino Acids

, Volume 39, Issue 3, pp 849–858 | Cite as

A stereoselective synthesis of α-deuterium-labelled (S)-α-amino acids

  • Elaine O’Reilly
  • Daniele Balducci
  • Francesca Paradisi
Original Article

Abstract

An atom-efficient and stereoselective synthesis has been developed for the preparation of α-2H-labelled (S)-α-amino acids, starting from a novel chiral diketopiperazine scaffold. Efficient mono-alkylation of the chiral template afforded the (S)-substituted adducts with the nature of the electrophile significantly effecting the stereochemical outcome. Subsequent alkylation was totally selective producing the 1,4-cis adduct as the sole diastereoisomer. The deprotection was carried out using cerium ammonium nitrate followed by acid hydrolysis affording the enantipure α-amino acids.

Keywords

(S)-Deuterated-α-amino acids Diketopiperazine Asymmetric synthesis 

Notes

Acknowledgments

We express our gratitude to Sustainable Energy Ireland, administered by the Irish Research Council for Science, Engineering and Technology (IRCSET) for funding Elaine O’Reilly. We would also like to acknowledge the facilities of the Centre for Synthesis and Chemical Biology (CSCB), funded by the Higher Education Authorities Programme for Research in Third-Level Institutions (PRTLIs). We are grateful to Prof. Patrick Guiry for the use of his Perkin-Elmer 241 polarimeter.

References

  1. Bachmann S, Knudsen KR, Jorgensen KA (2004) Mimicking enzymatic transaminations: attempts to understand and develop a catalytic asymmetric approach to chiral α-amino acids. Org Biomol Chem 2:2044–2049CrossRefPubMedGoogle Scholar
  2. Balducci D, Lazzari I, Monari M, Piccinelli F, Porzi G (2009a) (S)-α-methyl, α-amino acids: a new stereocontrolled synthesis. Amino Acids. doi: 10.1007/s00726-009-0289-9
  3. Balducci D, Contaldi S, Lazzari I, Porzi G (2009b) A highly efficient stereocontrolled synthesis of (S)-2′,63/3/2010-dimethyltyrosine [(S)-DMT]. Tetrahedron Asymmetr 20:1398–1401CrossRefGoogle Scholar
  4. Bull SD, Davies SG, O’Shea MD (1998a) Stereoselective conjugate addition of organocuprates to a dehydroalanine derived diketopiperazine. J Chem Soc Perkin Trans 1(1):3657–3658CrossRefGoogle Scholar
  5. Bull SD, Davies, SG, Epstein SW, Ouzman VA (1998b) Chiral relay auxiliary for the synthesis of enantiomerically pure a-amino acids. Chem Commun 659–660Google Scholar
  6. Bull SD, Davies SG, Garner AC, Parkes AL, Roberts PM, Sellers TGR, Smith AD, Tamayo JA, Thomson JE, Vickers RJ (2007) On the origins of diastereocelectivity in the alkylation of diketopiperazine enolates. New J Chem 31:486–495CrossRefGoogle Scholar
  7. Davies SG, Garner AC, Ouzman VA, Roberts PM, Smith AD, Snow EJ, Thomson JE, Tamayo JA, Vickers RJ (2007) Diastereoselective synthesis of quaternary α-amino acids from diketopiperazine templates. Org Biomol Chem 5:2138–2147CrossRefPubMedGoogle Scholar
  8. Ducho C, Hamed RB, Batchelar ET, Sorensen JL, Odell B, Schofield CJ (2009) Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis. Org Biomol Chem 7:2770–2779CrossRefPubMedGoogle Scholar
  9. Felpin FX, Doris E, Wagner A, Valleix A, Rousseau B, Mioskowski C (2000) Rearrangement of α-amino cyclopropanone hydrate: a novel route to labeled amino acids. J Org Chem 66:305–308CrossRefGoogle Scholar
  10. Ferioli F, Piccinelli F, Porzi G, Sandri S (2002) Stereoselective synthesis of bis(α-amino acid) derivatives isosteric with cysteine. Part 4. Tetrahedron Asymmetr 13:1181CrossRefGoogle Scholar
  11. Gout E, Chesne S, Beguin CG, Pelmont J (1978) Kinetic studies with the use of Proton-Magnetic-Resonance Spectroscopy of the specific α-deuteration of amino acids by Escherichia coli aspartate aminotransferase. Biochem J 171:719–723PubMedGoogle Scholar
  12. Holding AN, Spencer JB (2008) Investigation into the mechanism of phenolic couplings during the biosynthesis of glycopeptide antibiotics. ChemBioChem 9:2209–2214CrossRefPubMedGoogle Scholar
  13. Moran GR, Derecskei-Kovacs A, Hillas PJ, Fitzpatrick PF (2000) On the catalytic mechanism of tryptophan hydroxylase. J Am Chem Soc 122:4535–4541CrossRefGoogle Scholar
  14. Nakanishi T, Miyazawa M, Sakakura M, Terasawa H, Takahashi H, Shimada I (2002) Determination of the interface of a large protein complex by transferred cross-saturation measurements. J Mol Biol 318:245–249CrossRefPubMedGoogle Scholar
  15. O’Reilly E, Lestini E, Balducci D, Paradisi F (2009) One-step diketopiperazine synthesis using phase transfer catalysis. Tetrahedron Lett 50:1748–1750CrossRefGoogle Scholar
  16. O’Reilly E, Pes L, Paradisi F (2010) From amines to diketopiperazines: a one-pot approach. Tetrahedron Lett 51:1696–1697Google Scholar
  17. Oba M, Terauchi T, Owari Y, Imai Y, Motoyamab I, Nishiyama K (1998) Stereo-divergent synthesis of l-threo- and l-erythro-[2, 3–2H2]amino acids using optically active dioxopiperazine as a chiral template. J Chem Soc Perkin Trans 1:1275–1281CrossRefGoogle Scholar
  18. Oba M, Iwasaki A, Hitokawa H, Ikegame T, Banba H, Ura K, Takamura T, Nishiyama K (2006) Preparation of l-serine and l-cystine stereospecifically labeled with deuterium at the β-position. Tetrahedron Asymmetr 17:1890–1894CrossRefGoogle Scholar
  19. Ong S-E, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1:376–386CrossRefPubMedGoogle Scholar
  20. Orena M, Porzi G, Sandri S (1992) Diastereoselective alkylation of (3S)- and (3R)-3-methylpiperazine-2, 5-dione derivatives. A convenient approach to both (S)- and (R)-alanine. J Org Chem 57:6532CrossRefGoogle Scholar
  21. Orena M, Porzi G, Sandri S (1993) (3R)-Methylpiperazine-2 and (3S)-methylpiperazine-2,5-dione derivatives as useful intermediates in the enantioselective synthesis of alpha-amino esters. J Chem Res Synop 318Google Scholar
  22. Paradisi F, Porzi G, Rinaldi S, Sandri S (2000a) A simple asymmetric synthesis of (+)- and (−)-2,6-diaminopimelic acids. Tetrahedron Asymmetr 11:1259CrossRefGoogle Scholar
  23. Paradisi F, Porzi G, Rinaldi S, Sandri S (2000b) Stereoselective synthesis of α, α′-diamino-dicarboxylic acids part 2. Tetrahedron Asymmetr 11:4617CrossRefGoogle Scholar
  24. Paradisi F, Piccinelli F, Porzi G, Sandri S (2002) Enantioselective synthesis of 2, 6-diaminopimelic acid derivatives. Part 3. Tetrahedron Asymmetr 13:497CrossRefGoogle Scholar
  25. Pearce DA, Sargeson AM, Hammershoi A, Harrowfield JM (2000) A simple regiospecific strategy for labelling hydrogen atoms in α-amino acids. Chem Commun 2431–2432Google Scholar
  26. Piccinelli F, Porzi G, Sandri M, Sandri S (2003) Stereocontrolled synthesis of enantiomerically pure unsaturated analogues of 2, 6-DAP. Part 5. Tetrahedron Asymmetr 14:393CrossRefGoogle Scholar
  27. Porzi G, Sandri S (1994) Synthesis of (3R, 6R)- and (3S, 6S)-3, 6-dialkylpiperazin-2, 5-dione derivatives as useful intermediates to both (R) and (S) α-aminoacids. Tetrahedron Asymmetr 5:453–464CrossRefGoogle Scholar
  28. Rose J, Leeson P, Gani D (1995) Stereospecific synthesis of α-deuterated α-amino acids: regiospecific deuteration of chiral 3-isopropyl-2, 5-dimethoxy-3, 6-dihydropyrazines. J Chem Soc Perkin Trans 1:157–165CrossRefGoogle Scholar
  29. Sattler M, Fesik SW (1996) Use of deuterium labeling in NMR: overcoming a sizeable problem. Structure 4:1245–1249CrossRefPubMedGoogle Scholar
  30. Schöllkopf U, Groth U, Deng C (1891) Enantioselective syntheses of (R)-amino acids using L-valine as chiral agent. Angew Chem Int Ed Engl 20:798–799CrossRefGoogle Scholar
  31. Schöllkopf U, Hartwig W, Groth U (1979) Enantioselective synthesis of α-Methyl-α-aminocarboxylic acids by alkylation of the lactim ether of cyclo-(L-Ala-L-Ala). Angew Chem Int Ed Engl 18:863–864CrossRefGoogle Scholar
  32. Smith AD, Bull SD, Davies SG, Epstein SW, Garner AC, Mujtaba N, Tamayo JA, Watkin DJ (2006) Enantiodiscrimination of racemic electrophiles using diketopiperazine enolates: asymmetric synthesis of methyl 2–amino-3 aryl aspartates and 3-methyl-aspartates. Tetrahedron 62:7911–7925CrossRefGoogle Scholar
  33. Takeuchi K, Ng E, Malia T, Wagner G (2007) 1-13C amino acid selective labeling in a 2H 15 N background for NMR studies of large proteins. J Biomol NMR 38:89–98CrossRefPubMedGoogle Scholar
  34. Veenstra TD, Martinovic S, Anderson GA, Pasa-Tolic L, Smith RD (2000) Proteome analysis using selective incorporation of isotopically labeled amino acids. J Am Soc Mass Spectrom 11:78–82CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.UCD School of Chemistry and Chemical BiologyCentre for Synthesis and Chemical BiologyDublin 4Ireland

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