Preparation of Reduced Pyrazino[2,1-a]isoquinoline Derivatives: Important Heterocycles in the Field of Bioactive Compounds

Abstract

Partially hydrogenated pyrazino[2,1-a]isoquinoline derivatives, such as praziquantel, have been the subject of significant research efforts in the field of medicinal chemistry, thanks to their antihelmintic, antiprotozoal, and antifungal activities. Nevertheless, methods for their efficient synthesis (and especially for their stereoselective preparation) can be traced back to just a few general procedures. In this short review we will summarize the approaches developed so far to access pyrazino[2,1-a]isoquinolines, with a particular focus on bioactive derivatives, and will highlight their features and weaknesses, aiming to stimulate further investigations in the preparation of this important class of heterocyclic compounds.

1 Introduction

2 Different Approaches to the Synthesis of Pyrazino[2,1-a]isoquinolines

2.1 1-(Aminomethyl)tetrahydroisoquinoline Ring Closure

2.2 Diketopiperazine Reduction/Cyclization

2.3 N-Acyliminium Ion Cyclizations

2.4 Radical Cyclizations

2.5 Multicomponent Reactions

2.6 Miscellaneous Routes

3 Access to Enantiomerically Pure Praziquantel

4 Conclusions

Key words

pyrazino[2,1-a]isoquinoline - organic synthesis - heterocyclic chemistry - medicinal chemistry - praziquantel

• References

• 1 Galloway WR. J. D, Isidro-Llobet A, Spring DR. Nat. Commun. 2010; 1: 80
• 2 Dömling A, Khoury K. ChemMedChem 2010; 5: 1420
• 3 Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, Savioli L. N. Engl. J. Med. 2007; 357: 1018
• 4 Fact sheet from the World Health Organization: http://www.who.int/mediacentre/factsheets/fs115/en/.
• 5 See, for example, the program coordinated by the Schistosomiasis Control Initiative: http://www3.imperial.ac.uk/schisto.
• 6 Caffrey CR. Curr. Opin. Chem. Biol. 2007; 11: 433
• 7 Seubert J, Pohlke R, Loebich F. Experientia 1977; 33: 1036
• 8a Van Dyke JW. J, Havera HJ, Johnson RD, Vidrio H, Viveros A. J. Med. Chem. 1972; 15: 91
• 8b Ward TJ, White JF, Lattimer N, Rhodes KF, Sharma S, Waterfall JF. J. Med. Chem. 1988; 31: 1421
• 8c Clark RD, Repke DB, Kilpatrick AT, Brown CM, MacKinnon AC, Clague RU, Spedding M. J. Med. Chem. 1989; 32: 2034
• 9 Maryanoff BE, McComsey DF, Taylor RJ. J, Gardocki JF. J. Med. Chem. 1981; 24: 79
• 10 Lubbers T, Bohringer M, Gobbi L, Hennig M, Hunziker D, Kuhn B, Loffler B, Mattei P, Narquizion R, Peters J.-U, Ruff Y, Wessel HP, Wyss P. Bioorg. Med. Chem. Lett. 2007; 17: 2966
• 11 Thesing J, Seitz G, Pohlke R, Sommer S, Müller-Calgan H, Götz M. BE 659249, 1965 ; Chem. Abstr. 1965, 64, 11554.
• 12 Wenner W, Stefaniw M. J. Heterocycl. Chem. 1967; 4: 469
• 13 Van der Burg WJ, Bonta IL, Delobelle J, Ramon C, Vargaftig B. J. Med. Chem. 1970; 13: 35
• 14 Seubert J, Thomas H, Andrews P. DE 2362539, 1975 ; Chem. Abstr. 1976, 84, 5007b.
• 15a Pohlke R, Loebich F, Seubert J, Thomas H, Andrews P. DE 2331713, 1975 ; Chem. Abstr. 1975, 82, 156369.
• 15b Pohlke R, Loebich F, Thomas H, Thysen J. DE 2312134, 1974 ; Chem. Abstr. 1975, 82, 129275.
• 15c Seubert J. DE 2418111, 1975 ; Chem. Abstr. 1976, 84, 44156.
• 15d Seubert J, Pohlke R, Thomas H, Andrews P. DE 2441261, 1976 ; Chem. Abstr. 1976, 85, 5687.
• 15e Seubert J. DE 2504250, 1976 ; Chem. Abstr. 1976, 85, 142999.
• 15f Seubert J. DE 2457971, 1976 ; Chem. Abstr. 1976, 85, 160160.
• 15g Pohlke R. DE 2508947, 1976 ; Chem. Abstr. 1976, 86, 16705.
• 15h Pohlke R. DE 1795728, 1977 ; Chem. Abstr. 1977, 87, 168092.
• 16 Kiec-Kononowicz K, Farghaly ZS, Blaschke G. Arch. Pharm. (Weinheim) 1991; 324: 235
• 17 Sadhu PS, Kumar SN, Chandrasekharam M, Pica-Mattoccia L, Cioli D, Rao VJ. Bioorg. Med. Chem. Lett. 2012; 22: 1103
• 18 Shekhter OV, Sergovskaya NL, Tsizin YS. Chem. Heterocycl. Comp. (USSR) 1985; 21: 665
• 19 Griffith RC, Gentile RJ, Robichaud RC, Frankenheim J. J. Med. Chem. 1984; 27: 995
• 20 Tsang AS.-K, Ingram K, Keiser J, Brynn Hibbert D, Todd MH. Org. Biomol. Chem. 2013; 11: 4921
• 21 Dhanasekaran S, Suneja A, Bisai V, Singh VK. Org. Lett. 2016; 18: 634
• 22 Rahman A.-u, Ghazala N, Sultana N, Bashir M. Tetrahedron Lett. 1980; 21: 1773
• 23 Frehel D, Maffrand J.-P. Heterocycles 1983; 20: 1731
• 24 Yuste F, Pallás Y, Barrios H, Ortíz B, Sánchez-Obregón R. J. Heterocycl. Chem. 1986; 23: 189
• 25 Brewer MD, Burgess MN, Dorgan RJ. J, Elliott RL, Mamalis P, Manger BR, Webster RA. B. J. Med. Chem. 1989; 32: 2058
• 26 Hudack RA. Jr, Barta NS, Guo C, Deal J, Dong L, Fay LK, Caprathe B, Chatterjee A, Vanderpool D, Bigge C, Showalter R, Bender S, Augelli-Szafran CE, Lunney E, Hou X. J. Med. Chem. 2006; 49: 1202
• 27 Krejcarek GA, Dominy BW, Lawton RG. Chem. Commun. 1968; 1450
• 28 Speckamp WN, Hiemstra H. Tetrahedron 1985; 41: 4367
• 29 Kim JH, Lee YS, Park H, Kim CS. Tetrahedron 1998; 54: 7395
• 30 Kim JH, Lee YS, Kim CS. Heterocycles 1998; 48: 2279
• 31 Jiang Z. CN 101,445,507, 2009 ; Chem. Abstr. 2009, 151, 78143.
• 32 Kim CS, Min DY. Arch. Pharmacal Res. 1998; 21: 744
• 33a Tang H, Zheng C, Lv J, Wu J, Li Y, Yang H, Fu B, Li C, Zhou Y, Zhu J. Bioorg. Med. Chem. Lett. 2010; 20: 979
• 33b Tang H, Zheng C, Zhu J, Fu B, Zhou Y, Lv J. Arch. Pharm. Chem. Life Sci. 2010; 343: 360
• 34 Seki M, Ogiku T. Tetrahedron 2014; 70: 3864
• 35 Zawadzka A, Leniewski A, Maurin JK, Wojtasiewicz K, Czarnocki Z. Org. Lett. 2001; 3: 997
• 36 Zawadzka A, Leniewski A, Maurin JK, Wojtasiewicz K, Siwicka A, Blachut D, Czarnocki Z. Eur. J. Org. Chem. 2003; 2443
• 37 Siwicka A, Wojtasiewicz K, Rosiek B, Leniewski A, Maurin JK, Czarnocki Z. Tetrahedron: Asymmetry 2005; 16: 975
• 38 Kölzer M, Weitzel K, Göringer HU, Thines E, Opatz T. ChemMedChem 2010; 5: 1456
• 39 Wink M, Schmeller T, Latz-Bruning B. J. Chem. Ecol. 1998; 24: 1881
• 40 Samuelson J, Ayala P, Orozco E, Wirth D. Mol. Biochem. Parasitol. 1990; 38: 281
• 41 El-Fayyoumy S, Mansour W, Todd MH. Tetrahedron Lett. 2006; 47: 1287
• 42 Petersen R, Le Quement ST, Nielsen TE. Angew. Chem. Int. Ed. 2014; 53: 11778
• 43 Todd MH, Ndubaku C, Bartlett PA. J. Org. Chem. 2002; 67: 3985
• 44a Reginato G, Di Credico B, Andreotti D, Mingardi A, Paio A, Donati D, Pezzati B, Mordini A. Tetrahedron: Asymmetry 2010; 21: 191
• 44b Mordini A, Reginato G, Calamante M, Zani L. Curr. Top. Med. Chem. 2014; 14: 1308
• 45 Reginato G, Di Credico B, Andreotti D, Paio A, Donati D. Tetrahedron: Asymmetry 2007; 18: 2680
• 46 Reginato G, Catalani MP, Pezzati B, Di Fabio R, Bernardelli A, Curcuruto O, Moro E, Pozzan A, Mordini A. Org. Lett. 2015; 17: 398
• 47 For a review, see: Dömling A. Chem. Rev. 2006; 106: 17
• 48 El Kaim L, Gageat M, Gaultier L, Grimaud L. Synlett 2007; 500
• 49 Köhler V, Bailey KR, Znabet A, Raftery J, Helliwell M, Turner NJ. Angew. Chem. Int. Ed. 2010; 49: 5289
• 50 Znabet A, Zonneveld J, Janssen E, De Kanter FJ. J, Helliwell M, Turner NJ, Ruijter E, Orru RV. A. Chem. Commun. 2010; 46: 7706
• 51 Cao H, Liu H, Dömling A. Chem. Eur. J. 2010; 16: 12296
• 52 Liu H, William S, Herdtweck E, Botros S, Dömling A. Chem. Biol. Drug Des. 2012; 79: 470
• 53 Wang Z.-x, Chen J.-l, Qiao C. Chem. Biol. Drug Des. 2013; 82: 216
• 54 Wang W, Ollio S, Herdtweck H, Dömling A. J. Org. Chem. 2011; 76: 637
• 55 Patil P, Khoury K, Herdtweck H, Dömling A. Bioorg. Med. Chem. 2015; 23: 2699
• 56 Neochoritis CG, Zarganes-Tzitzikas T, Stotani S, Dömling A, Herdtweck H, Khoury K, Dömling A. ACS Comb. Sci. 2015; 17: 493
• 57 Khan I, Khan S, Tyagi V, Chouhan PS, Chauan PM. S. RSC Adv. 2015; 5: 102713
• 58 Berkowitz WF, John TV. J. Org. Chem. 1984; 49: 5269
• 59 Novaes MR. C. G, de Souza JP, de Araújo HC. Quim. Nova 1999; 22: 5
• 60a Xiao SH, Catto BA. J. Infect. Dis. 1989; 159: 589
• 60b Tanaka M, Ohmae H, Utsonomiya H, Nara T, Irie Y, Yasuraoka K. Am. J. Trop. Med. Hyg. 1989; 41: 198
• 61 Wu MH, Wei CC, Xu ZY, Yuan HC, Lian WN, Yang Q.-J, Chen M, Jiang Q.-W, Wang C.-Z, Zhang S.-J, Liu Z.-D, Wei R.-M, Yuan S.-J, Hu L.-S, Wu Z.-S. Am. J. Trop. Med. Hyg. 1991; 45: 345
• 62 Meyer T, Sekljic H, Fuchs S, Bothe H, Schollmeyer D, Miculka C. PLoS Neglected Trop. Dis. 2009; 3: e357
• 63 Chromatographic resolution of praziquantel using a chiral stationary phase was reported: Blaschke G. J. Liq. Chromatogr. 1986; 9: 341
• 64 Laurent SA.-L, Boissier J, Coslédan F, Gornitzka H, Robert A, Meunier B. Eur. J. Org. Chem. 2008; 895
• 65 Cedillo-Cruz A, Aguilar MI, Flores-Alamo M, Palomares-Alonso F, Jung-Cook H. Tetrahedron: Asymmetry 2014; 25: 133
• 66 Woelfle M, Seerden J.-P, de Gooijer J, Pouwer K, Olliaro P, Todd MH. PLoS Neglected Trop. Dis. 2011; 5: e1260
• 67 Ma C, Zhang Q.-F, Tan Y.-B, Wang L. J. Chem. Res. 2004; 186
• 68 Roszkowski P, Maurin JK, Czarnocki Z. Tetrahedron: Asymmetry 2006; 17: 1415
• 69 Seubert J, Thomas H, Andrews P. DE 2362539, 1975 ; Chem. Abstr. 1975, 84, 5007.