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DOI: 10.1055/s-0029-1217049
A Convenient Procedure for the Synthesis of New α-Pyridinyl-Substituted 7H-Indeno[2,1-c]quinoline Derivatives Based on a Three-Component Imino Diels-Alder Reaction
Publication History
Publication Date:
19 October 2009 (online)
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Abstract
A new series of α-pyridinyl-substituted indeno[2,1-c]quinoline derivatives was prepared with good yields according to a two-step synthesis. The first and key step involves the formation of the ring via three-component imino Diels-Alder cycloaddition between an aniline, pyridine-2-carbaldehyde, and indene using boron trifluoride-diethyl ether complex as a catalyst to produce the corresponding 5,6,6a,11b-tetrahydroindeno[2,1-c]quinolines. The second step consisted of their oxidation with powdered sulfur to obtain the corresponding indeno[2,1-c]quinolines, analogues of DNA topoisomerase inhibitor TAS-103.
Key words
cycloaddition - multicomponent reaction - imino Diels-Alder reaction - indeno[2,1-c]quinolines
-
1a
Kouznetsov V.Palma A.Ewert C.Varlamov A. J. Heterocycl. Chem. 1998, 35: 761 -
1b
Katritzky AR.Rachwal S.Rachwal B. Tetrahedron 1996, 52: 15031 -
1c
Carling RW.Leeson PD.Moseley AM.Baker R.Forster AC.Grimwood S.Kemp JA.Marshall GR. J. Med. Chem. 1992, 35: 1942 -
1d
Cai SX.Zhou Z.-L.Huang J.-C.Whittermore ER.Egbuwoku ZO.Lü Y.Hawkinson JE.Woodward RM.Keana JFW. J. Med. Chem. 1996, 39: 3248 -
2a
Bendale P.Olepu S.Kumar SP.Buldule V.Rivas K.Nallan L.Smart B.Yokoyama K.Ankala S.Rao PP.Floyd D.Lombardo L.Williams DK.Buckner FS.Chakrabarti D.Verlinde CMJ.Van Voorhis WC.Gelb MH. J. Med. Chem. 2007, 50: 4585 -
2b
Jacquemond-Collet I.Benoit-Vical F.Valentin A.Stanislas E.Mallie M.Fouraste I. Planta Med. 2002, 68: 68 -
3a
Nishiyama TT.Hashiguchi YY.Sakata ST.Sakaguchi TT. Polym. Degrad. Stab. 2003, 79: 225 -
3b
Dorey G.Lockhart B.Lestage P.Casara P. Bioorg. Med. Chem. Lett. 2000, 10: 9350 - 4
Calhoun W.Carlson RP.Crossley R.Datko LJ.Dietrich S.Heatherington K.Marshall LA.Meade PJ.Opalko A.Shepherd RG. J. Med. Chem. 1995, 38: 1473 -
5a
Gelderblom H.Sparreboom A. In Drugs Affecting Growth of TumoursPinedo HM.Smorenburg CH. Birkhauser Verlag; Switzerland: 2006. p.83 -
5b
Denny WA.Baguley BC. Curr. Top. Med. Chem. 2003, 3: 339 -
6a
Pommier Y. Nat. Rev. Cancer 2006, 6: 789 -
6b
Priel E.Showalter SD.Roberts M.Oroszlan S.Blair DG. J. Virol. 1991, 65: 4137 -
6c
Herben VMM.ten Bokkel HWW.Schellens JHM.Beijnen JH. Pharm. World Sci. 1998, 20: 161 -
7a
Li Q.-Y.Zu Y.-G.Shi R.-Z.Yao L.-P. Curr. Med. Chem. 2006, 13: 2021 -
7b
Martínez R.Chacón-García L. Curr. Med. Chem. 2005, 12: 127 -
7c
Liew ST.Yang LX. Curr. Pharm. Des. 2008, 14: 1078 -
7d
Yount G.Yang Y.Wong B.Wang HJ.Yang LX. Anticancer Res. 2007, 27: 3173 -
8a
Denny WA.Baguley BC. Curr. Top. Med. Chem. 2003, 3: 339 -
8b
Minderman H.Wrzosek C.Cao S.-S.Utsugi T.Kobunai T.Yamada Y.Rustum YM. Cancer Chemother. Pharmacol. 2000, 45: 78 -
9a
Twelves CJ.Gardner C.Flavin A.Sludden J.Dennis I.de Bono J.Beale P.Vasey P.Hutchison C.Macham MA.Rodríguez A.Judson I.Bleehen NM. Br. J. Cancer 1999, 80: 1786 -
9b
Ohyama T.Li Y.Utsugi T.Irie S.Yamada Y.Sato T. Jpn. J. Cancer Res. 1999, 44: 691 -
10a
Ewesuedo RB.Iyer L.Das S.Koenig A.Mani S.Vogelzang NJ.Schilsky RL.Brenckman W.Ratain MJ. J. Clin. Oncol. 2001, 19: 2084 -
10b
Ishida K.Asao T. Biochim. Biophys. Acta 2002, 1587: 155 -
10c
Osman S.Luthra SK.Brady F.Hume SP.Brown G.Harte RJA.Matthews JC.Denny WA.Baguley BC.Jones T.Price PM. Cancer Res. 1997, 57: 2172 -
10d
Dittrich C.Dieras V.Kerbrat P.Punt C.Sorio R.Copanigro F.Paoletti X.Balincourt C.Lacombe D.Fumoleau P. Invest. New Drugs 2003, 21: 347 -
11a
Anzini M.Cappelli A.Vomero S. J. Heterocycl. Chem. 1991, 28: 1809 -
11b
Cappelli A.Anzini M.Vomero S.Canullo L.Mennuni L.Makovec F.Doucet E.Hamon M.Menziani MC.De Benedetti PG.Bruni G.Romeo MR.Giorgi G.Donati A. J. Med. Chem. 1999, 42: 1556 -
12a
Kouznetsov VV.Romero BAR.Stashenko EE. Tetrahedron Lett. 2007, 48: 8855 -
12b
Sridharan V.Perumal PT.Avendaño PC.Menéndez JC. Org. Biomol. Chem. 2007, 5: 1351 -
12c
Akiyama T.Morita H.Fuchibe K. J. Am. Chem. Soc. 2006, 128: 13070 -
12d
Legros J.Crousse B.Qurévitch M.Bonnet-Delpon D. Synlett 2006, 1899 -
12e
Akiyama T.Nakashima S.Yokota K.Fuchibe K. Chem. Lett. 2004, 33: 922 - For a recent review of imino Diels-Alder reactions, see:
-
13a
Kouznetsov VV. Tetrahedron 2009, 65: 2721 -
13b
Glushkov VA.Tolstikov AG. Russ. Chem. Rev. (Engl. Transl.) 2008, 77: 137 -
13c
Olsen J.-C.Oh T. Tetrahedron 2001, 57: 6099 - 14
Subba Reddy BV.Srinivas R.Yadav JS.Ramalingam T. Synth. Commun. 2001, 31: 1075 - 15
Babu G.Perumal PT. Tetrahedron Lett. 1998, 39: 3225 - 16
Kobayashi S.Ishitani H.Nagayama S. Synthesis 1995, 1195 - 17
Yadav JS.Subba Reddy BV.Srinivas R.Madhuri Ch.Ramalingam T. Synlett 2001, 240 - 18
Kobayashi S.Nagayama S. J. Am. Chem. Soc. 1996, 118: 8977 -
19a
Kiselyov A.Smith L.Armstrong R. Tetrahedron 1998, 54: 5089 -
19b
Kiselyov A.Smith L.Virgilio A.Armstrong R. Tetrahedron 1998, 54: 7987 - 20
Kouznetsov VV.Ochoa Puentes C.Zachinno SA.Gupta M.Romero BAR.Sortino M.Vásquez Y.Bahsas A.Amaro-Luis J. Lett. Org. Chem. 2006, 3: 300 -
21a
Vargas MLY.Castelli MV.Kouznetsov VV.Urbina GJM.López SN.Sortino M.Enriz RD.Ribas JC.Zacchino SA. Bioorg. Med. Chem. 2003, 11: 1531 -
21b
Kouznetsov VV.Rivero Castro J.Ochoa Puentes C.Stashenko EE.René Martinez J.Ochoa C.Montoro Pereira D.Nogal Ruiz JJ.Fernández Portillo C.Muelas Serrano S.Gómez Barrio A.Bahsas A.Amaro-Luis J. Arch. Pharm. (Weinheim, Ger.) 2005, 338: 32 -
21c
Kouznetsov VV.Zubkov FI.Mora U.Nikitina EV. Synthesis 2007, 375
References
Full crystallographic data for indenoquinoline 7c will be published elsewhere.
23Another commonly used oxidant, DDQ in MeCN, was less efficient for this process due poor solubility of the starting tetrahydroindeno[2,1-c]quinolines.
24Antitumoral and cytotoxic activities for this new series of compounds will be published in due course.