Skip to main content
SpringerLink
Log in

A direct method for the synthesis of orthogonally protected furyl- and thienyl- amino acids

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

Abstract

The synthesis of unnatural amino acids plays a key part in expanding the potential application of peptide-based drugs and in the total synthesis of peptide natural products. Herein, we report a direct method for the synthesis of orthogonally protected 5-membered heteroaromatic amino acids.

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

Fig. 1
Fig. 2
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5

Similar content being viewed by others

References

  • Barder TE, Walker SD, Martinelli JR, Buchwald SL (2005) New catalysts for Suzuki-Miyaura coupling processes: scope and studies of the effect of ligand structure. J Am Chem Soc 127:4685–4696

    Article  CAS  PubMed  Google Scholar 

  • Capek P, Pohl R, Hocek M (2004) A facile and efficient synthesis of (Purin-6-yl)alanines. J Org Chem 69:7985–7988

    Article  CAS  PubMed  Google Scholar 

  • Clausen RP, Naur P, Kristensen AS, Greenwood JR, Strange M, Brauner-Osborne H, Jensen AA, Nielsen AST, Geneser U, Ringgaard LM, Nielsen B, Pickering DS, Brehm L, Gajhede M, Krogsgaard-Larsen P, Kastrup JS (2009) The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue: synthesis, molecular pharmacology, and biostructural characterization. J Med Chem 52:4911–4922

    Article  CAS  PubMed  Google Scholar 

  • Cobb SL, Vederas JC (2007) A concise stereoselective synthesis of orthogonally protected lanthionine and β-ethyllanthionine. Org Biomol Chem 5:1031–1038

    Article  CAS  PubMed  Google Scholar 

  • Colgin N, Flinn T, Cobb SL (2011) Synthesis and properties of MIDA boronate containing aromatic amino acids: new peptide building blocks. Org Biomol Chem 9:1864–1870

    Article  CAS  PubMed  Google Scholar 

  • Deboves HJC, Montalbetti CAGN, Jackson RFW (2001) Direct synthesis of Fmoc-protected amino acids using organozinc chemistry: application to olymethoxylated phenylalanines and 4-oxoamino acids. J Chem Soc, Perkin Trans 1(16):1876–1884

    Article  Google Scholar 

  • Eerland MF, Hedberg C (2012) Design and synthesis of an Fmoc-SPPS-compatible amino acid building block mimicking the transition state of phosphohistidine phosphatase. J Org Chem 17:2047–2052

    Article  Google Scholar 

  • Hilker M, Hberlein C, Trauer U, Hilker Monika, Hberlein Christopher, Trauer Ute, Bünnige M, Vicentini M, Schulz S (2010) How to spoil the taste of insect prey? A novel feeding deterrent against ants released by larvae of the alder leaf beetle, Agelastica alni. ChemBioChem 11:1720–1726

    Article  CAS  PubMed  Google Scholar 

  • Jackson RFW, Wythes MJ, Wood A (1989) Synthesis of enantiomerically pure protected β-aryl alanines. Tetrahedron Lett 30:5941–5944

    Article  CAS  Google Scholar 

  • Jackson RFW, Wishart N, Wood A, James K, Wythes JM (1992) Preparation of enantiomerically pure protected 4-oxo α-amino acids and 3-aryl α-amino acids from serine. J Org Chem 57:3397–3404

    Article  CAS  Google Scholar 

  • Jackson RFW, Moore RJ, Dexter CS, Elliot J, Mowbray CE (1998) Concise synthesis of enantiomerically pure phenylalanine, homophenylalanine, and bishomophenylalanine derivatives using organozinc chemistry: NMR studies of amino acid-derived organozinc reagents. J Org Chem 63:7875–7884

    Article  CAS  Google Scholar 

  • Jackson RFW, Rilatt I, Murray PJ (2004) Direct synthesis of unprotected phenols using palladium-catalysed cross coupling reactions of functionalised organozinc reagents. Org Biomol Chem 2(110):113

    Google Scholar 

  • Lilley M, Mambwe B, Jackson RFW, Muimo R (2014) 4-phosphotheiopheny-2-yl alanine: a new 5-membered analogue of phosphotyrosine. Chem Comm 50:9343–9345

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Freeland S (2006) On the evolution of the standard amino-acid alphabet. Genome Biol 7:102

    Article  PubMed Central  PubMed  Google Scholar 

  • Martin R, Buchwald SL (2008) Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc Chem Res 41:1461–1473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oswald CL, Carrillo-Márquez T, Caggiano L, Jackson RFW (2008) Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides. Tetrahedron 64:681–687

    Article  CAS  Google Scholar 

  • Partida-Martinez LP, de Looß CF, Ishida K, Ishida M, Roth M, Buder K, Hertweck C (2007) Rhizonin, the first mycotoxin isolated from the zygomycota, is not a fungal metabolite but is produced by bacterial endosymbionts. Appl Environ Microbiol 73:793–797

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perdih A, Dolenc MS (2011) Recent advances in the synthesis of unnatural alpha-amino acids—an updated version. Curr Org Chem 15:3750–3799

    Article  CAS  Google Scholar 

  • Rodriguez A, Millar DD, Jackson RFW (2003) Combined application of organozinc chemistry and one-pot hydroboration–Suzuki coupling to the synthesis of amino acids. Org Biomol Chem 1:973977

    Google Scholar 

  • Ross AJ, Lang HL, Jackson RFW (2010) Much improved conditions for the Negishi cross-coupling of iodoalanine derived zinc reagents with aryl halides. J Org Chem 75:245–248

    Article  CAS  PubMed  Google Scholar 

  • Ross AJ, Dreiocker F, Schäfer M, Oomens J, Meijer AJ, Pickup BT, Jackson RFW (2011) Evidence for the role of tetramethylethylenediamine in aqueous Negishi cross-coupling: synthesis of nonproteinogenic phenylalanine derivatives on water. J Org Chem 76:1727–1734

    Article  CAS  PubMed  Google Scholar 

  • Sabine A, Ulrich E, Bäurle S, Friedrich T, Grubert L, Koert U (2001) Quinone-annonaceous acetogenins: synthesis and complex I inhibition studies of a new class of natural product hybrids. Chem Eur J 7:993–1005

    Article  Google Scholar 

  • Schulz A, Busmann A, Kluver E, Schnebel M, Adermann K (2004) Stability and cleavage conditions of (2-Furyl)-L-alanine-containing peptides. Protein Pept Lett 11:601–606

    Article  CAS  PubMed  Google Scholar 

  • Tabanella S, Valancogne Jackson RFW (2003) Preparation of enantiomerically pure pyridyl amino acids from serine. Org Biomol Chem 1:4254–4261

    Article  CAS  PubMed  Google Scholar 

  • Tanaka M, Hikawa H, Yokoyama Y (2011) Convenient synthesis of chiral tryptophan derivatives using Negishi cross-coupling. Tetrahedron 67:5897–5901

    Article  CAS  Google Scholar 

  • Walker MA, Kaplita PK, Chen T, King DH (1997) Synthesis of all three regioisomers of pyridylalanine. Synlett 2:169–170

    Article  Google Scholar 

  • Wang L, Qu W, Lieberman B, Ploessel K, HF Funk (2010) Synthesis and in vitro evaluation of 18F labelled tyrosine derivatives as potential positron emission tomography (PET) imaging agents. Bioorg Med Chem Lett 20:3483–3485

    Google Scholar 

  • Zhang WH, Otting G, Jackson CJ (2013) Protein engineering with unnatural amino acids. Curr Oppin Chem Biol 23:581–587

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Engineering and Physical Science Research Council (ASH) and Cambridge Research Biochemicals Ltd.

Conflict of interest

The authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK

    Alex S. Hudson & Steven L. Cobb

  2. Cambridge Research Biochemicals Ltd, Billingham, Cleveland, TS23 4AZ, UK

    Laurent Caron & Neil Colgin

Authors
  1. Alex S. Hudson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laurent Caron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neil Colgin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven L. Cobb
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven L. Cobb.

Additional information

Handling Editor: P. Meffre.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 6932 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hudson, A.S., Caron, L., Colgin, N. et al. A direct method for the synthesis of orthogonally protected furyl- and thienyl- amino acids. Amino Acids 47, 779–785 (2015). https://doi.org/10.1007/s00726-014-1908-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-014-1908-7

Keywords

Search

Navigation