Synthesis of Oligobenzamide α-Helix Mimetics

Abstract

The development of inhibitors of protein–protein interactions (PPIs) represents a major challenge in chemical biology. α-Helix-mediated PPIs represent a subclass that might be amenable to inhibition using scaffolds that reproduce the spatial projection of recognition groups produced by the helix; these ligands are termed proteomimetics. Such a generic scaffold approach requires robust chemistry that can be used to synthesize reasonably large libraries of compounds. Foldamers are defined as oligomers that adopt well-defined folded structures. An ultimate goal of research in this area is to be able to reproduce and surpass the functionality of natural biopolymers; again a key enabling technology in this pursuit is robust synthetic methodology with a broad substrate scope. When we started our research program in this area seven years ago, we were drawn to aromatic oligoamide foldamers as potential proteomimetic scaffolds; however, in contrast to more widely studied β-peptide- and peptoid-based foldamers, the synthesis of aromatic oligoamides was less well developed in terms of monomer diversity and amenability to library synthesis. This account describes our efforts and, more generally, the development of methodologies for the synthesis of aromatic oligoamides during this period.

1 Introduction

1.1 Helix Mimetics-Based on Aromatic Oligoamides

1.2 Issues with Amide Bond Formation

2 N-Alkylated Oligobenzamides

3 O-Alkylated Oligobenzamides

4 Concluding Remarks

Key words

amides - oligomerization - peptidomimetics - solid-phase synthesis

• References

• 1 Gellman SH. Acc. Chem. Res. 1998; 31: 173
• 2 Hill DJ, Mio MJ, Prince RB, Hughes TS, Moore JS. Chem. Rev. 2001; 101: 3893
• 3 Foldamers: Structure, Properties, and Applications. Hecht S, Huc I. Wiley-VCH; Weinheim: 2007
• 4 Goodman CM, Choi S, Shandler S, DeGrado WF. Nat. Chem. Biol. 2007; 3: 252
• 5 Guichard G, Huc I. Chem. Commun. 2011; 47: 5933
• 6 Seebach D, Gardiner J. Acc. Chem. Res. 2008; 41: 1366
• 7 Cheng RP, Gellman SH, DeGrado WF. Chem. Rev. 2001; 101: 3219
• 8 Horne WS, Gellman SH. Acc. Chem. Res. 2008; 41: 1399
• 9 Vasudev PG, Chatterjee S, Shamala N, Balaram P. Chem. Rev. 2011; 111: 657
• 10 Berlicki Ł, Pilsl L, Wéber E, Mándity IM, Cabrele C, Martinek TA, Fülöp F, Reiser O. Angew. Chem. Int. Ed. 2012; 51: 2208
• 11 Fischer L, Guichard G. Org. Biomol. Chem. 2010; 8: 3101
• 12 Fowler SA, Blackwell HE. Org. Biomol. Chem. 2009; 7: 1508
• 13 Park M, Wetzler M, Jardetzky TS, Barron AE. PLoS ONE 2013; 8: e58874
• 14 Lee J, Udugamasooriya DG, Lim H.-S, Kodadek T. Nat. Chem. Biol. 2010; 6: 258
• 15 Levine PM, Imberg K, Garabedian MJ, Kirshenbaum K. J. Am. Chem. Soc. 2012; 134: 6912
• 16 Hjelmgaard T, Nielsen J. Eur. J. Org. Chem. 2013; 3574
• 17 Hjelmgaard T, Faure S, Staerk D, Taillefumier C, Nielsen J. Eur. J. Org. Chem. 2011; 4121
• 18 Chen F, Zhu N.-Y, Yang D. J. Am. Chem. Soc. 2004; 126: 15980
• 19 Brown RA, Diemer V, Webb SJ, Clayden J. Nat. Chem. 2013; 5: 853
• 20 Dutot L, Wright K, Gaucher A, Wakselman M, Mazaleyrat J.-P, Zotti MD, Peggion C, Formaggio F, Toniolo C. J. Am. Chem. Soc. 2008; 130: 5986
• 21 Zhang D.-W, Zhao X, Hou J.-L, Li Z.-T. Chem. Rev. 2012; 112: 5271
• 22 Saraogi I, Hamilton AD. Chem. Soc. Rev. 2009; 38: 1726
• 23 Gong B. Acc. Chem. Res. 2008; 41: 1376
• 24 Ramesh VV. E, Priya G, Kotmale AS, Gonnade RG, Rajamohanan PR, Sanjayan GJ. Chem. Commun. 2012; 48: 11205
• 25 Roy A, Prabhakaran P, Baruah PK, Sanjayan GJ. Chem. Commun. 2011; 47: 11593
• 26 Prabhakaran P, Kale SS, Puranik VG, Rajamohanan PR, Chetina O, Howard JA. K, Hofmann H.-J, Sanjayan GJ. J. Am. Chem. Soc. 2008; 130: 17743
• 27 Sánchez-García D, Kauffmann B, Kawanami T, Ihara H, Takafuji M, Delville M.-H, Huc I. J. Am. Chem. Soc. 2009; 131: 8642
• 28 Yan Y, Qin B, Shu Y, Chen X, Yip YK, Zhang D, Su H, Zeng H. Org. Lett. 2009; 11: 1201
• 29 Ferrand Y, Kendhale AM, Garric J, Kauffmann B, Huc I. Angew. Chem. Int. Ed. 2010; 49: 1778
• 30 Delsuc N, Godde F, Kauffmann B, Léger J.-M, Huc I. J. Am. Chem. Soc. 2007; 129: 11348
• 31 Garric J, Leger J.-M, Huc I. Angew. Chem. Int. Ed. 2005; 44: 1945
• 32 Delsuc N, Léger J.-M, Massip S, Huc I. Angew. Chem. Int. Ed. 2007; 46: 214
• 33 Campbell F, Plante J, Carruthers C, Hardie MJ, Prior TJ, Wilson AJ. Chem. Commun. 2007; 224
• 34 Ferguson JS, Yamato K, Liu R, He L, Zeng XC, Gong B. Angew. Chem. Int. Ed. 2009; 48: 3150
• 35 Zhu Y.-Y, Li C, Li G.-Y, Jiang X.-K, Li Z.-T. J. Org. Chem. 2008; 73: 1745
• 36 Hou J.-L, Shao X.-B, Chen G.-J, Zhou Y.-X, Jiang X.-K, Li Z.-T. J. Am. Chem. Soc. 2004; 126: 12386
• 37 Sanford AR, Yuan L, Feng W, Yamato K, Flowers RA, Gong B. Chem. Commun. 2005; 4720
• 38 Kang S.-W, Gothard CM, Maitra S, Wahab A.-T, Nowick JS. J. Am. Chem. Soc. 2007; 129: 1486
• 39 Ren C, Maurizot V, Zhao H, Shen J, Zhou F, Ong WQ, Du Z, Zhang K, Su H, Zeng H. J. Am. Chem. Soc. 2011; 133: 13930
• 40 Qin B, Ren C, Ye R, Sun C, Chiad K, Chen X, Li Z, Xue F, Su H, Chass GA, Zeng H. J. Am. Chem. Soc. 2010; 132: 9564
• 41 Azzarito V, Long K, Murphy NS, Wilson AJ. Nat. Chem. 2013; 5: 161
• 42 Wilson AJ. Chem. Soc. Rev. 2009; 38: 3289
• 43 Thompson AD, Dugan A, Gestwicki JE, Mapp AK. ACS Chem. Biol. 2012; 7: 1311
• 44 Surade S, Blundell TL. Chem. Biol. 2012; 19: 42
• 45 Baptiste B, Godde F, Huc I. ChemBioChem 2009; 10: 1765
• 46 Cheng P.-N, Liu C, Zhao M, Eisenberg D, Nowick JS. Nat. Chem. 2012; 4: 927
• 47 Shin Y.-H, Mortenson DE, Satyshur KA, Forest KT, Gellman SH. J. Am. Chem. Soc. 2013; 135: 8149
• 48 Fülöp L, Mándity IM, Juhász G, Szegedi V, Hetényi A, Wéber E, Bozsó Z, Simon D, Benkő M, Király Z, Martinek TA. PLoS ONE 2012; 7; e39485
• 49 Azzarito V, Prabhakaran P, Bartlett AI, Murphy NS, Hardie MJ, Kilner CA, Edwards TA, Warriner SL, Wilson AJ. Org. Biomol. Chem. 2012; 10: 6469
• 50 Campbell F, Plante JP, Edwards TA, Warriner SL, Wilson AJ. Org. Biomol. Chem. 2010; 8: 2344
• 51 Plante JP, Burnley T, Malkova B, Webb ME, Warriner SL, Edwards TA, Wilson AJ. Chem. Commun. 2009; 34: 5091
• 52 Kushal S, Lao BB, Henchey LK, Dubey R, Mesallati H, Traaseth NJ, Olenyuk BZ, Arora PS. Proc. Natl. Acad. Sci. U. S. A. 2013; 110: 15602
• 53 LaBelle JL, Katz SG, Bird GH, Gavathiotis E, Stewart ML, Lawrence C, Fisher JK, Godes M, Pitter K, Kung AL, Walensky LD. J. Clin. Invest. 2012; 122: 2018
• 54 Orner BP, Ernst JT, Hamilton AD. J. Am. Chem. Soc. 2001; 123: 5382
• 55 Ko E, Liu J, Burgess K. Chem. Soc. Rev. 2011; 40: 4411
• 56 Kazi A, Sun J, Doi K, Sung S.-S, Takahashi Y, Yin H, Rodriguez JM, Becerril J, Berndt N, Hamilton AD, Wang H.-G, Sebti SM. J. Biol. Chem. 2011; 286: 9382
• 57 Saraogi I, Hamilton AD. Biochem. Soc. Trans. 2008; 36: 1414
• 58 Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. CNS Drug Rev. 2006; 12: 250
• 59 Roth B. Prog. Med. Chem. 2002; 40: 1
• 60 Kondo K, Ogawa H, Yamashita H, Miyamoto H, Tanaka M, Nakaya K, Kitano K, Yamamura Y, Nakamura S, Onogawa T, Mori T, Tominaga M. Bioorg. Med. Chem. 1999; 7: 1743
• 61 Mera H, Takata T In Ullmann’s Encyclopedia of Industrial Chemistry . Vol. 17. Wiley-VCH; Weinheim: 2012: 573
• 62 Le Guen A, Klapper M, Müllen K. Macromolecules 1998; 31: 6559
• 63 Schleuss T, Abbel R, Gross M, Schollmeyer D, Frey H, Maskos M, Berger R, Kilbinger A. Angew. Chem. Int. Ed. 2006; 45: 2969
• 64 Davis JM, Tsou LK, Hamilton AD. Chem. Soc. Rev. 2007; 36: 326
• 65 Ahn J.-M, Han S.-Y. Tetrahedron Lett. 2007; 48: 3543
• 66 Plante J, Campbell F, Malkova B, Kilner C, Warriner SL, Wilson AJ. Org. Biomol. Chem. 2008; 6: 138
• 67 Saraogi I, Incarvito C, Hamilton A. Angew. Chem. Int. Ed. 2008; 47: 9691
• 68 Shaginian A, Whitby L, Hong S, Hwang I, Farooqi B, Searcey M, Chen J, Vogt P, Boger D. J. Am. Chem. Soc. 2009; 131: 5564
• 69 Ravindranathan P, Lee T.-K, Yang L, Centenera MM, Butler L, Tilley WD, Hsieh J.-T, Ahn J.-M, Raj GV. Nat. Commun. 2013; 4: 1923
• 70 Yap JL, Cao X, Vanommeslaeghe K, Jung K.-Y, Peddaboina C, Wilder PT, Nan A, MacKerell AD, Smythe WR, Fletcher S. Org. Biomol. Chem. 2012; 10: 2928
• 71 Saraogi I, Hebda JA, Becerril J, Estroff LA, Miranker AD, Hamilton AD. Angew. Chem. Int. Ed. 2010; 49: 736
• 72 Whitby LR, Boger DL. Acc. Chem. Res. 2012; 45: 1698
• 73 Prabhakaran P, Azzarito V, Jacobs T, Hardie MJ, Kilner CA, Edwards TA, Warriner SL, Wilson AJ. Tetrahedron 2012; 68: 4485
• 74 Yin H, Frederick KK, Liu D, Wand AJ, DeGrado WF. Org. Lett. 2005; 8: 223
• 75 Choi S, Isaacs A, Clements D, Liu D, Kim H, Scott RW, Winkler JD, DeGrado WF. Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 6968
• 76 Lu F, Chi S.-W, Kim D.-H, Han K.-H, Kuntz ID, Guy RK. J. Comb. Chem. 2006; 8: 315
• 77 Shahian T, Lee GM, Lazic A, Arnold LA, Velusamy P, Roels CM, Guy RK, Craik CS. Nat. Chem. Biol. 2009; 5: 640
• 78 Thompson S, Vallinayagam R, Adler MJ, Scott RT. W, Hamilton AD. Tetrahedron 2012; 68: 4501
• 79 Marimganti S, Cheemala MN, Ahn J.-M. Org. Lett. 2009; 11: 4418
• 80 Prabhakaran P, Barnard A, Murphy NS, Kilner CA, Edwards TA, Wilson AJ. Eur. J. Org. Chem. 2013; 3504
• 81 Kulikov OV, Thompson S, Xu H, Incarvito CD, Scott RT. W, Saraogi I, Nevola L, Hamilton AD. Eur. J. Org. Chem. 2013; 3433
• 82 Roughley S, Jordan A. J. Med. Chem. 2011; 54: 3451
• 83 Pattabiraman V, Bode J. Nature 2011; 480: 471
• 84 Montalbetti CA. G. N, Falque V. Tetrahedron 2005; 61: 10827
• 85 Valeur E, Bradley M. Chem. Soc. Rev. 2009; 38: 606
• 86 Murphy NS, Prabhakaran P, Azzarito V, Plante JP, Hardie MJ, Kilner CA, Warriner SL, Wilson AJ. Chem. Eur. J. 2013; 19: 5546
• 87 Kulikov OV, Hamilton DH. RSC Adv. 2012; 2: 2454
• 88 Qi T, Deschrijver T, Huc I. Nat. Protoc. 2013; 8: 693
• 89 Yamaguchi K, Matsumura G, Kagechika H, Azumaya I, Ito Y, Itai A, Shudo K. J. Am. Chem. Soc. 1991; 113: 5474
• 90 Itai A, Toriumi Y, Tomioka N, Kagechika H, Azumaya I, Shudo K. Tetrahedron Lett. 1989; 30: 6177
• 91 Saito S, Toriumi Y, Tomioka N, Itai A. J. Org. Chem. 1995; 60: 4715
• 92 Tanatani A, Yokoyama A, Azumaya I, Takahura Y, Mitsui C, Shiro M, Uchiyama M, Muranaka A, Kobayashi N, Yokozawa T. J. Am. Chem. Soc. 2005; 127: 8553
• 93 Azumaya I, Okamoto T, Imabeppu F, Takayanai H. Tetrahedron 2003; 59: 2325
• 94 Fujimoto N, Matsumura M, Azumaya I, Nishiyama S, Masu H, Kagechika H, Tanatani A. Chem. Commun. 2013; 48: 4809
• 95 Bong DT, Clark TD, Granja JR, Ghadiri MR. Angew. Chem. Int. Ed. 2001; 40: 988
• 96 Campbell F, Wilson AJ. Tetrahedron Lett. 2009; 50: 2236
• 97 Woodward RB, Au-Yeung BW, Balaram P, Browne LJ, Ward DE, Au-Yeung BW, Card PJ, Chen CH. J. Am. Chem. Soc. 1981; 103: 3213
• 98 Long K, Edwards T, Wilson A. Bioorg. Med. Chem. 2013; 21: 4034
• 99 Campbell F, Kilner CA, Wilson AJ. Tetrahedron Lett. 2010; 51: 1361
• 100 Wurtz NR, Turner JM, Baird EE, Dervan PB. Org. Lett. 2001; 3: 1201
• 101 Baptiste B, Douat-Casassus C, Laxmi-Reddy K, Godde F, Huc I. J. Org. Chem. 2010; 75: 7175
• 102 König H, Abbel R, Schollmeyer D, Kilbinger A. Org. Lett. 2006; 8: 1819
• 103 König H, Gorelik T, Kolb U, Kilbinger A. J. Am. Chem. Soc. 2007; 129: 704
• 104 Konig B, Papke U, Rodel M. New J. Chem. 2000; 24: 39
• 105 Klos J, Wurm F, König HM, Kilbinger AF. M. Macromolecules 2007; 40: 7827
• 106 Devos A, Remion J, Frisque-Hesbain AM, Colens A, Ghosez L. J. Chem. Soc., Chem. Commun. 1979; 24: 1180
• 107 Hjelmgaard T, Faure S, Staerk D, Taillefumier C, Nielsen J. Org. Biomol. Chem. 2011; 9: 6832
• 108 Hjelmgaard T, Faure S, De Santis E, Staerk D, Alexander BD, Edwards AA, Taillefumier C, Nielsen J. Tetrahedron 2012; 68: 4444
• 109 Hamuro Y, Geib SJ, Hamilton AD. J. Am. Chem. Soc. 1996; 118: 7529
• 110 Lee T.-K, Ahn J.-M. ACS Comb. Sci. 2010; 13: 107
• 111 Yi H.-P, Shao X.-B, Hou J.-L, Li C, Jiang X.-K, Li Z.-T. New J. Chem. 2005; 29: 1213