Advertisement

Intramolecular N-Acyliminium Cascade (INAIC) Reactions in Cyclization of Peptide-Like Molecules

  • Frederik Diness
  • Yuanyuan Wang
  • Morten MeldalEmail author
Chapter
  • 520 Downloads
Part of the Topics in Heterocyclic Chemistry book series (TOPICS, volume 52)

Abstract

The present review describes the implementation of N-acyliminium ion chemistry of peptide aldehydes in the context of solid phase peptide synthesis. The INAIC reaction is a cascade reaction in which an aldehyde, located within a peptide, initially reacts with proximate and weakly nucleophilic amide nitrogen to form a hydroxylactam. Under acidic conditions the hydroxylactam eliminates water and produces highly reactive N-acyliminium ions. These in turn reacts with high stereospecificity with any nucleophile nearby in the peptide, including C-nucleophiles or even a second amide nitrogen to form two new heterocyclic rings which can both be 5 membered or they can be 5,6; 6,5; 6,6; or 5,7 membered. In this manner simple peptides can be transformed into interesting heterocycles with structures that may interact with 7TM receptors and are valuable in drug screening programs. In addition to amides, carbamoyl nitrogens can also act as the primary nucleophile in the analogous INCIC reaction, thus expanding the scope of these reactions significantly. Due to the high reactivity of the N-acyl-iminium ions deactivated C-nucleophiles such as dichlorobenzene rings may be employed in addition to the reactive C-nucleophiles, e.g., indoles commonly used in the related Pictet-Spengler reaction. In this manner complex annulated tetrahydro β-carbolines and tetrahydroisoquinoline can be synthesized within the peptide framework. The scope of the INAIC and INCIC reactions is significant with more than 40 different heterocyclic scaffolds currently synthesized and even more new scaffolds possible.

Keywords

Cascade reaction Complex heterocycles Intramolecular cyclization N-acyliminium ion chemistry Peptide aldehyde Peptide alkaloids Peptide cyclization Solid phase INAIC reaction 

References

  1. 1.
    Tornøe CW, Meldal M (2001) Wave of the future. In: Lebl M, Hougten R (eds) Proceedings of 17th American peptide symposium. Kluwer Academic Publishers, San Diego, pp 263–264. doi: 10.1007/978-94-010-0464-0_119 Google Scholar
  2. 2.
    Tornøe CW, Christensen C, Meldal M (2002) J Org Chem 67:3057–3064CrossRefGoogle Scholar
  3. 3.
    Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) Angew Chem Int Ed 41:2596–2599CrossRefGoogle Scholar
  4. 4.
    Meldal M, Tornøe CW (2008) Chem Rev 108:2952–3015CrossRefGoogle Scholar
  5. 5.
    Diness F, Schoffelen S, Meldal M (2015) Advances in merging triazoles with peptides and proteins, Topics in Heterocyclic Chemistry. Springer, Berlin/Heidelberg, pp 1–38. doi: 10.1007/7081_2015_192 Google Scholar
  6. 6.
    Mannich C, Krösche W (1912) Arch Pharm 250:647–667CrossRefGoogle Scholar
  7. 7.
    Petasis NA, Akritopoulou I (1993) Tetrahedron Lett 34:583–586CrossRefGoogle Scholar
  8. 8.
    Pictet A, Spengler T (1911) Chem Ber 44:2030–2036CrossRefGoogle Scholar
  9. 9.
    Nielsen TE, Meldal M (2004) J Org Chem 69:3765–3773CrossRefGoogle Scholar
  10. 10.
    Diness F, Beyer J, Meldal M (2006) Chem Eur J 12:8056–8066CrossRefGoogle Scholar
  11. 11.
    Rademann J, Meldal M, Bock K (1999) Chem Eur J 5:1218–1225CrossRefGoogle Scholar
  12. 12.
    Maryanoff BE, Zhang H-C, Cohen JH, Turchi IJ, Maryanoff CA (2004) Chem Rev 104:1431–1628CrossRefGoogle Scholar
  13. 13.
    Cox ED, Cook JM (1995) Chem Rev 95:1797–1842CrossRefGoogle Scholar
  14. 14.
    Brase S, Gil C, Knepper K (2002) Bioorg Med Chem 10:2415–2437CrossRefGoogle Scholar
  15. 15.
    Meldal M, Tornoe CW, Nielsen TE, Diness F, Le Quement ST, Christensen CA, Jensen JF, Worm-Leonhard K, Groth T, Bouakaz L, Wu B, Hagel G, Keinicke L (2010) Biopolymers 94:161–182CrossRefGoogle Scholar
  16. 16.
    Le Quement ST, Petersen R, Meldal M, Nielsen TE (2010) Biopolymers 94:242–256CrossRefGoogle Scholar
  17. 17.
    Nielsen TE, Meldal M (2009) Curr Opin Drug Discov Devel 12:798–810Google Scholar
  18. 18.
    Groth T, Meldal M (2001) J Comb Chem 3:45–63CrossRefGoogle Scholar
  19. 19.
    Nielsen TE, Meldal M (2005) J Comb Chem 7:599–610CrossRefGoogle Scholar
  20. 20.
    Casnati G, Dossena A, Pochini A (1972) Tetrahedron Lett 52:5277–5280CrossRefGoogle Scholar
  21. 21.
    Sharma A, Singh M, Rai NN, Sawant D (2013) Beilstein J Org Chem 9:1235–1242CrossRefGoogle Scholar
  22. 22.
    Le Quement ST, Nielsen TE, Meldal M (2008) J Comb Chem 10:447–455CrossRefGoogle Scholar
  23. 23.
    Nielsen TE, Le Quement ST, Meldal M (2005) Org Lett 7:3601–3604CrossRefGoogle Scholar
  24. 24.
    Lee SC, Park SB (2006) J Comb Chem 8:50–57CrossRefGoogle Scholar
  25. 25.
    Diness F, Beyer J, Meldal M (2004) QSAR Comb Sci 23:130–144CrossRefGoogle Scholar
  26. 26.
    Diness F, Meldal M (2009) Chem Eur J 15:7044–7047CrossRefGoogle Scholar
  27. 27.
    Nahm S, Weinreb SM (1981) Tetrahedron Lett 22:3815–3818CrossRefGoogle Scholar
  28. 28.
    Wen JJ, Crews CM (1998) Tetrahedron 9:1855–1858CrossRefGoogle Scholar
  29. 29.
    Christensen C, Tornøe CW, Meldal M (2004) QSAR Comb Sci 23:109–116CrossRefGoogle Scholar
  30. 30.
    Le Quement ST, Nielsen TE, Meldal M (2007) J Comb Chem 9:1060–1072CrossRefGoogle Scholar
  31. 31.
    Berry JM, Howard PW, Thurston DE (2000) Tetrahedron Lett 41:6171–6174CrossRefGoogle Scholar
  32. 32.
    Dahlqvist A, Olsson I, Nordén Å (1965) J Histochem Cytochem 13:423–430CrossRefGoogle Scholar
  33. 33.
    Geoghegan KF, Stroh JG (1992) Bioconjug Chem 3:138–146CrossRefGoogle Scholar
  34. 34.
    Li X, Zhang L, Hall SE, Tam JP (2000) Tetrahedron Lett 41:4069–4073CrossRefGoogle Scholar
  35. 35.
    Petersen R, Le Quement ST, Nielsen TE (2014) Angew Chem Int Ed 53:11778–11782CrossRefGoogle Scholar
  36. 36.
    Scott WL, Martynow JG, Huffman JC, O'Donnell MJ (2007) J Am Chem Soc 129:7077–7088CrossRefGoogle Scholar
  37. 37.
    Nielsen TE, Meldal M (2005) Org Lett 7:2695–2698CrossRefGoogle Scholar
  38. 38.
    Groth T, Meldal M (2001) J Comb Chem 3:34–44CrossRefGoogle Scholar
  39. 39.
    Karpov AS, Oeser T, Müller TJJ (2004) Chem Commun 15021503Google Scholar
  40. 40.
    Hansen CL, Clausen JW, Ohm RG, Ascic E, Le Quement ST, Tanner D, Nielsen TE (2013) J Org Chem 78:12545–12565CrossRefGoogle Scholar
  41. 41.
    Ascic E, Jensen JF, Nielsen TE (2011) Angew Chem Int Ed 50:5188–5191CrossRefGoogle Scholar
  42. 42.
    Silveira CC, Felix LA, Braga AL, Kaufman TS (2005) Org Lett 7:3701–3704CrossRefGoogle Scholar
  43. 43.
    Diness F, Meldal M (2015) Eur J Org Chem 7:1433–1436CrossRefGoogle Scholar
  44. 44.
    Lee SC, Choi SY, Chung YK, Park SB (2006) Tetrahedron Lett 47:6843–6847CrossRefGoogle Scholar
  45. 45.
    Li X, Zhang L, Zhang W, Hall SE, Tam JP (2000) Org Lett 2:3075–3078CrossRefGoogle Scholar
  46. 46.
    Komnatnyy VV, Givskov M, Nielsen TE (2012) Chem Eur J 18:16793–16800CrossRefGoogle Scholar
  47. 47.
    Chanda K, Chou CT, Lai JJ, Lin SF, Yellol GS, Sun CM (2011) Mol Divers 15:569–581CrossRefGoogle Scholar
  48. 48.
    Fridkin M, atchornik A, Katchalski E (1965) J Am Chem Soc 87:4646–4648CrossRefGoogle Scholar
  49. 49.
    Ganesan A (2006) Mini Rev Med Chem 6:3–10CrossRefGoogle Scholar
  50. 50.
    Bonnet D, Ganesan A (2002) J Comb Chem 4:546–548CrossRefGoogle Scholar
  51. 51.
    Fantauzzi PP, Yager KM (1998) Tetrahedron Lett 39:1291–1294CrossRefGoogle Scholar
  52. 52.
    Kuo FM, Tseng MC, Yen YH, Chu YH (2004) Tetrahedron 60:12075–12084CrossRefGoogle Scholar
  53. 53.
    Wang H, Ganesan A (1999) Org Lett 1:1647–1649CrossRefGoogle Scholar
  54. 54.
    Kundu B, Sawant D, Chhabra R (2005) J Comb Chem 7:317–321CrossRefGoogle Scholar
  55. 55.
    Deaudelin P, Lubell WD (2008) Org Lett 10:2841–2844CrossRefGoogle Scholar
  56. 56.
    Nielsen TE, Le Quement S, Meldal M (2005) Tetrahedron Lett 46:7959–7962CrossRefGoogle Scholar
  57. 57.
    Dondas HA, Grigg R, MacLachlan WS, MacPherson DT, Markandu J, Sridharan V, Suganthan S (2000) Tetrahedron Lett 41:967–970CrossRefGoogle Scholar
  58. 58.
    Rinehart KL, Kobayashi J, Harbour GC, Hughes RG Jr, Mizsak SA, Scahill TA (1984) J Am Chem Soc 106:1524–1526CrossRefGoogle Scholar
  59. 59.
    Kobayashi J, Cheng JF, Ohta T, Nozoe S, Ohizumi Y, Sasaki T (1990) J Org Chem 55:3666–3670CrossRefGoogle Scholar
  60. 60.
    Scott JD, Williams RM (2002) Chem Rev 102:1669–1730CrossRefGoogle Scholar
  61. 61.
    Diness F, Meldal M (2010) Pept Sci 94:236–241CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of ChemistryCECBCopenhagenDenmark

Personalised recommendations