Syntheses of Biologically Active 2-Arylcyclopropylamines

Abstract

The 2-arylcyclopropylamine (ACPA) motif is often seen in biologically active compounds. This review focuses on the synthesis of biologically active ACPAs and categorizes, by reaction type, the synthetic methods used toward such compounds.

1 Introduction

2 Cyclopropanation Using Diazo Compounds

2.1 Styrene

2.2 Cinnamate

2.3 Vinyl Phthalimide

2.4 Vinyl Acetamide

2.5 Oxazolone

2.6 Diketopiperazine

3 Cyclopropanation Using Ylides

3.1 Cinnamate

3.2 Nitrostyrene

3.3 Oxirane

3.4 Nitroacetate

4 Transformation of Cyclopropanes

4.1 Iodocyclopropane

4.2 Aminocyclopropane

5 Miscellaneous Methods

5.1 Kulinkovich Reaction

5.2 Three-Component Reaction

5.3 Intramolecular Nucleophilic Cyclization

5.4 Intramolecular Mitsunobu Reaction

5.5 Rearrangement from Cyclobutanone

6 Summary

Key words

arylcyclopropylamine - cyclopropanes - biologically active compounds

• References

• 1a Tsai T.-Y, Hsu T, Chen C.-T, Cheng J.-H, Yeh T.-K, Chen X, Huang C.-Y, Chang C.-N, Yeh K.-C, Hsieh S.-H, Chien C.-H, Chang Y.-W, Huang C.-H, Huang Y.-W, Huang C.-L, Wu S.-H, Wang M.-H, Lu C.-T, Chao Y.-S, Jiaang W.-T. Bioorg. Med. Chem. 2009; 17: 2388
• 1b Lindberg J, Sigurdsson S, Löwgren S, Andersson HO, Sahlberg C, Noréen R, Fridborg K, Zhang H, Unge T. Eur. J. Biochem. 2002; 269: 1670
• 1c Suzuki T, Miyata N. J. Med. Chem. 2011; 54: 8236
• 1d Ogasawara D, Itoh Y, Tsumoto H, Kakizawa T, Mino K, Fukuhara K, Nakagawa H, Hasegawa M, Sasaki R, Mizukami T, Miyata N, Suzuki T. Angew. Chem. Int. Ed. 2013; 52: 8620
• 1e Singer R, Mawson P, Derby N, Rodriguez A, Kizima L, Menon R, Goldman D, Kenney J, Aravantinou M, Seidor S, Gettie A, Blanchard J, Piatak M, Lifson JD, Fernández-Romero JA, Robbiani M, Zydowsky TM. Sci. Transl. Med. 2012; 4: 150ra123
• 1f Khan MN. A, Suzuki T, Miyata N. Med. Res. Rev. 2013; 33: 873
• 2a Vangveravong S, Nichols DE. J. Org. Chem. 1995; 60: 3409
• 2b Kazuta Y, Hirano K, Natsume K, Yamada S, Kimura R, Matsumoto S.-i, Furuichi K, Matsuda A, Shuto S. J. Med. Chem. 2003; 46: 1980
• 2c Kazuta Y, Matsuda A, Shuto S. J. Org. Chem. 2002; 67: 1669
• 3 Yang M, Culhane JC, Szewczuk LM, Jalili P, Ball HL, Machius M, Cole PA, Yu H. Biochemistry 2007; 46: 8058
• 4 Rousseaux S, Liégault B, Fagnou K. Chem. Sci. 2012; 3: 244

For representative reviews see
• 5a Lebel H, Marcoux J.-F, Molinaro C, Charette AB. Chem. Rev. 2003; 103: 977
• 5b Pietruszka J. Chem. Rev. 2003; 103: 1051
• 5c Wessjohann LA, Brandt W, Thiemann T. Chem. Rev. 2003; 103: 1625
• 6 As for the stereochemistry described in the following schemes, the wedged lines indicate the relative configuration of stereogenic centers (cis or trans), whereas the R or S descriptor indicates the absolute configuration. Unless otherwise noted, all compounds are racemic mixtures.
• 7 Pryde DC, Cook AS, Burring DJ, Jones LH, Foll S, Platts MY, Sanderson V, Corless M, Stobie A, Middleton DS. Bioorg. Med. Chem. 2007; 15: 142
• 8 Pannala M, Kher S, Wilson N, Gaudette J, Sircar I, Zhang S.-H, Bakhirev A, Yang G, Yuen P, Gorcsan F, Sakurai N, Barbosa M, Cheng J.-F. Bioorg. Med. Chem. Lett. 2007; 17: 5978
• 9 Andreotti D, Arista L, Cardullo F, Spada S, Thewlis KM, Ward SE. PCT Int. Appl. WO 2006087169A1 I, 2006
• 10a Minucci S, Mai A, Mattevi A. PCT Int. Appl. WO 2011131576, 2011
• 10b Binda C, Valente S, Romanenghi M, Pilotto S, Cirilli R, Karytinos A, Ciossani G, Botrugno OA, Forneris F, Tardugno M, Edmondson DE, Minucci S, Mattevi A, Mai A. J. Am. Chem. Soc. 2010; 132: 6827
• 11 Benelkebir H, Hodgkinson C, Duriez PJ, Hayden AL, Bulleid RA, Crabb SJ, Packham G, Ganesan A. Bioorg. Med. Chem. 2011; 19: 3709
• 12 Evans DA, Woerpel KA, Hinman MM, Faul MM. J. Am. Chem. Soc. 1991; 113: 726
• 13 Li H, Xue F, Kraus JM, Ji H, Labby KJ, Mataka J, Delker SL, Martásek P, Roman LJ, Poulos TL, Silverman RB. Bioorg. Med. Chem. 2013; 21: 1333
• 14a Högberg M, Sahlberg C, Engelhardt P, Noréen R, Kangasmetsä J, Johansson NG, Öberg B, Vrang L, Zhang H, Sahlberg B.-L, Unge T, Lövgren S, Fridborg K, Bäckbro K. J. Med. Chem. 1999; 42: 4150
• 14b Sahlberg C, Noréen R, Högberg M, Engelhardt P. PCT Int. Appl. WO 9936406, 1999
• 14c Sahlberg C, Noréen R, Engelhardt P, Högberg M, Kangasmetsä J, Vrang L, Zhang H. Bioorg. Med. Chem. Lett. 1998; 8: 1511
• 15 Tu W, Fan J, Zhang H, Xu G, Liu Z, Qu J, Yang F, Zhang L, Luan T, Yuan J, Gong A, Feng J, Sun P, Dong Q. Bioorg. Med. Chem. Lett. 2014; 24: 141
• 16a Décor A, Greul J, Heilmann EK, Schwarz H.-G, Gesing E.-R, Frackenpohl J, Elbe H.-L, Wiese WB, Portz D, Ilg K, Malsam O, Lösel P, Lümmen P, Görgens U, Coqueron P.-Y, Martelletti A, Desbordes P, Gary S, Christian I, Welz C. PCT Int. Appl. WO 2014177487, 2014
• 16b Altmann E, Hommel U, Lorthiois EL. J, Maibaum JK, Ostermann N, Quancard J, Randl SA, Vulpetti A, Rogel O. PCT Int. Appl. WO 2014002051, 2014
• 16c Ortega Muños A, Fyfe MC. T, Martinell Pedemonte M, Estiarte Martínez Md. l. Á, Valls Vidal N, Kurz G, Castro Palomino Laria JC. PCT Int. Appl. WO 2013057320, 2013
• 16d Hruschka S, Rosen TC, Yoshida S, Kirk KL, Fröhlich R, Wibbeling B, Haufe G. Bioorg. Med. Chem. 2008; 16: 7148
• 16e Gooden DM, Schmidt DM. Z, Pollock JA, Kabadi AM, McCafferty DG. Bioorg. Med. Chem. Lett. 2008; 18: 3047
• 16f Rosen TC, Yoshida S, Fröhlich R, Kirk KL, Haufe G. J. Med. Chem. 2004; 47: 5860
• 16g Yoshida S, Meyer OG. J, Rosen TC, Haufe G, Ye S, Sloan MJ, Kirk KL. J. Med. Chem. 2004; 47: 1796
• 17 Reichelt A, Gaul C, Frey RR, Kennedy A, Martin SF. J. Org. Chem. 2002; 67: 4062
• 18 Corey EJ, Myers AG. Tetrahedron Lett. 1984; 25: 3559
• 19a Pietruszka J, Solduga G. Synlett 2008; 1349
• 19b Luithle JE. A, Pietruszka J. Liebigs Ann./Recl. 1997; 2297
• 19c Pietruszka J, Widenmeyer M. Synlett 1997; 977
• 19d Pietruszka JR, Solduga G. Eur. J. Org. Chem. 2009; 5998
• 19e Luithle JE. A, Pietruszka J. J. Org. Chem. 1999; 64: 8287
• 20 Zirkle CL, Kaiser C, Tedeschi DH, Tedeschi RE, Burger A. J. Med. Pharm. Chem. 1962; 5: 1265
• 21a Wurz RP, Charette AB. J. Org. Chem. 2004; 69: 1262
• 21b Charette AB, Wurz RP, Ollevier T. Helv. Chim. Acta 2002; 85: 4468
• 22 Morellato L, Lefas-Le Gall M, Langlois M, Caignard D.-H, Renard P, Delagrange P, Mathé-Allainmat M. Bioorg. Med. Chem. Lett. 2013; 23: 430
• 23 Tchilibon S, Kim S.-K, Gao Z.-G, Harris BA, Blaustein JB, Gross AS, Duong HT, Melman N, Jacobson KA. Bioorg. Med. Chem. 2004; 12: 2021
• 24 Vangveravong S, Kanthasamy A, Lucaites VL, Nelson DL, Nichols DE. J. Med. Chem. 1998; 41: 4995
• 25a Vallgårda J, Appelberg U, Csöregh I, Hacksell U. J. Chem. Soc., Perkin Trans. 1 1994; 461
• 25b Vallgårda J, Appelberg U, Arvidsson LE, Hjorth S, Svensson BE, Hacksell U. J. Med. Chem. 1996; 39: 1485
• 26 Chen J, Levant B, Jiang C, Keck TM, Newman AH, Wang S. J. Med. Chem. 2014; 57: 4962
• 27 Aggarwal VK, de Vicente J, Bonnert RV. Org. Lett. 2001; 3: 2785
• 28 Zhang J.-L, Hong Chan PW, Che C.-M. Tetrahedron Lett. 2003; 44: 8733
• 29 Hughes RA, Tølløfsrud M, Bryant N, Kaboli M, Hennum M, Bonge-Hansen T. Tetrahedron Lett. 2013; 54: 318
• 30 Davies H.-ML, Panaro SA. Tetrahedron 2000; 56: 4871
• 31 Guay D, Beaulieu C, Truchon J.-F, Jagadeeswar Reddy T, Zamboni R, Bayly CI, Methot N, Rubin J, Ethier D, Percival MD. Bioorg. Med. Chem. Lett. 2009; 19: 5392
• 32 Campbell MM, Horwell DC, Mahon MF, Pritchard MC, Walford SP. Bioorg. Med. Chem. Lett. 1993; 3: 667
• 33 Neelamegam R, Ricq EL, Malvaez M, Patnaik D, Norton S, Carlin SM, Hill IT, Wood MA, Haggarty SJ, Hooker JM. ACS Chem. Neurosci. 2012; 3: 120
• 34 Ueda R, Suzuki T, Mino K, Tsumoto H, Nakagawa H, Hasegawa M, Sasaki R, Mizukami T, Miyata N. J. Am. Chem. Soc. 2009; 131: 17536
• 35a He X, Zhong M, Zhang T, Yang J, Wu Z, Xiao Y, Guo H, Qiu G, Hu X. Eur. J. Med. Chem. 2012; 48: 338
• 35b He X, Zhong M, Yang J, Wu Z, Xiao Y, Guo H, Hu X. Chem. Biol. Drug. Des. 2012; 79: 771
• 35c He X, Qiu G, Yang J, Xiao Y, Wu Z, Qiu G, Hu X. Eur. J. Med. Chem. 2010; 45: 3818
• 36a Shiozaki M, Maeda K, Miura T, Ogoshi Y, Haas J, Fryer AM, Laird ER, Littmann NM, Andrews SW, Josey JA, Mimura T, Shinozaki Y, Yoshiuchi H, Inaba T. Bioorg. Med. Chem. Lett. 2009; 19: 1575
• 36b Georgakopoulou G, Kalogiros C, Hadjiarapoglou LC. Synlett 2001; 1843
• 36c Fryer AM, Shiozaki M, Littmann NM, Inaba T, Andrews SW, Yasue K, Laird ER, Yokota M, Haas J, Imai H, Maeda K, Shinozaki Y, Hori Y. PCT Int. Appl. WO 2005058808, 2005
• 37 Ogasawara D, Suzuki T, Mino K, Ueda R, Khan NM. A, Matsubara T, Koseki K, Hasegawa M, Sasaki R, Nakagawa H, Mizukami T, Miyata N. Bioorg. Med. Chem. 2011; 19: 3702
• 38a Zhang H. PCT Int. Appl. WO 2014194280, 2014
• 38b Ortega Muños A, Castro-Palomino Laria J, Fyfe MC. T. PCT Int. Appl. WO 2011131697, 2011
• 38c Guibourt N, Ortega Muños A, Castro-Palomino Laria J. PCT Int. Appl. WO 2010084160, 2010
• 38d Guibourt N, Ortega Muños A, Castro-Palomino Laria J. PCT Int. Appl. WO 2010043721, 2010
• 39a Zhang H, Liu J, Zhang L, Yao H, Sun H. Bioorg. Med. Chem. Lett. 2012; 22: 3598
• 39b Vianello P, Botrugno OA, Cappa A, Dal Zuffo R, Dessanti P, Mai A, Marrocco B, Mattevi A, Meroni G, Minucci S, Stazi G, Thaler F, Trifiró P, Valente S, Villa M, Varasi M, Mercurio C. J. Med. Chem. 2016; 59: 1501
• 40 Dejonghe J.-P, Peeters K, Renard M. PCT Int. Appl. WO 2008018822, 2008
• 41a Moreau B, Alberico D, Lindsay VN. G, Charette AB. Tetrahedron 2012; 68: 3487
• 41b Moreau B, Charette AB. J. Am. Chem. Soc. 2005; 127: 18014
• 42a Dey K, Gao DA, Goldberg DR, Heim-Ri-Ether A, Mangette JE, Mugge IA, Snow R, Swinamer AD, Wu J.-P, Xiong Z, Yang Y. PCT Int. Appl. WO 2009052078, 2009
• 42b Wurz RP, Charette AB. Org. Lett. 2003; 5: 2327
• 43 Cai S, Dinitroff M, McKennon T, Reider M, Robarge L, Ryckman D, Shang X, Therrien J. Org. Process Res. Dev. 2004; 8: 353
• 44 Miyamura S, Araki M, Ota Y, Itoh Y, Yasuda S, Masada M, Taniguchi T, Sowa Y, Sakai T, Suzuki T, Itami K, Yamaguchi J. Org. Biomol. Chem. 2016; 14: 8576
• 45 Miyamura S, Araki M, Suzuki T, Yamaguchi J, Itami K. Angew. Chem. Int. Ed. 2015; 54: 846
• 46a Faler CA, Joullié MM. Org. Lett. 2007; 9: 1987

For the Kulinkovich reaction, see:
• 46b Kulinkovich OG, Sviridov SV, Vasilevskii DA. Synthesis 1991; 234
• 46c Lee J, Cha JK. J. Org. Chem. 1997; 62: 1584
• 46d Chaplinski V, Winsel H, Kordes M, de Meijere A. Synlett 1997; 111
• 47 Ishikawa S, Sheppard TD, D’Oyley JM, Kamimura A, Motherwell WB. Angew. Chem. Int. Ed. 2013; 52: 10060
• 48a Shiozaki M, Maeda K, Miura T, Kotoku M, Yamasaki T, Matsuda I, Aoki K, Yasue K, Imai H, Ubukata M, Suma A, Yokota M, Hotta T, Tanaka M, Hase Y, Haas J, Fryer AM, Laird ER, Littmann NM, Andrews SW, Josey JA, Mimura T, Shinozaki Y, Yoshiuchi H, Inaba T. J. Med. Chem. 2011; 54: 2839
• 48b Shiozaki M, Imai H, Maeda K, Miura T, Yasue K, Suma A, Yokota M, Ogoshi Y, Haas J, Fryer AM, Laird ER, Littmann NM, Andrews SW, Josey JA, Mimura T, Shinozaki Y, Yoshiuchi H, Inaba T. Bioorg. Med. Chem. Lett. 2009; 19: 6213
• 49 Khile AS, Patel J, Trivedi N, Pradhan NS. PCT Int. Appl. WO 2011132083, 2011
• 50 Du Bois DJ, Hurst DN, Loughhead DG, Maag H, Manka J, Smith DB. PCT Int. Appl. WO 2009043784, 2009
• 51 Chen B.-C, Ngu K, Guo P, Lio W, Sundeen JE, Weinstein DS, Atwal KS, Ahmad S. Tetrahedron Lett. 2001; 42: 6227