Skip to main content
SpringerLink
Log in

Synthesis of orthogonally protected l-threo-β-ethoxyasparagine

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

Abstract

Orthogonally protected l-threo-β-ethoxyasparagine (Fmoc-EtOAsn(Trt)-OH, 1) was synthesized from diethyl (2S,3S)-2-azido-3-hydroxysuccinate 2 in eight steps as a building block for solid-phase peptide synthesis. The starting material is easily available in multi-gram scale from d-diethyltartrate. The transformation steps reported here are robust and scalable. Thus, a significant amount of 1 (1.8 g) was obtained in 21% overall yield. The synthesis reported is also expected to be useful for the preparation of other O-substituted l-threo-β-hydroxyasparagine derivatives.

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

Scheme 1
Scheme 2

Similar content being viewed by others

Abbreviations

ACN:

Acetonitrile

DIEA:

N,N-Diisopropylethylamine

DMF:

N,N-Dimethylformamide

EDC:

N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide

EtOAc:

Ethyl acetate

Fmoc-OSu:

N-(9-Fluorenylmethoxycarbonyloxy) succinimide

HOAc:

Acetic acid

TLC:

Thin-layer chromatography

References

  • Aikins JA, Haurez M, Rizzo JR, Van Hoeck J-P, Brione W, Kestemont J-P, Stevens C, Lemair X, Stephenson GA, Marlot E, Forst M, Houpis IN (2005) Synthesis of a peroxime proliferator activated receptor (PPAR) α/γ agonist via stereocontrolled Williamson ether synthesis and stereospecific SN2 reaction of S-2-chloro propionic acid with phenoxides. J Org Chem 70:4695–4705

    Article  CAS  PubMed  Google Scholar 

  • Albericio F, Burger K, Cupido T, Ruiz J, Spengler J (2005) Application of hexafluoroacetone as protecting and activating reagent in solid phase peptide and depsipeptide synthesis. Arkivoc 2005(vi):191–199

    Google Scholar 

  • Boger DL, Lee RJ, Bounaud P-Y, Meier P (2000) Asymmetric synthesis of orthogonally protected l-threo-β-hydroxyasparagine. J Org Chem 65:6770–6772

    Article  CAS  PubMed  Google Scholar 

  • Charvillon FB, Amouroux R (1997) Synthesis of 3-hydroxylated analogs of d-aspartic acid β-hydroxamate. Synthetic Commun 27:395–403

    Article  CAS  Google Scholar 

  • Guzmán-Martinez A, VanNieuwenhze MS (2007) An operationally simple and efficient synthesis of orthogonally protected l-threo-β-hydroxyasparagine. Synlett 1513–1516

  • Parmenon C, Guillard J, Caignard D-H, Hennuyer N, Staels B, Audinot-Bouchez V, Boutin J-A, Dacquet C, Ktorza A, Viaud-Massuard M-C (2008) 4, 4-Dimethyl-1, 2, 3, 4-tetrahydroquinoline-based PPAR α/γ agonists. Part I: Synthesis and pharmacological evaluation. Bioorg Med Chem Lett 18:1617–1622

    Article  CAS  PubMed  Google Scholar 

  • Saito S, Komada K, Moriwake T (1996) Diethyl (2S, 3R)-2-(N-tert-butoxycarbonyl)amino-3-hydroxysuccinate. Org Synth 73:184–200

    CAS  Google Scholar 

  • Spengler J, Boettcher C, Albericio F, Burger K (2006) Hexafluoroacetone as protecting and activating reagent: new routes to amino, hydroxy, and mercapto acids and their application for peptide and glyco- and depsipeptide modification. Chem Rev 106:4728–4746

    Article  PubMed  Google Scholar 

  • Weygand F, Steglich W, Bjarnason J (1968) Easily cleavable protective groups for acid amide groups. III. Derivatives of asparagine and glutamine with 2, 4-dimethoxybenzyl- and 2, 4, 6-trimethoxybenzyl-protected amide groups. Chem Ber 101:3642–3648

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are deeply indebted to Professor Klaus Burger, who inspired the HFA chemistry, for his continuous support. This study was partially funded by PharmaMar S.A.I., CICYT (CTQ2006-03794), the Generalitat de Catalunya (2009SGR 1024), the Barcelona Science Park and the Institute for Research in Biomedicine.

Author information

Authors and Affiliations

  1. Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain

    Jan Spengler, Marta Pelay, Judit Tulla-Puche & Fernando Albericio

  2. CIBER-BBN, Networking Centre on Bioengineering Biomaterials and Nanomedicine, Barcelona Science Park, University of Barcelona, Baldiri Reixac 10, 08028, Barcelona, Spain

    Jan Spengler, Marta Pelay, Judit Tulla-Puche & Fernando Albericio

  3. Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028, Barcelona, Spain

    Fernando Albericio

Authors
  1. Jan Spengler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Pelay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Judit Tulla-Puche
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernando Albericio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jan Spengler or Fernando Albericio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spengler, J., Pelay, M., Tulla-Puche, J. et al. Synthesis of orthogonally protected l-threo-β-ethoxyasparagine. Amino Acids 39, 161–165 (2010). https://doi.org/10.1007/s00726-009-0389-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-009-0389-6

Keywords

Search

Navigation