3,5-Dihalo-2(1H)-pyrazinones: Versatile Scaffolds in Organic Synthesis

Vijaykumar G. Pawar; Wim M. De Borggraeve

doi:10.1055/s-2006-942549

REVIEW

3,5-Dihalo-2(1H)-pyrazinones: Versatile Scaffolds in Organic Synthesis

Vijaykumar G. Pawar, Wim M. De Borggraeve*
Chemistry Department, Molecular Design and Synthesis, Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Fax: +32(16)327990; e-Mail: Wim.DeBorggraeve@chem.kuleuven.be;

Abstract

Alle Artikel dieser Rubrik

Abstract

3,5-Dihalo-2(1H)-pyrazinones have proven to be versatile scaffolds in organic synthesis. This review describes the methods to synthesise and functionalise these compounds. Applications of the 2(1H)-pyrazinone scaffold in peptide mimicry and drug design are discussed.

1 Introduction
2 Synthesis of 3,5-Dihalo-2(1H)-pyrazinones
3 Functionalisation of the Scaffold
3.1 Functionalisation at C³
3.2 Functionalisation at C⁵
3.3 Deblocking of N¹
3.4 Alkylation of N¹
4 Diels-Alder Reactions
4.1 Cycloaddition Reactions with Alkynes
4.2 Cycloaddition Reactions with Alkenes
5 Application of 2(1H)-Pyrazinones in Drug and Peptidomimetic Design
6 Solid-Phase Chemistry
7 Conclusion

Key words

pyrazinone - Diels-Alder reaction - nucleophilic aromatic substitution - cross-coupling reactions - peptidomimetic chemistry

Volltext

Referenzen

References

1 Norcross RD. Peterson I. Chem. Rev. 1995, 95: 2041

2 Faulkner DJ. Nat. Prod. Rep. 2002, 19: 1

3 Im HK. Im WB. Judge TM. Gammill RB. Hamilton BJ. Carter DB. Pregenzer JF. Mol. Pharmacol. 1993, 44: 468

4 Heeres J. de Jonge MR. Koymans LMH. Daeyaert FFD. Vinkers M. Van Aken KJA. Arnold E. Das K. Kilonda A. Hoornaert GJ. Compernolle F. Cegla M. Azzam RA. Andries K. de Bethune MP. Azijn H. Pauwels R. Lewi PJ. Janssen PAJ. J. Med. Chem. 2005, 48: 1910

5 Hirano K. Kubota T. Tsuda M. Watanabe K. Fromont J. Kobayashi Ji. Tetrahedron 2000, 56: 8107

6 Dunn G. Newbold GT. Spring FS. J. Chem Soc. 1949, 2586

7 Dutcher JD. J. Biol. Chem. 1947, 171: 321

8 Okada Y. Taguchi H. Yokoi T. Tetrahedron Lett. 1996, 37: 2249

9 Japp FR. Knox J. J. Chem. Soc. 1905, 87: 701

10 Tota YA. Elderfield RC. J. Org. Chem. 1942, 7: 313

11 Karmas G. Spoerri PE. J. Am. Chem. Soc. 1952, 74: 1580

12 Vekemans J. Pollers-Wieërs C. Hoornaert G. J. Heterocycl. Chem. 1983, 20: 919

13 De Borggraeve WM. Verbist BMP. Rombouts FJR. Pawar VG. Smets WJ. Kamoune L. Alen J. Van der Eycken EV. Compernolle F. Hoornaert GJ. Tetrahedron 2004, 60: 11597

14 Zhang X. Schmitt AC. Jiang W. Wasserman Z. Decicco CP. Bioorg. Med. Chem. Lett. 2003, 13: 1157

15 Janssen PAJ, Van Aken KJA, Lewi PJ, Koymans LMH, De Jonge MR, Heeres J, Daeyaert FFD, Hoornaert GJC, Compernolle FJC, and Kilonda A. inventors; WO 02078708. ; Chem. Abstr. 2002, 137, 294978

16 Loosen PK. Tutonda MG. Khorasani MF. Compernolle F. Hoornaert GJ. Tetrahedron 1991, 47: 9259

17 Hoornaert G. Bull. Soc. Chim. Belg. 1994, 103: 583

18 Azzam R. Ph.D. Thesis Katholieke Universiteit Leuven; Belgium: 2003.

19 Azzam R. De Borggraeve W. Compernolle F. Hoornaert GJ. Tetrahedron Lett. 2004, 45: 1885

20 Azzam R. De Borggraeve WM. Compernolle F. Hoornaert GJ. Tetrahedron 2005, 61: 3953

21 Kaval N. Bisztray K. Dehaen W. Kappe CO. Van der Eycken E. Mol. Divers. 2003, 7: 125

22 De Borggraeve WM. Appukkuttan P. Azzam R. Dehaen W. Compernolle F. Van der Eycken E. Hoornaert G. Synlett 2005, 777

23 Buysens K. Ph.D. Thesis Katholieke Universiteit Leuven; Belgium: 1996.

24 Buysens KJ. Vandenberghe DM. Hoornaert GJ. Tetrahedron 1996, 52: 9161

25 Vanchuyen N. Kurata T. Fujimaki M. Agric. Biol. Chem. 1973, 37: 327

26 Matsushita H. Lee S.-H. Yoshida K. Clapham B. Koch G. Zimmermann J. Janda KD. Org. Lett. 2004, 6: 4627

27 Rombouts F. Ph.D. Thesis Katholieke Universiteit Leuven; Belgium: 2002.

28 Rombouts FJR. De Borggraeve W. Toppet SM. Compernolle F. Hoornaert GJ. Tetrahedron Lett. 2001, 42: 7397

29 Rogiers J. De Borggraeve WM. Toppet SM. Compernolle F. Hoornaert GJ. Tetrahedron 2003, 59: 5047

30 Tutonda M. Vanderzande D. Hendrickx M. Hoornaert G. Tetrahedron 1990, 46: 5715

31 Tutonda M. Vanderzande D. Vekemans J. Toppet S. Hoornaert G. Tetrahedron Lett. 1986, 27: 2509

32 Tutonda MG. Vandenberghe SM. Van Aken KJ. Hoornaert GJ. J. Org. Chem. 1992, 57: 2935

33 Vandenberghe DM. Hoornaert GJ. Bull. Soc. Chim. Belg. 1994, 103: 185

34 Buysens KJ. Vandenberghe DM. Toppet SM. Hoornaert GJ. Tetrahedron 1995, 51: 12463

35 Buysens KJ. Vandenberghe DM. Toppet SM. Hoornaert GJ. J. Chem. Soc., Perkin Trans. 1 1996, 231

36 Loosen PK. Khorasani MF. Toppet SM. Hoornaert GJ. Tetrahedron 1991, 47: 9269

37 Vandenberghe SM. Buysens KJ. Meerpoel L. Loosen PK. Toppet SM. Hoornaert GJ. J. Org. Chem. 1996, 61: 304

38 Tahri A. Buysens KJ. Van der Eycken EV. Vandenberghe DM. Hoornaert GJ. Tetrahedron 1998, 54: 13211

39 Tahri A. De Borggraeve W. Buysens K. Van Meervelt L. Compernolle F. Hoornaert GJ. Tetrahedron 1999, 55: 14675

40 Rombouts FJR. Vanraes DAJ. Wynendaele J. Loosen PK. Luyten I. Toppet S. Compernolle F. Hoornaert GJ. Tetrahedron 2001, 57: 3209

41 De Borggraeve WM. Rombouts FJR. Verbist BMP. Van der Eycken EV. Hoornaert GJ. Tetrahedron Lett. 2002, 43: 447

42 Govaerts TC. Vogels IA. Compernolle F. Hoornaert GJ. Tetrahedron 2003, 59: 5481

43 Rombouts FJR. Van den Bossche J. Toppet SM. Compernolle F. Hoornaert GJ. Tetrahedron 2003, 59: 4721

44 Govaerts TC. Vogels IA. Compernolle F. Hoornaert GJ. Tetrahedron 2004, 60: 429

45 Rombouts FJR. De Borggraeve WM. Delaere D. Froeyen M. Toppet SM. Compernolle F. Hoornaert GJ. Eur. J. Org. Chem. 2003, 1868

46 Vandenberghe S. Ph.D. Thesis Katholieke Universiteit Leuven; Belgium: 1990.

47 Cappelle SL. Vogels IA. Govaerts TC. Toppet SM. Compernolle F. Hoornaert GJ. Tetrahedron 2002, 58: 3655

48 Govaerts TC. Vogels I. Compernolle F. Hoornaert G. Tetrahedron Lett. 2002, 43: 799

49 Kaval N. Ermolat"ev D. Appukkuttan P. Dehaen W. Kappe CO. Van der Eycken E. J. Comb. Chem. 2005, 7: 490

50 Hopkins C. Neuenschwander K. Scotese A. Jackson S. Nieduzak T. Pauls H. Liang G. Sides K. Cramer D. Cairns J. Maignan S. Mathieu M. Bioorg. Med. Chem. Lett. 2004, 14: 4819

51 Reiner JE. Siev DV. Araldi G.-L. Cui JJ. Ho JZ. Reddy KM. Mamedova L. Vu PH. Lee K.-SS. Minami NK. Gibson TS. Anderson SM. Bradbury AE. Nolan TG. Semple JE. Bioorg. Med. Chem. Lett. 2002, 12: 1203

52 Young MB. Barrow JC. Glass KL. Lundell GF. Newton CL. Pellicore JM. Rittle KE. Selnick HG. Stauffer KJ. Vacca JP. Williams PD. Bohn D. Clayton FC. Cook JJ. Krueger JA. Kuo LC. Lewis SD. Lucas BJ. McMasters DR. Miller-Stein C. Pietrak BL. Wallace AA. White RB. Wong B. Yan Y. Nantermet PG. J. Med. Chem. 2004, 47: 2995

53 South MS. Case BL. Wood RS. Jones DE. Hayes MJ. Girard TJ. Lachance RM. Nicholson NS. Clare M. Stevens AM. Stegeman RA. Stallings WC. Kurumbail RG. Parlow JJ. Bioorg. Med. Chem. Lett. 2003, 13: 2319

54 Han Y. Giroux A. Colucci J. Bayly CI. McKay DJ. Roy S. Xanthoudakis S. Vaillancourt J. Rasper DM. Tam J. Tawa P. Nicholson DW. Zamboni RJ. Bioorg. Med. Chem. Lett. 2005, 15: 1173

55 Miyazaki A. Tsuda Y. Tachibana Y. Yokoi T. Bryant SD. Lazarus LH. Keri G. Okada Y. Biopolymers 2003, 71: 367

56 Breslin MJ. Duggan ME. Halczenko W. Fernandez-Metzler C. Hunt CA. Leu CT. Merkle KM. Naylor-Olsen AM. Prueksaritanont T. Stump G. Wallace A. Rodan SB. Hutchinson JH. Bioorg. Med. Chem. Lett. 2003, 13: 1809

57 Breslin MJ. Halczenko W. Duggan ME. Gorham L. Fernandez-Metzler C. Hoffman WF. Hunt CA. Leu CT. Merkle K. Nagy R. Naylor-Olsen AM. Prueksaritanont T. Rodan S. Stump G. Wallace A. Hutchinson JH. Abstracts of Papers, 221st National Meeting of the American Chemical Society, San Diego, CA, April 1-5, 2001; American Chemical Society: Washington, DC, 2001, U46-U47

58 Boehner B, and Meyer W. inventors; US 4940482A. ; Chem. Abstr. 1991, 114, 42813

59 Parlow JJ. Case BL. Dice TA. Fenton RL. Hayes MJ. Jones DE. Neumann WL. Wood RS. Lachance RM. Girard TJ. Nicholson NS. Clare M. Stegeman RA. Stevens AM. Stallings WC. Kurumbail RG. South MS. J. Med. Chem. 2003, 46: 4050

60 Sanderson PE, Lyle TA, Dorsey BD, and Varsolona RJ. inventors; WO 9740024A1. ; Chem. Abstr. 1998, 128, 22922

61 Yaso M, Suzuki Y, Shibata K, and Hayashi E. inventors; JP 62198671A2. ; Chem. Abstr. 1988, 108, 167501

62 Arvanitis AG, Gilligan PJ, and Hartz RA. inventors; WO 2002092090A1. ; Chem. Abstr. 2002, 137, 370110

63 Arvanitis AG, Olson RE, Arnold CR, and Frietze WE. inventors; WO 9811075A1. ; Chem. Abstr. 1998, 128, 244063

64 Boys ML, Clare M, and Mitton-Fry MJ. inventors; WO 2005035527A1. ; Chem. Abstr. 2005, 142, 411378

65 Liang J, Chakravarty PK, Pan DE, Parsons WH, Shao PP, Ye F, and Zhou B. inventors; WO 2005097136A1. ; Chem. Abstr. 2005, 143, 387064

66 De Borggraeve WM. Rombouts FJR. Van der Eycken EV. Toppet SM. Hoornaert GJ. Tetrahedron Lett. 2001, 42: 5693

67 Pawar VG. De Borggraeve WM. Maes V. Tourwé DA. Compernolle F. Hoornaert GJ. Tetrahedron Lett. 2005, 46: 1707

68 Kamoune L. De Borggraeve WM. Verbist BMP. Vanden Broeck J. Coast GM. Compernolle F. Hoornaert G. Tetrahedron 2005, 61: 9555

69 Verbist BMP. De Borggraeve WM. Toppet S. Compernolle F. Hoornaert GJ. Eur. J. Org. Chem. 2005, 2941

70 Kaval N. Van der Eycken J. Caroen J. Dehaen W. Strohmeier GA. Kappe CO. Van der Eycken E. J. Comb. Chem. 2003, 5: 560

71 Kaval N. Dehaen W. Van der Eycken E. J. Comb. Chem. 2005, 7: 90