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Molecular Diversity

, Volume 16, Issue 3, pp 601–606 | Cite as

Synthesis of peptidomimetics, δ- and \({\varepsilon}\)-lactam tetrazoles

  • Steven Gunawan
  • Kristen Keck
  • Alex Laetsch
  • Christopher Hulme
Short Communication

Abstract

A concise two-step procedure for the synthesis of novel δ-lactam tetrazoles has been established via the Ugi-azide reaction using 5-oxohexanoic acid along with primary amines, isocyanides, and azidotrimethylsilane followed by 1,1′-carbonyldiimidazole-mediated intramolecular amide formation. Expansion to \({\varepsilon}\)-lactam tetrazole scaffolds was accomplished using methyl 6-oxoheptanoate via the same Ugi-azide reaction followed by basic hydrolysis and SOCl2 activation to enable lactam formation.

Keywords

Ugi reaction Multi-component reactions (MCRs) 1,5-disubstitutedtetrazoles 

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References

  1. 1.
    Zabrocki J, Smith GD, Dunbar JB Jr, Iijima H, Marshall GR (1988) Conformational mimicry. 1. 1,5-Disubstituted tetrazole ring as a surrogate for the cis amide bond. J Am Chem Soc 110: 5875–5880. doi: 10.1021/ja00225a045 CrossRefGoogle Scholar
  2. 2.
    Creighton CJ, Leo GC, Du W, Reitz AB (2004) Design, synthesis, and conformational analysis of eight-membered cyclic peptidomimetics prepared using ring closing metathesis. Bioorg Med Chem 12: 4375–4385. doi: 0.1016/j.bmc.2004.06.015 PubMedCrossRefGoogle Scholar
  3. 3.
    Kang SY, Lee S-H, Seo HJ, Jung ME, Ahn K, Kim J, Lee J (2008) Tetrazole-biarylpyrazole derivatives as cannabinoid CB1 receptor antagonists. Bioorg Med Chem Lett 18: 2385–2389. doi: 10.1016/j.bmcl.2008.02.061 PubMedCrossRefGoogle Scholar
  4. 4.
    Muraglia E, Kinzel OD, Laufer R, Miller MD, Moyer G, Munshi V, Orvieto F, Palumbi MC, Pescatore G, Rowley M, Williams PD, Summa V (2006) Tetrazolethioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant. Bioorg Med Chem Lett 16: 2748–2752. doi: 10.1016/j.bmcl.2006.02.024 PubMedCrossRefGoogle Scholar
  5. 5.
    O’Meara JA, Jakalian A, LaPlante S, Bonneau PR, Coulombe R, Faucher AM, Guse I, Landry S, Racine J, Simoneau B, Thavonekham B, Yoakim C (2007) Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse transcriptase inhibitors. Bioorg Med Chem Lett 17: 3336–3362. doi: 10.1016/j.bmcl.2007.03.097 Google Scholar
  6. 6.
    Al-Hourani BJ, Sharma SK, Mane JY, Tuszynski J, Baracos V, Kniess T, Suresh M, Pietzsch J, Wuest F (2011) Synthesis and evaluation of 1,5-diaryl-substituted tetrazoles as novel selective cyclooxygenase-2 (COX-2) inhibitors. Bioorg Med Chem Lett 21: 1823–1826. doi: 10.1016/j.bmcl.2011.01.057 PubMedCrossRefGoogle Scholar
  7. 7.
    Van Poecke S, Negri A, Janssens J, Solaroli N, Karlsson A, Gago F, Balzarini J, Van Calenbergh S (2011) Synthesis, modeling and evaluation of 3′-(1-aryl-1H-tetrazol-5-ylamino)-substituted 3′-deoxythymidine derivatives as potent and selective human mitochondrial thymidine kinase inhibitors. Org Biomol Chem 9: 892–901. doi: 10.1039/C0OB00591F PubMedCrossRefGoogle Scholar
  8. 8.
    Alexander JP, Cravatt BF (2006) The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases. J Am Chem Soc 128: 9699–9704. doi: 10.1021/ja062999h PubMedCrossRefGoogle Scholar
  9. 9.
    Hulme C, Tempest P, Ma V, Nixey T, Balow G (2005) PCT Int Appl, 260 pp. WO 2005019167.Google Scholar
  10. 10.
    Tempest P, Nixey T, Ma V, Balow G, van Staden C, Salon J, Rorer K, Baumgartner J, Hale C, Bannon T, Hungate R, Hulme C (2004) Novel potent tetrazole containing melanin concentrating hormone (MCH) receptor antagonists multi-component reactions lead the way. Abstract of Papers, 227th National Meeting of the American Chemical Society, Anaheim, CA: American Chemical Society: Washington, DC, 2004; MEDI 298Google Scholar
  11. 11.
    Nixey T, Boylan J, Hulme C, Powers D, Smith A, Wong A (2006) Inhibitors of the polo-like protein kinase Plk-1. Abstract of Papers, 231st National Meeting of the American Chemical Society, Atlanta, GA; American Chemical Society: Washington, DC, 2006; MEDI 277Google Scholar
  12. 12.
    Li J, Chen SY, Li JJ, Wang H, Hernandez AS, Tao S, Musial CM, Qu F, Swartz S, Chao ST, Flynn N, Murphy BJ, Slusarchyk DA, Seethala R, Yan M, Sleph P, Grover G, Smith MA, Beehler B, Giupponi L, Dickinson KE, Zhang H, Humphreys WG, Patel BP, Schwinden M, Stouch T, Cheng PTW, Biller SA, Ewing WR, Gordon D, Robl JA, Tino JA (2007) Discovery of a tetrazole-based growth hormone secretagogue: 4-(hydroxybutyl)carbamic acid 2-{5-[1-(2-amino-2-methylpropionylamino)-2-benzyloxyethyl]tetrazol-1-yl}ethyl ester (BMS-317180). J Med Chem 50: 5890–5893. doi: 10.1021/jm7010595 PubMedCrossRefGoogle Scholar
  13. 13.
    Hernández AS, Cheng PTW, Musial CM, Swartz SG, George RJ, Grover G, Slusarchyk D, Seethala RK, Smith M, Dickinson K, Giupponi L, Longhi DA, Flynn N, Murphy BJ, Gordon DA, Biller SA, Robl JA, Tino JA (2007) Discovery, synthesis, and structure–activity studies of tetrazole based growth hormone secretagogues. Bioorg Med Chem Lett 17: 5928–5933. doi: 10.1016/j.bmcl.2007.07.099 PubMedCrossRefGoogle Scholar
  14. 14.
    Ugi I (1962) The α-addition of immonium ions and anions to isonitriles accompanied by secondary reactions. Angew Chem Int Ed 1: 8–21. doi: 10.1002/anie.196200081 CrossRefGoogle Scholar
  15. 15.
    Nixey T, Kelly M, Hulme C (2000) The one-pot solution phase preparation of fused tetrazole-ketopiperazines. Tetrahedron Lett 41: 8729–8733. doi: 10.1016/S0040-4039(00)01563-X CrossRefGoogle Scholar
  16. 16.
    Domling A (2006) Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem Rev 106: 17–89. doi: 10.1021/cr0505728 PubMedCrossRefGoogle Scholar
  17. 17.
    Weber L (2000) High-diversity combinatorial libraries. Curr Opin Chem Biol 4: 295–302. doi: 10.1016/S1367-5931(00)00092-2 PubMedCrossRefGoogle Scholar
  18. 18.
    Hulme C, Gore V (2003) Multi-component reactions: emerging chemistry in drug discovery ‘From xylocain to crixivan’. Curr Med Chem 10: 51–80. doi: 10.2174/0929867033368600 PubMedCrossRefGoogle Scholar
  19. 19.
    Banfi L, Riva R, Basso A (2010) Coupling isocyanide-based multicomponent reactions with aliphatic or acyl nucleophilic substitution processes. Synlett 1: 23–41. doi: 10.1055/s-0029-1218527 CrossRefGoogle Scholar
  20. 20.
    Ilyn AP, Loseva MV, Vvedensky VY, Putsykina EB, Tkachenko SE, Kravchenko DV, Khvat AV, Krasavin MY, Ivachtchenko AV (2006) One-step assembly of carbamoyl-substituted heteroannelated [1,4]thiazepines. J Org Chem 71: 2811–2819. doi: 10.1021/jo052640w PubMedCrossRefGoogle Scholar
  21. 21.
    El Kaim L, Grimaud L (2009) Beyond the Ugi reaction: less conventional interactions between isocyanides and iminium species. Tetrahedron 65: 2153–2171. doi: 10.1016/j.tet.2008.12.002 CrossRefGoogle Scholar
  22. 22.
    Gunawan S, Petit J, Hulme C (2012) Concise one-pot preparation of unique bis-pyrrolidinone tetrazoles. ACS Comb Sci 14: 160–163. doi: 10.1021/co200209a PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Steven Gunawan
    • 1
  • Kristen Keck
    • 1
  • Alex Laetsch
    • 1
  • Christopher Hulme
    • 1
  1. 1.BIO5 Oro ValleyThe University of ArizonaOro ValleyUSA

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