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An efficient and highly chemoselective N-Boc protection of amines, amino acids, and peptides under heterogeneous conditions

Abstract

A simple and efficient procedure for chemoselective mono-N-Boc protection of various structurally diverse amines, amino acids, and peptides with di-tert-butyl dicarbonate using Amberlyst-15 as catalyst in ethanol is described. The catalyst can be readily separated from the reaction products with simple filtration and recovered for direct reuse. No competitive side-reactions such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were observed.

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References

  1. Wuts PGM, Greene TW (2007) Greene’s protective group in organic synthesis, 4th ed. Wiley, New York

    Google Scholar 

  2. Raghavendra NS, Kumar BP, Longquin H (2006) Tetrahedron Lett 47:389

    Article  Google Scholar 

  3. Pope BM, Yamamoto X, Tarbell DS (1988) Org Synth Coll VI:418

    Google Scholar 

  4. Srinivasan N, Yurek-George AG (2005) Mol Diver 9:291

    Article  CAS  Google Scholar 

  5. Longenecker K, Hamilton GL, Stewart K, Lai C, Kopecka H, von Geldern TW, Madar DJ, Pei Z, Lubben TH, Zinker BA, Tian Z, Ballaron SJ, Stashko MA, Mika AK, Beno DWA, Kempf-Grote AJ, Black-Schaefer C, Sham HL, Trevillyan JM (2007) Bioorg Med Chem Lett 17:2005

    Article  Google Scholar 

  6. Merrifield RB (1964) J Am Chem Soc 86:304

    Article  CAS  Google Scholar 

  7. Satori G, Ballini R, Bigi F, Bosica G, Maggi R, Righi P (2004) Chem Rev 104:199

    Article  Google Scholar 

  8. Kocienski PJ (2000) Protecting groups. Georg Thieme Verlag, Stuttgart

    Google Scholar 

  9. Wuensch E (1974) Houben-Weyl, methods of organic chemistry, 4th edn. In: Mueller E, Bayer O, Meerwein H, Ziegler K (eds), Georg Thieme Verlag, Stuttgart, vol 15/1, p 46

  10. McOmie JFW (1973) Protective groups in organic chemistry. Plenum Press, London

    Google Scholar 

  11. Gross E, Meienhofer J (1981) The peptides. Academic Press, New York

    Google Scholar 

  12. Merrifield RB (1963) J Am Chem Soc 85:2149

    Article  CAS  Google Scholar 

  13. Lutz C, Lutz V, Knochel P (1998) Tetrahedron 54:6385

    Article  CAS  Google Scholar 

  14. Handy ST, Sabatini JJ, Zhang Y, Vulfova I (2004) Tetrahedron Lett 45:5057

    Article  CAS  Google Scholar 

  15. Khalil EM, Subasinghe NL, Johnson RL (1996) Tetrahedron Lett 37:3441

    Article  CAS  Google Scholar 

  16. Eunhorn J, Einhorn C, Luche JL (1991) Synlett 1:37

    Google Scholar 

  17. Kelly TA, McNeil DW (1994) Tetrahedron Lett 35:9003

    Article  CAS  Google Scholar 

  18. Darnbrough S, Mervic M, Condon SM, Burns CJ (2001) Synth Commun 31:3273

    Article  CAS  Google Scholar 

  19. Basel Y, Hassner A (2000) J Org Chem 65:6368

    Article  CAS  Google Scholar 

  20. Burk MJ, Allen JG (1997) J Org Chem 62:7054

    Article  CAS  Google Scholar 

  21. Grehn L, Ragnarsson U (1985) Angew Chem Int Ed 24:510

    Article  Google Scholar 

  22. Pandey RK, Dagade SP, Upadhyay RK, Dongare MK, Kumar P (2002) Arkivoc vii:28

  23. Sharma GVM, Reddy JJ, Lakshmi PS, Krishna PR (2004) Tetrahedron Lett 45:6963

    Article  CAS  Google Scholar 

  24. Bartoli G, Bosco M, Locatelli M, Marcantoni E, Massaccesi M, Melchiorr P, Sambri L (2004) Synlett 10:1794

    Google Scholar 

  25. Heydari A, Hosseini SE (2005) Adv Synth Catal 347:1929

    Article  CAS  Google Scholar 

  26. Chankeshwara SV, Chakraborti AK (2006) Tetrahedron Lett 47:1087

    Article  CAS  Google Scholar 

  27. Varala R, Nuvula S, Adapa SR (2006) J Org Chem 71:8283

    Article  CAS  Google Scholar 

  28. Heydari A, Kazem Shiroodi R, Hamadi H, Esfandyari M, Pourayoubi M (2007) Tetrahedron Lett 48:5865

    Article  CAS  Google Scholar 

  29. Chankeshwara SV, Chakraborti AK (2006) J Mol Catal A: Chem 253:198

    Article  CAS  Google Scholar 

  30. Das B, Verkateswarlu K, Krishnaiah M, Holla H (2006) Tetrahedron Lett 47:7551

    Article  CAS  Google Scholar 

  31. Suryakiran N, Prabhakar P, Srikanth Reddy T, Rajesh K, Venkateswarlu Y (2006) Tetrahedron Lett 47:8039

    Article  CAS  Google Scholar 

  32. Khaksar S, Heydari A, Tajbakhsh M, Vahdat SM (2008) Tetrahedron Lett 49:3527

    Article  CAS  Google Scholar 

  33. Heydari A, Khaksar S, Tajbakhsh M (2008) Synthesis 19:3126

    Google Scholar 

  34. Jahani F, Tajbakhsh M, Golchoubian H, Khaksar S (2011) Tetrahedron Lett 52:1260

    Article  CAS  Google Scholar 

  35. Meienhofer J, Kuromizu K (1974) Tetrahedron Lett 15:3259

    Article  Google Scholar 

  36. Ishihara K, Hasegama A, Yamamoto H (2001) Angew Chem Int Ed 40:4077

    Article  CAS  Google Scholar 

  37. Trost BM (1991) Science 254:1471

    Article  CAS  Google Scholar 

  38. Sheldon RA (1994) Chemtech 24:38

    Google Scholar 

  39. Anastas PT, Warner JC (1998) Green chemistry: theory and practice. Oxford University Press, UK

    Google Scholar 

  40. Tajbakhsh M, Heydari A, Alinezhad H, Ghanei M, Khaksar S (2008) Synthesis 3:352

    Google Scholar 

  41. Tajbakhsh M, Heydari A, Khalilzadeh MA, Lakouraj MM, Zamenian B, Khaksar S (2007) Synlett 15:2347

    Google Scholar 

  42. Lakouraj MM, Tajbakhsh M, Tashakkorian H (2007) Monatsh Chem 138:83

    Article  CAS  Google Scholar 

  43. Tajbakhsh M, Hosseinzadeh R, Lasemi Z (2004) Synlett 4:635

    Google Scholar 

  44. Kumar KS, Iqbal J, Pal M (2009) Tetrahedron Lett 50:6244

    Article  CAS  Google Scholar 

  45. Liu YS, Zhao C, Bergbreiter DE, Romo D (1998) J Org Chem 63:3471

    Article  CAS  Google Scholar 

  46. Vilaivan T (2006) Tetrahedron Lett 47:6739

    Article  CAS  Google Scholar 

  47. Jia X, Huang Q, Li J, Li S, Yang Q (2007) Synlett 5:806

  48. Chankeshwara SV, Chakraborti AK (2006) Org Lett 8:3259

    Article  CAS  Google Scholar 

  49. Dieter RK, Li S (1997) J Org Chem 62:7726

    Article  CAS  Google Scholar 

  50. Norman MH, Rigdon GC, Hall WR, Navas F III (1996) J Med Chem 39:1172

    Article  CAS  Google Scholar 

  51. Dondoni A, Perrone D, Semola T (1995) Synthesis 2:181

    Google Scholar 

  52. Green R, Taylor PJM, Bull SD, James TD, Mahon MF, Merritt AT (2003) Tetrahedron: Asymmetry 14:2619

  53. Marcantoni E, Massaccesi M, Torregiani E (2001) J Org Chem 66:4430

    Article  CAS  Google Scholar 

  54. Anderson GW, Mcgregor AC (1957) J Am Chem Soc 79:6180

    Article  CAS  Google Scholar 

  55. Myers AG, Gleason JL, Yoon T, Kung DW (1997) J Am Chem Soc 119:656

    Article  CAS  Google Scholar 

  56. Itoh M, Hagiwara D, Kamiya T (1975) Tetrahedron Lett 49:4393

    Article  Google Scholar 

  57. Thaqi A, McCluskey A, Scott JL (2008) Tetrahedron Lett 49:6962

    Article  CAS  Google Scholar 

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Acknowledgments

Financial support of this work by the Research Council of Mazandaran University is gratefully acknowledged.

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Correspondence to Mahmood Tajbakhsh.

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Jahani, F., Tajbakhsh, M., Khaksar, S. et al. An efficient and highly chemoselective N-Boc protection of amines, amino acids, and peptides under heterogeneous conditions. Monatsh Chem 142, 1035 (2011). https://doi.org/10.1007/s00706-011-0534-2

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  • DOI: https://doi.org/10.1007/s00706-011-0534-2

Keywords

  • Amberlyst-15
  • Di-tert-butyl dicarbonate
  • Protection
  • Amine
  • Amino acid
BOC Protected Amino Acids