Photochemically Induced Synthesis of the Topoisomerase I Inhibitors Indeno[1,2-c]isoquinoline-5,11-diones

Abstract

A convenient synthesis of indeno[1,2-c]isoquinoline-5,11-diones has been achieved using combinational photochemical and carbocationic cyclization tactics. The synthetic route involved first the construction of adequately functionalized N-styryl benz­amides via Suzuki–Miyaura cross-coupling reaction with enol phosphate combined with a six-π-electron photocyclization process. The assembling of the title compounds was readily ensured through sequential carbocationic annulation reaction and ultimate oxidation of a latent hydroxy functionality.

Key words

enols - phosphates - cross-coupling - electrocyclic reactions - lactams

• References

• 1a Cushman M, Cheng L. J. Org. Chem. 1978; 43: 286
• 1b Cushman M, Cheng L. J. Org. Chem. 1978; 43: 3781
• 1c Kohlhagen G, Paull KD, Cushman M, Nagafuji P, Pommier Y. Mol. Pharmacol. 1998; 54: 50
• 2a Morrell A, Antony S, Kohlhagen G, Pommier Y, Cushman M. J. Med. Chem. 2006; 49: 7740
• 2b Nagarajan M, Morrell A, Ioanoviciu A, Antony S, Kohlhagen G, Agama KK, Hollingshead M, Pommier Y, Cushman M. J. Med. Chem. 2006; 49: 6283
• 3a Song Y, Shao Z, Dexheimer TS, Scher ES, Pommier Y, Cushman M. J. Med. Chem. 2010; 53: 1979
• 3b Ryckebusch A, Garcin D, Lansiaux A, Goossens J.-F, Baldeyrou B, Houssin R, Bailly C, Hénichart J.-P. J. Med. Chem. 2008; 51: 3617
• 3c Kim SH, Oh SM, Song JH, Cho D, Le QM, Lee S.-H, Cho W.-J, Kim TS. Bioorg. Med. Chem. 2008; 16: 1125
• 3d Van H TM, Le QM, Lee KY, Lee E.-S, Kwon Y, Kim TS, Le TN, Lee S.-H, Cho W.-J. Bioorg. Med. Chem. Lett. 2007; 17: 5763
• 3e Morrell A, Placzek M, Parmley S, Grella B, Antony S, Pommier Y, Cushman M. J. Med. Chem. 2007; 50: 4388
• 3f Morrell A, Placzek MS, Steffen JD, Antony S, Agama K, Pommier Y, Cushman M. J. Med. Chem. 2007; 50: 2040
• 3g Cho W.-J, Le QM, Hue Van H TM, Lee KY, Kang BY, Lee E.-S, Lee SK, Kwon Y. Bioorg. Med. Chem. Lett. 2007; 17: 3531
• 3h Pommier Y, Cushman M. Mol. Cancer Ther. 2009; 8: 1008
• 3i Cinelli MA, Morrell A, Dexheimer TS, Scher ES, Pommier Y, Cushman M. J. Med. Chem. 2008; 51: 4609
• 4a Nagarajan M, Morrell A, Antony S, Kohlhagen G, Agama K, Pommier Y, Ragazzon PA, Garbett NC, Chaires JB, Hollingshead M, Cushman M. J. Med. Chem. 2006; 49: 5129
• 4b Morrell A, Placzek M, Parmley S, Antony S, Dexheimer TS, Pommier Y, Cushman M. J. Med. Chem. 2007; 50: 4419
• 5a Morrell A, Antony S, Kohlhagen G, Pommier Y, Cushman M. Bioorg. Med. Chem. Lett. 2006; 16: 1846
• 5b Xiao X, Antony S, Kohlhagen G, Pommier Y, Cushman M. Bioorg. Med. Chem. 2004; 12: 5147
• 5c Nagarajan M, Xiao X, Antony S, Kohlhagen G, Pommier Y, Cushman M. J. Med. Chem. 2003; 46: 5712
• 5d Nagarajan M, Morrell A, Fort BC, Meckley MR, Antony S, Kohlhagen G, Pommier Y, Cushman M. J. Med. Chem. 2004; 47: 5651
• 6a Pommier Y, Pourquier P, Fan Y, Strumberg D. Biochem. Biophys. Acta 1998; 1400: 83
• 6b Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr., Stewart L. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 15387
• 6c Antony S, Jayaraman M, Laco G, Kohlhagen G, Kohn KW, Cushman M, Pommier Y. Cancer Res. 2003; 63: 7428
• 6d Antony S, Kohlhagen G, Agama K, Jayaraman M, Cao S, Durrani FA, Rustum YM, Cushman M, Pommier Y. Mol. Pharmacol. 2005; 67: 523
• 6e Staker BL, Feese MD, Cushman M, Pommier Y, Zembower D, Stewart L, Burgin AB. J. Med. Chem. 2005; 48: 2336
• 6f Ioanoviciu A, Antony S, Pommier Y, Staker BL, Stewart L, Cushman M. J. Med. Chem. 2005; 48: 4803
• 7 Pommier Y. Nat. Rev. Cancer 2006; 6: 789
• 8 Peterson KE, Cinelli MA, Morrell AE, Mehta A, Dexheimer TS, Agama K, Antony S, Pommier Y, Cushman M. J. Med. Chem. 2011; 54: 4937
• 9 Strumberg D, Pommier Y, Paull K, Jayaraman M, Nagafuji P, Cushman M. J. Med. Chem. 1999; 42: 446
• 10a Antony S, Agama KK, Miao Z.-H, Takagi K, Wright MH, Robles AI, Varticovski L, Nagarajan M, Morrell A, Cushman M, Pommier Y. Cancer Res. 2007; 67: 10397
• 10b Xiao X, Cushman M. J. Org. Chem. 2005; 70: 6496
• 11 Lebrun S, Couture A, Deniau E, Grandclaudon P. Tetrahedron Lett. 2011; 52: 1481
• 12a Gonzalez-Lopez M, Shaw TJ. Chem. Rev. 2009; 109: 164
• 12b Vara Y, Bello T, Aldaba E, Arrieta A, Pizarro JL, Arriortua MI, Lopez X, Cossío FP. Org. Lett. 2008; 10: 4759
• 13a Ninomiya I, Naito TMori T. J. Chem. Soc., Perkin Trans. 1 1973; 505
• 13b Lenz GR. J. Org. Chem. 1974; 39: 2839
• 13c Lenz GR. J. Org. Chem. 1976; 41: 2201
• 13d Ninomiya I, Shinohara A, Kiguchi T, Naito T. J. Chem. Soc., Perkin Trans. 1 1976; 1896
• 13e Ninomiya I, Yamamoto O, Kiguchi T, Naito T, Ishii H. Heterocycles 1977; 6: 1730
• 13f Kametani T, Sugai T, Shoji Y, Honda T, Satoh F, Fukumoto K. J. Chem. Soc., Perkin Trans. 1 1977; 1151
• 13g Ninomiya I, Naito T. Heterocycles 1981; 15: 1433
• 13h Mallory FB, Mallory CW. Org. React. 1984; 30: 1
• 13i Couture A, Grandclaudon P. Synthesis 1986; 576
• 13j Rigby JH, Gupta V. Synlett 1995; 547
• 13k Couture A, Grandclaudon P, Hooijer SO. J. Org. Chem. 1991; 56: 4977
• 13l Grese TA, Adrian MD, Phillips DL, Shetler PK, Short LL, Glasebrook AL, Bryant HU. J. Med. Chem. 2001; 44: 2857

• See, among others:

• 14a Bouet A, Cieslikiewicz M, Lewinski K, Coudert G, Gillaizeau I. Tetrahedron 2010; 66: 498
• 14b Steel PG, Woods TM. Synthesis 2009; 3897
• 14c Fuwa H, Sasaki M. Org. Lett. 2007; 9: 3347
• 14d Claveau E, Gillaizeau I, Blu J, Bruel A, Coudert G. J. Org. Chem. 2007; 72: 4832
• 14e Hansen AL, Ebran J.-P, Gogsig TM, Skrydstrup T. J. Org. Chem. 2007; 72: 6464
• 14f Occhiato EG, Lo Galbo F, Guarna A. J. Org. Chem. 2005; 70: 7324
• 14g Lepifre F, Clavier S, Bouyssou P, Coudert G. Tetrahedron 2001; 57: 6969
• 15 Naumov MI, Sutirin SA, Shavyrin AS, Ganina OG, Beletskaya IP, Bourgarel-Rey V, Combes S, Finet J.-P, Fedorov AY. J. Org. Chem. 2007; 72: 3293
• 16a Mori K, Ohmori K, Suzuki K. Angew. Chem. Int. Ed. 2009; 48: 5633
• 16b Mohri S.-I, Stefinovic M, Snieckus V. J. Org. Chem. 1997; 62: 7072
• 16c Nicolaou KC, Ramanjulu JM, Natarajan S, Bräse S, Rübsam F. Chem. Commun. 1997; 1899
• 17 N-Benzyl-N-[1-(2-hydroxymethylphenyl)vinyl]-2-methoxybenzamide (2a): pale yellow solid; mp 147–148 °C. ¹H NMR (300 MHz, C₆D₆): δ = 1.82 (br s, 1 H), 3.21 (s, 3 H), 4.33 (d, J = 11.7 Hz, 1 H), 4.73 (br s, 1 H), 5.16 (br s, 2 H), 6.30 (br s, 1 H), 6.64 (br s, 1 H), 6.82–7.34 (m, 10 H), 7.36–7.64 (m, 3 H) ppm. ¹³C NMR (75 MHz, C₆D₆): δ = 52.6, 54.8, 62.3, 110.8, 112.3, 120.2, 121.4, 125.3, 127.4 (2 × CH), 128.5 (2 × CH), 128.7, 129.7, 129.9, 130.1, 132.6, 133.1, 137.4, 139.7, 140.5, 155.9, 169.5 ppm. Anal. Calcd for C₂₄H₂₃NO₃: C, 77.19; H, 6.21; N, 3.75. Found: C, 77.02; H, 5.94; N, 3.97
• 18a Ninomiya I, Kiguchi T, Yamamoto O, Naito T. J. Chem. Soc., Perkin Trans. 1 1979; 1723
• 18b Lenz GR. Tetrahedron Lett. 1973; 22: 1963
• 19 2-Benzyl-3-(2-hydroxymethylphenyl)-2H-isoquinolin-1-one (3a): yellow crystals; mp 102–103 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.62 (br s, 1 H), 4.00 (d, J = 13.3 Hz, 1 H), 4.30 (d, J = 13.3 Hz, 1 H), 4.94 (d, J = 14.8 Hz, 1 H), 5.45 (d, J = 14.8 Hz, 1 H), 6.39 (s, 1 H), 6.83 (d, J = 6.6 Hz, 2 H), 7.12–7.22 (m, 4 H), 7.32 (t, J = 7.3 Hz, 1 H), 7.42–7.61 (m, 4 H), 7.70 (t, J = 7.5 Hz, 1 H), 8.55 (d, J = 8.0 Hz, 1 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 48.2, 62.3, 108.1, 125.3, 125.9, 126.9, 127.1, 127.2, 127.6 (2 × CH), 127.7, 128.3, 128.4 (2 × CH), 129.6, 129.7, 132.6, 133.4, 136.2, 137.5, 140.0, 141.1, 163.3 ppm. Anal. Calcd for C₂₃H₁₉NO₂: C, 80.92; H, 5.61; N, 4.10. Found: C, 80.72; H, 5.84; N, 3.85
• 20a Jagtap PG, Baloglu E, Southan GJ, Mabley JG, Li H, Zhou J, van Duzer J, Salzman AL, Szabó C. J. Med. Chem. 2005; 48: 5100
• 20b Wsol V, Szotakova B, Skalova L, Maser E. Toxicology 2004; 197: 253
• 20c Wsol V, Szotakova B, Martin H.-J, Maser E. Toxicology 2007; 238: 111
• 20d Novotna R, Wsol V, Xiong G, Maser E. Toxicology Lett. 2008; 181: 1
• 21 For compound 1a (mp 211–212 °C; lit. 202–205 °C), see: Wawzonek S. Org. Prep. Proced. Int. 1982; 14: 16