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2005 | 3 | 2 | 288-294
Tytuł artykułu

Parallel synthesis of novel benzimidazoles on a soluble polymer support

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Liquid phase combinatorial synthesis using a soluble polyethylene glycol (PEG) polymer support and commercially available 3-nitro-4-fluoro benzoic acid is carried out in order to create a molecular library of trisubstituted benzimidazoles. The PEG-ester conjugate of 3-nitro-4-fluoro benzoic acid is subjected to ipso-fluoro displacement by various primary amines. The nitro group is reduced under neutral conditions using excess zinc and ammonium chloride, producing the polymer-boundo-phenylene diamines. Reaction of the diamines with different aldehydes results in cyclisation to benzimidazoles. The polymer support is cleaved releasing the desired products in high yields and purity. All reactions are performed at room temperature. [...]
Wydawca

Czasopismo
Rocznik
Tom
3
Numer
2
Strony
288-294
Opis fizyczny
Daty
wydano
2005-06-01
online
2005-06-01
Twórcy
  • Laboratory of Combinatorial Drug Discovery of Department of Chemistry, National Dong Hwa University, Shou-Feng, 974, Hualien, Taiwan
  • Laboratory of Combinatorial Drug Discovery of Department of Chemistry, National Dong Hwa University, Shou-Feng, 974, Hualien, Taiwan
  • Laboratory of Combinatorial Drug Discovery of Department of Chemistry, National Dong Hwa University, Shou-Feng, 974, Hualien, Taiwan, chungmingsun@yahoo.com
Bibliografia
  • [1] D.J. Gravert and K.D. Janda: “Organic synthesis on soluble polymer supports; Liquid phase methodologies”, Chem. Rev, Vol. 97, (1997), pp. 489–509. http://dx.doi.org/10.1021/cr960064l[Crossref]
  • [2] P.H.H. Hermkens, H.C.J. Ottenheijm and D.C. Rees: “Solid phase organic reactions II”, Tetrahedron, Vol. 53, (1997), pp. 5643–5678. http://dx.doi.org/10.1016/S0040-4020(97)00279-2[Crossref]
  • [3] C.M. Sun: “Recent advances in Liquid-Phase Combinatorial Chemistry”, Comb. Chem. High T. Scr., Vol. 3, (1999), pp. 299–318.
  • [4] C.M. Sun: “Soluble polymer supported synthesis of heterocyclic libraries”, In: L. Bellavance (Ed.): Combinatorial chemistry: Methods and Protocols in Molecular Biology Series, The Humana, New Jersey, (2002), Chapter 10, pp. 345–371.
  • [5] A.W. White, R. Almassy, A. Hillary-Clavert, N.J. Curtin, R.J. Griffin, Z. Hostomsky, K. Maegley, D.R. Newell, S. Srinivasan and B.T. Golding: “Resistance modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly (ADP-ribose) Polymerase”, J. Med. Chem, Vol. 43, (2000), pp. 4084–4097. http://dx.doi.org/10.1021/jm000950v[Crossref]
  • [6] G.J. Southan and C. Szabo: “Poly (ADP-ribose) Polymerase inhibitors”, Current. Med. Chem., Vol. 10, (2003), pp. 321–340.
  • [7] H. Goker, C. Kus, D.W. Boykin, S. Yildiz and M. Altanlar: “Synthesis of some new 2-substituted phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species”, Bioorg. Med. Chem. Lett., Vol. 10, (2002), pp. 2589–2596. http://dx.doi.org/10.1016/S0968-0896(02)00103-7[Crossref]
  • [8] S. Ozden, H. Ertepinar and O. Geban: “QSAR study on anti-bacterial effects of benzimidazole and imidazopyridine derivatives”, Collect. Czech. Commun., Vol. 60, (1995), pp. 2178–2188. http://dx.doi.org/10.1135/cccc19952178[Crossref]
  • [9] H. Goker, M. Tuncbilek, S. Suzen, C. Kus and N. Altanlar: “Synthesis and antimicrobial activity of some new 2-Phenyl-N-substituted carboxamido-1H-benzimidazole derivatives”, Arch. Pharm (Weinheim), Vol. 334, (2001), pp. 148–152. http://dx.doi.org/10.1002/1521-4184(200105)334:5<148::AID-ARDP148>3.0.CO;2-S[Crossref]
  • [10] T.E. Voogd, E.L.M. Vansterkenburg, J. Wilting and L.H. Janssen: “Recent research on the biological activity of Suramin”, Pharmacol. Rev., Vol. 45, (1993), pp. 177–203.
  • [11] A. Kreimeyer, G. Muller, M. Karsack, P. Nickeland and A.R.T. Gagliardi: “Suramine analogues with a 2-phenylbenzimidazole moiety as a partial structure: Potential HIV and Angiostatic drugs”, Arch. Pharm (Weinheim), Vol. 331, (1998), pp. 97–103. http://dx.doi.org/10.1002/(SICI)1521-4184(199803)331:3<97::AID-ARDP97>3.0.CO;2-F[Crossref]
  • [12] M. Pedini, G. Alunni-Bistocchi, A. Ricci, L. Bastianini and E. Lepri: “New heterocyclic derivatives of benzimidazole with germicidal activity”, Farmaco, Vol. 49, (1994), pp. 823–827.
  • [13] D. Tumelty, K. Cao and C.P. Holmes: “Traceless solid phase synthesis of substituted benzimidazoles via base-cleavable linker”, Org. Lett., Vol. 3, (2001), pp. 83–86. http://dx.doi.org/10.1021/ol006801o[Crossref]
  • [14] K.J. Lee and K.D. Janda: “Traceless solid-phase synthesis of 5-benzoylbenzimida-zoles”, Can. J. Chem., Vol. 79, (2001), pp. 1556–1561. http://dx.doi.org/10.1139/cjc-79-11-1556[Crossref]
  • [15] H. Akamatsu, K. Fukase and S. Kusumoto: “New efficient route for the solid phase synthesis of Benzimidazole derivatives”, J. Comb. Chem., Vol. 2, (2002), pp. 475–483. http://dx.doi.org/10.1021/cc020006f[Crossref]
  • [16] C.G. Blettner, W.A. Konig, G. Ruther, W. Stenzel and T. Schotten: “Paralell synthesis of poly (ethylene) glycol supported biaryl benzimidazoles and imidazopyridines”, Synlett., (1999), pp. 309–312.
  • [17] H. Matsushita, S.H. Lee, M. Joung, B. Clepham and K.D. Janda: “Smart cleavage reactions: the synthesis of benzimidazoles and benzothiazoles from polymer bound esters”, Tetrahedron Lett., Vol. 45, (2004), pp. 313–317. http://dx.doi.org/10.1016/j.tetlet.2003.10.168[Crossref]
  • [18] C.M. Yeh, C.L. Tung and C.M. Sun: “Combinatorial Liquid phase synthesis of Structurally Diverse Benzimidazole Libraries”, J. Comb. Chem., Vol. 2, (2000), pp. 341–348. http://dx.doi.org/10.1021/cc0000085[Crossref]
  • [19] Y.S. Su, M.J. Lin and C.M. Sun: “Mercury chloride assisted cyclisation towards benzimidazoles by focused microwave irradiation”, Tetrahedron Lett., Vol. 46, (2005), pp. 177–180. http://dx.doi.org/10.1016/j.tetlet.2004.10.170[Crossref]
  • [20] Y.C. Chi and C.M. Sun: “Soluble polymer supported synthesis of benzimidazole library”, Synlett., (2000), pp. 591–594.
  • [21] R. Jonas, M. Klockow, I. Lues, H. Prücher, H.J. Schliep and H. Wurziger: “Synthesis and biological activities of meribendan and related heterocyclic benzimidazolopyridaziones”, Eur. J. Med. Chem., Vol. 28, (1993), pp. 129–140. http://dx.doi.org/10.1016/0223-5234(93)90005-Y[Crossref]
  • [22] J.M. Smith and V. Krachňák: “A solid phase traceless synthesis of benzimidazoles with three combinatorial steps”, Tetrahedron. Lett., Vol. 40, (1999), pp. 7633–7636. http://dx.doi.org/10.1016/S0040-4039(99)01560-9[Crossref]
  • [23] P.L. Beaulieu, B. Haché and E. von Moos: “A Practical Oxone®-mediated, highthroughput, solution-phase synthesis of benzimidazolesfrom 1,2-phenylenediamines and aldehydes and its application to preparative scale synthesis”, Synthesis, (2003), pp. 1683–1692.
  • [24] A detailed experimental procedure for the first 3 steps of the sequence has been published in reference [18]. In a typical experiment, the polymer boundo-phenylene diamine 4 (500 mg) was stirred with three equivalents of an aldehyde (R2−CHO) in dichloromethane at room temperature for overnight. The solution was concentrated by rotary evaporation, and the reaction mixture was precipitated by addition of ether while stirring. The polymer-bound product was then filtered under aspirator pressure using a fritted funnel and washed several times with ethanol to obtain the precusor benzimidazole conjugates 5. The transesterification of the disubstituted benzimidazole in NaOMe/methanol is representative of the cleavage procedure: 540 mg of the benzimidazole-polymer conjugate was dissolved in 5 ml methanol containing 27 mg of sodium methoxide and stirred at room temperature for 3h. The solvent was evaporated under vacuum, and the polymer bound product was precipitated in ethanol. The polymer was filtered, and the combined filtrate was evaporated to give the crude product as pale yellow solid (35–43 mg, crude yield; 75–95%); The crude purity of the compounds was determined by HPLC analysis.1H-NMR spectral data (300 MHz, CDCl3) for 6c is as follows σ 8.52 (s, 1H); 8.00 (dd, J=8.7, 1.5 Hz, 1H); 7.67–7.63 (m, 3H); 7.54 (t, J=3.3 Hz, 3H); 4.87–4.79 (m, J=6.9 Hz, 1H); 3.96 (s, 3H); 1.66 (d, J=6.9 Hz, 6H).
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.-psjd-doi-10_2478_BF02475997
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