Recent Advances in the Synthesis of 5-(Hetero)aryl Uracil Derivatives

Dedicated to Professor Yong-Jun Chen on the occasion of his 60^th birthday.

Abstract

C5-Aryl/heteroaryl uracil-based compounds have attracted continuous interest because of their wide biological potential. In this review, we outline the primary synthetic methods used to prepare designated uracils, various combinations of which have been used to synthesize target compounds with potential biological activities. The significance of each approach and its limitations are also summarized.

1 Introduction

2 Coupling of Prefunctionalized Uracils with (Hetero)aryl Reagents

2.1 Negishi Coupling

2.2 Suzuki–Miyaura Coupling

2.3 Stille Coupling

3 Coupling of Functionalized Uracils with Nonactivated Aromatic (Hetero)cycles

3.1 Photochemically Induced Coupling

3.2 Palladium-Catalyzed Coupling

4 Coupling of Nonactivated Uracil/Uridine with Functionalized Aromatic (Hetero)cycles

4.1 Electrochemical Reduction

4.2 Transition-Metal-Catalyzed Coupling

4.3 Light-Promoted Coupling of Uracils with Diazonium Salts

5 Direct Coupling of Nonactivated Uracils with Nonactivated Aromatic (Hetero)cycles

6 Summary and Prospects

Key words

uracils - cross-coupling reaction - prefunctionalization - direct coupling - nucleosides - medicinal chemistry

Publication History

Received: 24 April 2023

Accepted after revision: 10 May 2023

Accepted Manuscript online:
10 May 2023

Article published online:
14 July 2023

• References

• 1 Lagoja IM. Chem. Biodiversity 2005; 2: 1
• 2 Ascoli A. Hoppe-Seyler’s Z. Physiol. Chem. 1901; 31: 161
• 3 Brown DJ. The Pyrimidines: The Chemistry of Heterocyclic Compounds, Vol. 52. Wiley; New York: 1994
• 4 Heidelberger C, Chaudhuri NK, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer RJ, Pleven E, Scheiner J. Nature 1957; 179: 663
• 5 Novikov MS, Geisman AN. Chem. Heterocycl. Compd. (N. Y.) 2014; 49: 1426
• 6 Pałasz A, Cież D. Eur. J. Med. Chem. 2015; 97: 582
• 7 Grabovskiy SA, Murinov YI, Kabal’nova NN. Curr. Org. Chem. 2012; 16: 2389
• 8 Xin-Ying Z, Yang-Yang W, Dong F, Xue-Sen FA. N. Youji Huaxue 2010; 30: 797
• 9 Baker BR, Kawazu M. J. Med. Chem. 1967; 10: 311
• 10 Bedi RK, Huang D, Wiedmer L, Li Y, Dolbois A, Wojdyla JA, Sharpe ME, Caflisch A, Sledz P. ACS Chem. Biol. 2020; 15: 618
• 11 Lamb YN. Drugs 2018; 78: 1501
• 12 Wen Z, Suzol SH, Peng J, Liang Y, Snoeck R, Andrei G, Liekens S, Wnuk SF. Arch. Pharm. (Weinheim, Ger.) 2017; 350: 1700023
• 13 Peyron C, Benhida R, Bories C, Loiseau PM. Bioorg. Chem. 2005; 33: 439
• 14 Pesnot T, Tedaldi LM, Jambrina PG, Rosta E, Wagner GK. Org. Biomol. Chem. 2013; 11: 6357
• 15 Bardagí JI, Rossi RA. Org. Prep. Proced. Int. 2009; 41: 479
• 16 Wagner GK, Pesnot T, Palcic MM, Jørgensen R. J. Biol. Chem. 2015; 290: 31162
• 17 Meltzer D, Ethan O, Arguin G, Nadel Y, Danino O, Lecka J, Sévigny J, Gendron F.-P, Fischer B. Bioorg. Med. Chem. 2015; 23: 5764
• 18 Dalager M, Andersen NK, Kumar P, Nielsen P, Sharma PK. Org. Biomol. Chem. 2015; 13: 7040
• 19 Kovaliov M, Wachtel C, Yavin E, Fischer B. Org. Biomol. Chem. 2014; 12: 7844
• 20 Fritz Y, Wagenknecht H.-A. Front. Chem. 2019; 7: 659
• 21 Pawar MG, Nuthanakanti A, Srivatsan SG. Bioconjugate Chem. 2013; 24: 1367
• 22 Tanpure AA, Srivatsan SG. Chem. Eur. J. 2011; 17: 12820
• 23 Greco NJ, Tor Y. Tetrahedron 2007; 63: 3515
• 24 Greco NJ, Tor Y. J. Am. Chem. Soc. 2005; 127: 10784
• 25 Sidduri A, Tilley JW, Lou J, Tare N, Cavallo G, Frank K, Pamidimukkala A, Choi DS, Gerber L, Railkar A, Renzetti L. Bioorg. Med. Chem. Lett. 2013; 23: 1026
• 26 Das K, Pink M, Rajca S, Rajca A. J. Am. Chem. Soc. 2006; 128: 5334
• 27 Majid TN, Knochel P. Tetrahedron Lett. 1990; 31: 4413
• 28 Duddu R, Eckhardt M, Furlong M, Knoess HP, Berger S, Knochel P. Tetrahedron 1994; 50: 2415
• 29 Stevenson TM, Prasad AS. B, Citineni JR, Knochel P. Tetrahedron Lett. 1996; 37: 8375
• 30 Bhanu Prasad AS, Stevenson TM, Citineni JR, Nyzam V, Knochel P. Tetrahedron 1997; 53: 7237
• 31 Gong L.-Z, Knochel P. Synlett 2005; 267
• 32 Balkenhohl M, Ziegler DS, Desaintjean A, Bole LJ, Kennedy AR, Hevia E, Knochel P. Angew. Chem. Int. Ed. 2019; 58: 12898
• 33 Miyaura N, Yamada K, Suzuki A. Tetrahedron Lett. 1979; 20: 3437
• 34 Miyaura N, Suzuki A. J. Chem. Soc., Chem. Commun. 1979; 866
• 35 Gallagher-Duval S, Hervé G, Sartori G, Enderlin G, Len C. New J. Chem. 2013; 37: 1989
• 36 Rahman M, Ghosh S, Bhattacherjee D, Zyryanov GV, Bagdi Kumar A, Hajra A. Asian J. Org. Chem. 2022; 11: e202200179
• 37 Lussier T, Hervé G, Enderlin G, Len C. RSC Adv. 2014; 4: 46218
• 38 Serrano JL. Chem. Rec. 2022; 22: e202200179
• 39 Shih Y.-C, Chien T.-C. Tetrahedron 2011; 67: 3915
• 40 Čapek P, Cahová H, Pohl R, Hocek M, Gloeckner C, Marx A. Chem. Eur. J. 2007; 13: 6196
• 41 Cahová H, Havran L, Brázdilová P, Pivoñková H, Pohl R, Fojta M, Hocek M. Angew. Chem., Int. Ed. Engl. 2008; 47: 2059
• 42 Raindlová V, Pohl R, Šanda M, Hocek M. Angew. Chem. Int. Ed. 2010; 49: 1064
• 43 Sartori G, Enderlin G, Hervé G, Len C. Synthesis 2012; 44: 767
• 44 Sartori G, Hervé G, Enderlin G, Len C. Synthesis 2013; 45: 330
• 45 Ejlersen M, Lou C, Sanghvi YS, Tor Y, Wengel J. Chem. Commun. 2018; 54: 8003
• 46 Fresneau N, Hiebel M.-A, Agrofoglio LA, Berteina-Raboin S. Molecules 2012; 17: 14409
• 47 Kapdi A, Gayakhe V, Sanghvi YS, García J, Lozano P, da Silva I, Pérez J, Serrano JL. RSC Adv. 2014; 4: 17567
• 48 Gayakhe V, Ardhapure A, Kapdi AR, Sanghvi YS, Serrano JL, García L, Pérez J, García J, Sánchez G, Fischer C, Schulzke C. J. Org. Chem. 2016; 81: 2713
• 49 Bhilare S, Gayakhe V, Ardhapure AV, Sanghvi YS, Schulzke C, Borozdina Y, Kapdi AR. RSC Adv. 2016; 6: 83820
• 50 Serrano JL, Gaware S, Pérez JA, Pérez J, Lozano P, Kori S, Dandela R, Sanghvi YS, Kapdi AR. Dalton Trans. 2022; 51: 2370
• 51 Shaughnessy KH. Chem. Rec. 2022; 22: e202200190
• 52 Handa S, Andersson MP, Gallou F, Reilly J, Lipshutz BH. Angew. Chem. Int. Ed. 2016; 55: 4914
• 53 Serrano JL, García L, Pérez J, Lozano P, Correia J, Kori S, Kapdi AR, Sanghvi YS. Organometallics 2020; 39: 4479
• 54 Soli ED, Surber BW, Reed AD. J. Labelled Compd. Radiopharm. 2021; 64: 254
• 55 Hirano K, Miura M, Miura W. Synthesis 2017; 49: 4745
• 56 Snieckus V, Quesnelle C. Synthesis 2018; 50: 4413
• 57 Dow NW, Pedersen PS, Chen TQ, Blakemore DC, Dechert-Schmitt A.-M, Knauber T, MacMillan DW. C. J. Am. Chem. Soc. 2022; 144: 6163
• 58 Wicke L, Engels JW. Bioconjugate Chem. 2012; 23: 627
• 59 Zhang X.-H, Xu Y.-Z. Magn. Reson. Chem. 2016; 54: 887
• 60 Krause A, Hertl A, Muttach F, Jäschke A. Chem. Eur. J. 2014; 20: 16613
• 61 Seki K.-i, Matsuda K, Ohkura K. Chem. Lett. 1987; 16: 175
• 62 Ohkura K, Sugaoi T, Nishijima K.-I, Kuge Y, Seki K.-i. Tetrahedron Lett. 2002; 43: 3113
• 63 Yang Q, Wei T, He Y, Liang Y, Zhang Z.-T. Helv. Chim. Acta 2015; 98: 953
• 64 Saporito D, Rodriguez SA, Baumgartner MT. Aust. Chem. J. 2019; 72: 978
• 65 Rossi RA, Pierini AB, Peñéñory AB. Chem. Rev. 2003; 103: 71
• 66 Franchi L, Rinaldi M, Vignaroli G, Innitzer A, Radi M, Botta M. Synthesis 2010; 3927
• 67 Liang Y, Gloudeman J, Wnuk SF. J. Org. Chem. 2014; 79: 4094
• 68 Merritt EA, Olofsson B. Angew. Chem. Int. Ed. 2009; 48: 9052
• 69 Arun V, Reddy PO. V, Pilania M, Kumar D. Eur. J. Org. Chem. 2016; 2096
• 70 Médebielle M, Oturan MA, Pinson J, Savéant J.-M. Tetrahedron Lett. 1993; 34: 3409
• 71 Balasubramaniyam T, Oh K.-I, Jin H.-S, Ahn H.-B, Kim B.-S, Lee J.-H. Int. J. Mol. Sci. 2021; 22: 9552
• 72 Čerñová M, Pohl R, Hocek M. Eur. J. Org. Chem. 2009; 3698
• 73 Čerñová M, Čerña I, Pohl R, Hocek M. J. Org. Chem. 2011; 76: 5309
• 74 Shang Y, Wu C, Gao Q, Liu C, Li L, Zhang X, Cheng H.-G, Liu S, Zhou Q. Nat. Commun. 2021; 12: 2988
• 75 Ball LT, Lloyd-Jones GC, Russell CA. Science 2012; 337: 1644
• 76 Cresswell AJ, Lloyd-Jones GC. Chem. Eur. J. 2016; 22: 12641
• 77 Liu A.-D, Wang Z.-L, Liu L, Cheng L. J. Org. Chem. 2021; 86: 16434
• 78 Liu A.-D, Wang Z.-L, Liu L, Cheng L. Curr. Protoc. 2022; 2: e432
• 79 Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
• 80 Kim KH, Lee HS, Kim JN. Tetrahedron Lett. 2011; 52: 6228
• 81 Chen F, Feng Z, He C.-Y, Wang H.-Y, Guo Y.-L, Zhang X. Org. Lett. 2012; 14: 1176
• 82 Kianmehr E, Torabi M, Khalkhali Rezazadeh M, Faghih N, Khan KM. Eur. J. Org. Chem. 2015; 2796
• 83 Davarani SS. H, Fumani NS, Arvin-Nezhad H, Moradi F. Tetrahedron Lett. 2008; 49: 710
• 84 Das VK, Bharali P, Konwar BK, Mikkola J.-P, Shchukarev A, Thakur AJ. New J. Chem. 2016; 40: 1935