Skip to main content
SpringerLink
Log in

One-Pot Synthesis of Nα-Protected Amino/Peptide O-benzyl Hydroxamates and Acylaminoxy Dipeptides Employing Hydroxamic Acid

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

The direct conversion of simple and sterically hindered Nα-protected amino/peptide hydroxamic acids to O-benzyl hydroxamates employing K2CO3, tetrabutylammonium bromide and benzyl bromide is described. In addition, Cbz-Ala-CONHOH and Cbz-Phe-CONHOH derived acylaminoxy peptides 3j and 3k have also been prepared. The method is of importance in the view of easy availability of precursors, catalyst and reaction conditions. All the products are obtained in moderate to good yields.

Graphical Abstract

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
Scheme 3
Fig. 1
Scheme 4
Fig. 2

Similar content being viewed by others

References

  • Chary MV, Keerthysri NC, Vapallapati SVN, Lingaiah N, Kantevari S (2008) Tetrabutylammonium bromide (TBAB) in isopropanol: an efficient, novel, neutral and recyclable catalytic system for the synthesis of 2,4,5-trisubstituted imidazoles. Catal Commun 9:2013

    Article  CAS  Google Scholar 

  • Chimiak A, Milewska MJ, Herz W, Grisebach H, kirbyb GW, Tamm (1988) Progress in the chemistry of organic natural products. Springer, New York, p 203

    Google Scholar 

  • Dev D, Palakurthy BN, Thalluri K, Chandra J, Mandal B (2014) Ethyl 2-Cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o-NosylOXY): a recyclable coupling reagent for racemization-free synthesis of peptide, amide, hydroxamate, and ester. J Org Chem 79:5420

    Article  CAS  PubMed  Google Scholar 

  • Duvic M, Vu J (2007) Update on the treatment of cutaneous T-cell lymphoma (CTCL): focus on vorinostat. Biol Targets Ther 1:377

    CAS  Google Scholar 

  • Emary T (1987) In: Sigel H (ed) Metal ions in biological systems, vol 7. Marcel Dekker, New York, p 77

    Google Scholar 

  • Gissot A, Volonterio A, Zanda M (2005) One-step synthesis of O-benzyl hydroxamates from unactivated aliphatic and aromatic esters. J Org Chem 70:6925

    Article  CAS  PubMed  Google Scholar 

  • Jung M (2001) Inhibitors of histone deacetylase as new anticancer agents. Curr Med Chem 8:1505

    Article  CAS  PubMed  Google Scholar 

  • Kantevari S, Chary MV, Das APR, Srinivasu VNV, Lingaiah N (2008) Catalysis by an ionic liquid: highly efficient solvent-free synthesis of aryl-14H-dibenzo[aj]xanthenes by molten tetrabutylammonium bromide under conventional and microwave heating. Catal Commun 9:1575

    Article  CAS  Google Scholar 

  • Katritzky AR, Avan L, Tala SR (2009) Efficient preparation of aminoxyacyl amides, aminoxy hybrid peptides and alpha-aminoxy peptides. J Org Chem 74:8690

    Article  CAS  PubMed  Google Scholar 

  • Krishnamurthy M, Vishwanatha TM, Nageswara RP, Panduranga V, Sureshbabu VV (2015) Iodine-mediated oxidative coupling of hydroxamic acids with amines towards a new peptide bond formation. Synlett 26:2565

    Article  CAS  Google Scholar 

  • Miller MJ (1986) Hydroxamate approach to the synthesis of lactam antibiotics. Acc Chem Res 19:49

    Article  CAS  Google Scholar 

  • Miller MJ (1989) Syntheses and therapeutic potential of hydroxamic acid based siderophores and analogues. Chem Rev 89:1563

    Article  CAS  Google Scholar 

  • Nageswara RP, Basavaprabhu, Sureshbabu VV (2014) Facile synthesis of Nα-protected amino/peptide hydroxamic acids mediated by COMU. Int J Pept Res Ther 20:377

    Article  Google Scholar 

  • Nageswara RP, Sureshbabu VV (2014) Iodine-accelerated synthesis of Nα-urethane protected amino/peptide hydroxamic acids from amino/peptide thioacids. IJC-B 53:1430

    Google Scholar 

  • Narendra N, Chennakrishnareddy G, Sureshbabu VV (2009) Application of carbodiimide mediated lossen rearrangement for the synthesis of α-ureidopeptides and peptidyl ureas employing N-urethane a-amino/peptidyl hydroxamic acids. Org Biomol Chem 7:3520

    Article  CAS  PubMed  Google Scholar 

  • Palakurthy BN, Dev D, Paikaray S, Chaudhury S, Mandal B (2014) Synthesis of O-benzyl hydroxamates employing the sulfonate esters of N-hydroxybenzotriazole. RSC Adv 4:7952

    Article  CAS  Google Scholar 

  • Pirrung CM, Chau HL (1995) A convenient procedure for the preparation of amino acid hydroxamates from esters. J Org Chem 60:8084

    Article  CAS  Google Scholar 

  • Ramasamy K, Olsen KR, Emery T (1981) N-Methylation of O-benzyl-.alpha.-N-(alkoxycarbonyl)-.alpha.-amino acid hydroxamate derivatives. J Org Chem 46:5438

    Article  CAS  Google Scholar 

  • Ranu BC, Das A, Samanta S (2002) Catalysis by ionic liquids: solvent-free efficient transthioacetalisation of acetals by molten tetrabutylammonium bromide. J Chem Soc Perkin Trans 1:1520

    Article  Google Scholar 

  • Ranu BC, Dey SS, Hajra A (2003) Catalysis by an ionic liquid: efficient conjugate addition of thiols to electron deficient alkenes catalyzed by molten tetrabutylammonium bromide under solvent-free conditions. Tetrahedron 59:2417

    Article  CAS  Google Scholar 

  • Siddiqui SA, Narkhede UC, Palimkar SS, Daniel T, Loholi RJ, Srinivasan KV (2005) Room temperature ionic liquid promoted improved and rapid synthesis of 2,4,5-triaryl imidazoles from aryl aldehydes and 1,2-diketones or α-hydroxyketone. Tetrahedron 61:3539

    Article  CAS  Google Scholar 

  • Vasantha B, Hemantha HP, Sureshbabu VV (2010) 1-Propanephosphonic acid cyclic anhydride (T3P) as an efficient promoter for the lossen rearrangement: application to the synthesis of urea and carbamate derivatives. Synthesis 17:299

    Google Scholar 

  • Vasanthkumar RG, Sureshbabu VV (2003) Direct synthesis of Fmoc protected amino acid hydroxamates from acid chlorides mediated by magnesium oxide. Tetrahedron Lett 44:4099

    Article  Google Scholar 

  • Weber G (1983) Biochemical strategy of cancer cells and the design of chemotherapy: G. H. A. Clowes memorial lecture. Cancer Res 43:3466

    CAS  PubMed  Google Scholar 

  • Whittaker M, Floyd CD, Brown P, Gearing AJH (1999) Design and therapeutic application of matrix metalloproteinase inhibitors. Chem Rev 99:2735

    Article  CAS  PubMed  Google Scholar 

  • Yadav DK, Yadav AK, Srivastava VP, Watal G, Yadav LS (2012) Bromodimethylsulfonium bromide (BDMS)-mediated lossen rearrangement: synthesis of unsymmetrical ureas. Tetrahedron Lett 53:2890

    Article  CAS  Google Scholar 

  • Yoganathan S, Miller SJ (2003) N-Methylimidazole-catalyzed synthesis of carbamates from hydroxamic acids via the lossen rearrangement. Org Lett 15:602

    Article  Google Scholar 

Download references

Acknowledgments

We sincerely thankful to Council of Scientific and Industrial Research (CSIR) Grant No. 02(0149)/13/EMR-II Government of India, New Delhi for financial support.

Author information

Authors and Affiliations

  1. #109, Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Bangalore University, Dr. B. R. Ambedkar Veedhi, Bangalore, 560 001, India

    Muniyappa Krishnamurthy, N. R. Sagar & Vommina V. Sureshbabu

Authors
  1. Muniyappa Krishnamurthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. R. Sagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vommina V. Sureshbabu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vommina V. Sureshbabu.

Ethics declarations

Conflict of interest

Muniyappa Krishnamurthy, Basavaprabhu, Vommina V. Sureshbabu declare that they have no conflict of interest.

Informed consent

Authors declare that there is no informed consent in the article.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by the any of the authors

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krishnamurthy, M., Sagar, N.R. & Sureshbabu, V.V. One-Pot Synthesis of Nα-Protected Amino/Peptide O-benzyl Hydroxamates and Acylaminoxy Dipeptides Employing Hydroxamic Acid. Int J Pept Res Ther 23, 191–197 (2017). https://doi.org/10.1007/s10989-016-9550-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-016-9550-8

Keywords

Search

Navigation