Chemical Reactions of Indole Alkaloids That Enable Rapid Access to New Scaffolds for Discovery

Derek A. Leas; Daniel C. Schultz; Robert W. Huigens III

doi:10.1055/a-2048-8412

SynOpen, Table of Contents

CC BY 4.0 · SynOpen 2023; 07(02): 165-185
DOI: 10.1055/a-2048-8412

graphical review

Chemical Reactions of Indole Alkaloids That Enable Rapid Access to New Scaffolds for Discovery

Derek A. Leas

,

Daniel C. Schultz

,

Robert W. Huigens III ∗

Abstract

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Abstract

This graphical review provides a concise overview of indole alkaloids and chemical reactions that have been reported to transform both these natural products and derivatives to rapidly access new molecular scaffolds. Select biologically active compounds from these synthetic efforts are reported herein.

Keywords

indole alkaloids - yohimbine - vincamine - reserpine - chemical synthesis - ring distortion

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References

References

1a O’Connor S, Maresh JJ. Nat. Prod. Rep. 2006; 23: 532
1b Kochanowska-Karamyan AJ, Hamann MT. Chem. Rev. 2010; 110: 4489
1c Stöckigt J, Antonchick AP, Wu F, Waldmann H. Angew. Chem. Int. Ed. 2011; 50: 8538
1d Sears JE, Boger DL. Acc. Chem. Res. 2015; 48: 653
1e Carney DW, Lukesh JC, Brody DM, Brütsch MM, Boger DL. Proc. Natl. Acad. Sci. U. S. A. 2016; 113: 9691
1f Norwood VM, Huigens III RH. ChemBioChem 2019; 20: 2273

2a Dolby LJ, Sakai S.-I. J. Am. Chem. Soc. 1964; 86: 1890
2b Sakai S.-I, Kubo A, Katano K, Shinma N. Yakugaku Zasshi 1973; 93: 1165
2c Harley-Mason J. Atta-ur-Rahman Tetrahedron 1980; 36: 1057
2d Calverley MJ. J. Chem. Soc., Chem. Commun. 1981; 1209
2e Liu CT, Sun SC, Yu QS. J. Org. Chem. 1983; 48: 44
2f Schill G, Löwer H, Priester CU, Windhövel UF, Fritz H. Tetrahedron 1987; 43: 3729
2g Schill G, Priester CU, Windhövel UF, Fritz H. Tetrahedron 1987; 43: 3747
2h Magnus P, Mugrage B, DeLuca MR, Cain GA. J. Am. Chem. Soc. 1990; 112: 5220
2i Magnus P, Mugrage B, DeLuca M, Cain GA. J. Am. Chem. Soc. 1989; 111: 786
2j Schill G, Priester CU, Windhövel UF, Fritz H. Tetrahedron 1990; 46: 1211
2k Magnus P, Giles M, Bonnert R, Johnson G, McQuire L, DeLuca M, Merritt A, Kim CS, Vicker N. J. Am. Chem. Soc. 1993; 115: 8116
2l Foster GH, Harley-Mason J, Waterfield WR. Chem. Commun. 1967; 21
2m Sakai S.-I, Yamanaka E, Dolby LJ. Heterocycles 1976; 4: 981
2n Banks BJ, Calverley MJ, Edwards PD, Harley-Mason J. Tetrahedron Lett. 1981; 22: 1631
2o Calverley MJ, Harley-Mason J, Quarrie SA, Edwards PD. Tetrahedron 1981; 37: 1547
2p Calverley MJ. J. Chem. Res., Miniprint 1983; 8: 1848
2q Schill G, Priester CU, Windhövel UF, Fritz H. Helv. Chim. Acta 1986; 69: 438
2r Schill G, Priester CU, Windhövel UF, Fritz H. Tetrahedron 1987; 43: 3765
2s Takayama H, Masubuchi K, Kitajima M, Aimi N, Sakai S.-I. Tetrahedron 1989; 45: 1327
2t Takajama H, Kitajima M, Wongseripipatana S, Sakai S.-I. J. Chem. Soc., Perkin Trans. 1 1989; 1075
2u Takayama H, Odaka H, Aimi N, Sakai S.-I. Tetrahedron Lett. 1990; 31: 5483
2v Mahboobi S, Wagner W, Burgemeister T, Wiegrebe W. Arch. Pharm. 1994; 327: 463
2w Fernàndez J.-C, Valls N, Bosch J, Bonjoch J. J. Chem. Soc., Chem. Commun. 1995; 2317
2x Bonjoch J, Fernàndez J.-C, Valls N. J. Org. Chem. 1998; 63: 7338
2y Magnus P, Gazzard L, Hobson L, Payne AH, Lynch V. Tetrahedron Lett. 1999; 40: 5135
2z Magnus P, Gazzard L, Hobson L, Payne AH, Rainey TJ, Westlund N, Lynch V. Tetrahedron 2002; 58: 3423
2aa Kim Y, Heo J, Kim D, Chang S, Seo S. Nat. Commun. 2020; 11: 4761

3a Takayama H, Tominaga Y, Kitajima M, Aimi N, Sakai S.-I. J. Org. Chem. 1994; 59: 4381
3b Mahboobi S, Wagner W, Burgemeister T. Arch. Pharm. 1995; 328: 371
3c Sattely ES, Meek SJ, Malcolmson SJ, Schrock RR, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 943
3d Fokas D, Wang Z. Synth. Commun. 2008; 38: 3816
3e Fokas D, Kaselj M, Isome Y, Wang Z. ACS Comb. Sci. 2013; 15: 49
3f Fokas D, Hamzik JA. Synlett 2009; 581
3g Magnus P, Ladlow M, Elliott J, Kim CS. J. Chem. Soc., Chem. Commun. 1989; 518
3h Magnus P, Mendoza JS, Stamford A, Ladlow M, Willis P. J. Am. Chem. Soc. 1992; 114: 10232
3i Magnus P, Stamford A, Ladlow M. J. Am. Chem. Soc. 1990; 112: 8210
3j Magnus P, Mendoza J. Tetrahedron Lett. 1992; 33: 899
3k Yang J, Rallapalli SK, Cook JM. Tetrahedron Lett. 2010; 51: 815
3l Rannoux C, Roussi F, Martin M.-T, Guéritte F. Org. Biomol. Chem. 2011; 9: 4873
3m Kitajima M, Watanabe K, Maeda H, Kogure N, Takayama H. Org. Lett. 2016; 18: 1912
3n Yang Z, Tan Q, Jiang Y, Yang J, Su X, Qiao Z, Zhou W, He L, Qiu H, Zhang M. Angew. Chem. Int. Ed. 2021; 60: 13105
3o Li W, Wang Y, Qi H, Shi R, Li J, Chen S, Xu X.-M, Wang W.-L. Org. Biomol. Chem. 2021; 19: 8086

4a Albright JD, Goldmon L. J. Am. Chem. Soc. 1969; 91: 4317
4b Lampe-Tirions M, Kaisin M, Pecher J. Bull. Soc. Chim. Belg. 1971; 80: 27
4c Costa G, Riche C, Husson H.-P. Tetrahedron 1977; 33: 315
4d Kutney JP, Eigendorf GK, Matsue H, Murai A, Tanaka K, Sung WL, Wada K, Worth BR. J. Am. Chem. Soc. 1978; 100: 938
4e Sakai S.-I, Shinma N. Heterocycles 1976; 4: 985
4f Sakai S.-I, Yamamoto Y, Hasegawa S. Chem. Pharm. Bull. 1980; 28: 3454
4g Sakai S.-I, Yamamoto Y, Hasegawa S. Heterocycles 1980; 14: 85
4h Wan AS. C, Yokota M, Ogata K, Aimi N, Sakai S.-I. Heterocycles 1987; 26: 1211
4i Koike T, Takayama H, Sakai S.-I. Chem. Pharm. Bull. 1991; 39: 1677

5a Banerji A, Siddhanta AK. J. Indian Chem. Soc. 1982; 59: 542
5b Takayama H, Horigome M, Aimi N, Sakai S.-I. Tetrahedron Lett. 1990; 31: 1287
5c Paciaroni NG, Ratnayake R, Matthew JH, Norwood VM, Arnold AC, Dang LH, Luesch H, Huigens III RH. Chem. Eur. J. 2017; 23: 4327
5d Norwood VM, Brice-Tutt AC, Eans SO, Stacy HM, Shi G, Ratnayake R, Rocca JR, Abboud KA, Li C, Luesch H, McLaughlin JP, Huigens III RH. J. Med. Chem. 2020; 63: 5119
5e Srinivasulu V, Srikanth G, Khanfar MA, Abu-Yousef IA, Majdalawieh AF, Mazitschek R, Setty SC, Sebastian A, Al-Tel TH. J. Org. Chem. 2022; 87: 1377

6a Wenkert E, Garratt S, Dave KG. Can. J. Chem. 1964; 42: 489
6b Herbst D, Rees R, Hughes GA, Smith H. J. Med. Chem. 1966; 9: 864
6c Kutney JP, Abdurahman N, Le Quesne P, Piers E, Vlattas I. J. Am. Chem. Soc. 1966; 88: 3656
6d Kutney JP, Cretney WJ, Le Quesne P, McKague B, Piers E. J. Am. Chem. Soc. 1966; 88: 4756
6e Harley-Mason J, Atta-ur-Rahman, Beisler JA. Chem. Commun. 1966; 743
6f Dolby L, Gribble G. J. Org. Chem. 1967; 32: 1391
6g Takano S, Hirama M, Ogasawara K. J. Org. Chem. 1980; 45: 3729
6h Döé de Maindreville M, Lévy J. Bull. Soc. Chim. Fr. 1981; 2: 179
6i Wenkert E, Halls TD. J, Kwart LD, Magnusson G, Showalter HD. H. Tetrahedron 1981; 37: 4017
6j Takano S, Hirama M, Ogasawara K. Tetrahedron Lett. 1982; 23: 881
6k Kalaus G, Malkieh N, Katona I, Kajtar-Peredy M, Koritsanszky T, Kalman A, Szabo L, Szántay C. J. Org. Chem. 1985; 50: 3760
6l Abadi AH, Lankow S, Hoefgen B, Decker M, Kassack MU, Lehmann J. Arch. Pharm. 2002; 335: 367
6m Robaa D, Enzensperger C, AbdulAzm SE, Hefnawy MM, El-Subbagh HI, Wani TA, Lehmann J. J. Med. Chem. 2011; 54: 7422
6n Kutney JP, Abdurahman N, Gletsos C, Le Quesne P, Piers E, Vlattas I. J. Am. Chem. Soc. 1970; 92: 1727
6o Takano S, Chiba K, Yonaga M, Ogasawara K. J. Chem. Soc., Chem. Commun. 1980; 616
6p Atta-ur-Rahman; Beisler JA, Harley-Mason J. Tetrahedron 1980; 36: 1063
6q Takano S, Yonaga M, Chiba K, Ogasawara K. Tetrahedron Lett. 1980; 21: 3697
6r Takano S, Uchida W, Hatakeyama S, Ogasawara K. Chem. Lett. 1982; 11: 733
6s Node M, Nagasawa H, Fuji K. J. Am. Chem. Soc. 1987; 109: 7901
6t Node M, Nagasawa H, Fuji K. J. Org. Chem. 1990; 55: 517
6u Temme O, Taj S.-A, Andersson PG. J. Org. Chem. 1998; 63: 6007
6v Witt T, Hock FJ, Lehmann J. J. Med. Chem. 2000; 43: 2079
6w Rostom SA, Farghaly AM, Soliman FS, el-Semary MM, Elz S, Lehmann J. Arch. Pharm. 2001; 334: 241
6x Kanada RM, Ogasawara K. Tetrahedron Lett. 2001; 42: 7311
6y Kobayashi J, Sekiguchi M, Shimamoto S, Shigemori H, Ishiyama H, Ohsaki A. J. Org. Chem. 2002; 67: 6449
6z Hoefgen B, Decker M, Mohr P, Schramm AM, Rostom SA. F, El-Subbagh H, Schweikert PM, Rudolf DR, Kassack MU, Lehmann J. J. Med. Chem. 2006; 49: 760
6aa Enzensperger C, Kilian S, Ackermann M, Koch A, Kelch K, Lehmann J. Bioorg. Med. Chem. Lett. 2007; 17: 1399
6ab Robaa D, Kretschmer R, Siol O, Abulazm SE, Elkhawass E, Lehmann J, Enzensperger C. Arch. Pharm. 2010; 344: 28

7a Voskressensky LG, Borisova TN, Titov AA, Listratova AV, Kulikova LN, Varlamov AV, Khrustalev VN, Aleksandrov GG. Russ. Chem. Bull. 2012; 61: 1231
7b Voskressensky LG, Borisova TN, Kulikova LN, Varlamov AV, Catto M, Altomare C, Caroti A. Eur. J. Org. Chem. 2004; 2004: 3128
7c Voskressensky LG, Borisova TN, Kulikova LN, Doglova EG, Kleimenov AI, Sorokina EA, Titov AA, Varlamov AV. Chem. Heterocycl. Compd. 2007; 43: 587
7d Zhang L, Chang L, Hu H, Wang H, Yao Z.-J, Wang S. Chem. Eur. J. 2014; 20: 2925
7e Harley-Mason J. Atta-ur-Rahman Chem. Commun. 1967; 208
7f Takano S, Murakata C, Ogasawara K. Heterocycles 1980; 14: 1301
7g Lim H, Seong S, Kim Y, Seo S, Han S. J. Am. Chem. Soc. 2021; 143: 19966
7h Bailey PD, Hollinshead SP. Tetrahedron Lett. 1987; 28: 2879
7i Royer D, Yu YL, Hugel G, Lévy J. Tetrahedron 1998; 54: 6507

8a Movassaghi M, Schmidt MA, Ashenhurst JA. Org. Lett. 2008; 10: 4009
8b Trost BM, Brennan MK. Synthesis 2009; 3003
8c Kaur M, Singh M, Chadha N, Silakari O. Eur. J. Med. Chem. 2016; 123: 858
8d Mahadu YM, Shivani M, Murugesan S, Kondapalli VG, Sekhar C. Biomed. Pharmacother. 2021; 141: 111842
8e Boddy AJ, Bull JA. Org. Chem. Front. 2021; 8: 1026

9a Wenkert E, Bindra JS, Chang C.-J, Cochran DW, Schell FM. Acc. Chem. Res. 1974; 7: 46
9b Kuntiyong P, Inprung N, Phakdeeyothin K, Buaphan A, Thammapichai K. Tetrahedron 2020; 76: 131261
9c Bian Z.-G, Marvin CC, Martin SF. J. Am. Chem. Soc. 2013; 135: 10886
9d Chen P, Yang H, Zhang H, Chen W, Zhang Z, Zhang J, Li H, Wang X, Xie X, She X. Org. Lett. 2020; 22: 2022
9e Edmondson S, Danishefsky SJ, Sepp-Lorenzino L, Rosen N. J. Am. Chem. Soc. 1999; 121: 2147
9f Xu J, Liang L, Zheng H, Chi YR, Tong R. Nat. Commun. 2019; 10: 4754
9g Qian C, Li P, Sun J. Angew. Chem. Int. Ed. 2021; 60: 5871
9h Martin SF, Mortimore M. Tetrahedron Lett. 1990; 31: 4557
9i Mercado-Marin EV, Garcia-Reynaga P, Romminger S, Pimenta EF, Romney DK, Lodewyk MW, Williams DE, Andersen RJ, Miller SJ, Tantillo DJ, Berlinck RG. S, Sarpong R. Nature 2014; 509: 318
9j Finch N, Gemenden CW, Hsu IH.-C, Taylor WI. J. Am. Chem. Soc. 1963; 85: 1520

10a Zhao G, Xie X, Sun H, Yuan Z, Zhong Z, Tang S, She X. Org. Lett. 2016; 18: 2447
10b Stahl R, Borschberg H.-J. Helv. Chim. Acta 1994; 77: 1331
10c Finch N, Gemenden CW, Hsu IH.-C, Kerr A, Sim GA, Taylor WI. J. Am. Chem. Soc. 1965; 87: 2229
10d Phillipson JD, Hemingway SR. Phytochemistry 1975; 8: 1855
10e Váradi A, Marrone GF, Palmer TC, Narayan A, Szabó MR, Le Rouzic V, Grinnell SG, Subrath JJ, Warner E, Kalra S, Hunkele A, Pagirsky J, Eans SO, Medina JM, Xu J, Pan YX, Borics A, Pasternak GW, McLaughlin JP, Majumdar S. J. Med. Chem. 2016; 59: 8381
10f Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, Koyama F, Matsumoto K, Moriyama T, Yamamoto LT, Watanabe K, Murayama T, Horie S. J. Med. Chem. 2002; 45: 1949
10g Kamble SH, León F, King TI, Berthold EC, Lopera-Londoño C, Siva Rama Raju K, Hampson AJ, Sharma A, Avery BA, McMahon LR, McCurdy CR. ACS Pharmacol. Transl. Sci. 2020; 3: 1063
10h Keglevich A, Mayer S, Pápai R, Szigetvári Á, Sánta Z, Dékány M, Szántay CJr, Keglevich P, Hazai L. Molecules 2018; 23: 2574
10i Drathen TV, Hoffman F, Brasholz M. Chem. Eur. J. 2018; 24: 10253
10j Su Y, Huang G, Ye F, Qiao P, Ye J, Gao Y, Chen H. Org. Biomol. Chem. 2019; 17: 8811

11a Witkop B, James B, Patrick JB, Rosenblum MJ. J. Am. Chem. Soc. 1951; 73: 2641
11b Witkop B, Goodwin S. J. Am. Chem. Soc. 1953; 75: 3371
11c Janot M.-M, Goutarel R, Le Hir A, Tsatsasa G, Prelog V. Helv. Chim. Acta 1955; 38: 1073
11d Winterfeldt E. Liebigs Ann. Chem. 1971; 745: 23
11e Nakagawa M, Matsuki K, Hasegawa K, Hino T. J. Chem. Soc., Chem. Commun. 1982; 742
11f Carniaux JF, Kan-Fan C, Royer J, Husson HP. Tetrahedron Lett. 1997; 38: 2997
11g Jiang W, Alford VC, Qiu Y, Bhattacharjee S, John TW, Haynes-Johnson D, Kraft PJ, Lundeen SG, Sui Z. Bioorg. Med. Chem. 2004; 12: 1505
11h Pin F, Comesse S, Daïch A. Tetrahedron 2011; 27: 5564
11i Lancefield CS, Zhou L, Lébl T, Slawin AM. Z, Westwood NJ. Org. Lett. 2012; 14: 6166
11j Roxburgh CJ. Tetrahedron 1993; 49: 10749
11k Mental M, Breinbauer R. Curr. Org. Chem. 2007; 11: 159
11l Tratrat C, Giorgi-Renault S, Husson H.-P. Synlett 1998; 1071
11m Sigaut F, Didierdefresse B, Lévy J. Tetrahedron 2000; 56: 9641
11n Afsah EM, Fadda AA, Bondock S, Hammouda MM. Z. Naturforsch. 2009; 64b: 415
11o Mentel M, Peters M, Albering J, Breinbauer R. Tetrahedron 2011; 67: 965
11p Liu S, Scott JS, Kozmin SA. J. Org. Chem. 2013; 78: 8645
11q Yang Y, Bai Y, Sun S, Dai M. Org. Lett. 2014; 16: 6216
11r Wu K, Fang C, Kaur S, Liu P, Wang T. Synthesis 2018; 50: 2897
11s Leas DA, Dong Y, Garrison J, Wang X, Ezell E, Stack DE, Vennerstrom JL. J. Org. Chem. 2020; 85: 2846

12a Lachkar D, Denizot N, Bernadat G, Ahamada K, Beniddir MA, Dumontet V, Gallard J.-F, Guillot R, Leblanc K, N’nang EO, Turpin V, Kouklovsky C, Poupon E, Evanno L, Vincent G. Nat. Chem. 2017; 9: 793
12b Takayama H, Misawa K, Okada N, Ishikawa H, Kitajima M, Hatori Y, Murayama T, Wongseripipatana S, Tashima K, Matsumoto K, Horie S. Org Lett. 2006; 8: 5705
12c Ryckaert B, Hullaert J, Van Hecke K, Winne JM. Org. Lett. 2022; 24: 4119

13a Randriambola L, Quirion J.-C, Kan-Fan C, Husson H.-P. Tetrahedron 1987; 28: 2123
13b Kalaus G, Malkieh N, Kajtár-Peredy M, Brlik J, Szabó L, Szántay C. Heterocycles 1988; 27: 1179
13c Honty K, Szánty C, Kolonits P, Demeter A, Szántay C. Tetrahedron 1993; 49: 10421
13d Nemes A, Szántay CJr, Czibula L, Greiner I. Heterocycles 2007; 11: 2347
13e Woods JR, Riofski MV, Zheng MM, O’Banion MA, Mo H, Kirshner J, Colby DA. Bioorg. Med. Chem. Lett. 2013; 23: 5865
13f Ma Y.-H, Ge S.-W, Wang W, Sun BW. J. Mol. Struct. 2015; 1097: 87

14a Norwood VM, Murillo-Solano C, Goertzen MG, Brummel BR, Perry DL, Rocca JR, Chakrabarti D, Huigens III RH. ACS Omega 2021; 6: 20455
14b Paciaroni NG, Perry DL, Norwood VM, Solano CM, Huigens III RH. ACS Infect. Dis. 2020; 6: 159

15a Gaskell AJ, Joule JA. Tetrahedron 1968; 24: 5115
15b Sakai SI, Ogawa M. Chem. Pharm. Bull. 1978; 26: 678
15c Ross SP, Hoye TR. Nat. Chem. 2017; 9: 523
15d Mukaiyama T, Narasaka K, Hokonok H. J. Am. Chem. Soc. 1969; 91: 4317

16a Beatty JW, Stephenson CR. J. J. Am. Chem. Soc. 2014; 136: 10270
16b Gotoh H, Sears JE, Eschenmoser A, Boger DL. J. Am. Chem. Soc. 2012; 134: 13240
16c Seong S, Lim H, Han S. Chem 2019; 5: 353

17a Chen H, Ye F, Luo J, Gao Y. Org. Lett. 2019; 21: 7475
17b Guo W, Wang X, Zhang J, Zhang T, Lv H, Zhao C. Chem. Biol. Drug Des. 2022; 99: 535
17c Jiang J, Hu C. Molecules 2009; 14: 1852
17d Dong G, Wang S, Miao Z, Yao J, Zhang Y, Guo Z, Zhang W, Sheng C. J. Med. Chem. 2012; 55: 7593
17e Li ZG, Dong GQ, Wang SZ, Miao ZY, Yao JZ, Zhang WN, Sheng CQ. Chin. Chem. Lett. 2015; 26: 267
17f Koltai T. Open Access J. Oncol. Med. 2018; 1: 37
17g Hu X, Li D, Chu C, Li X, Wang X, Jia Y, Hua H, Xu F. Int. J. Mol. Sci. 2018; 19: 3403
17h Zhou P, Li XP, Jiang R, Chen Y, Lv XT, Guo XX, Tian K, Yuan DZ, Lv YW, Ran JH, Li J, Chen DL. Anticancer Drugs 2019; 30: 611
17i Jiang ZB, Huang JM, Xie YJ, Zhang YZ, Chang C, Lai HL, Wang W, Yao XJ, Fan XX, Wu QB, Xie C, Wang MF. J. Exp. Clin. Cancer Res. 2020; 39: 249
17j Chen S, Bi K, Wu S, Li Y, Huang Y, Sheng C, Dong G. Eur. J. Med. Chem. 2021; 220: 113544
17k Liang Y, Zhang H, Zhang X, Peng Y, Deng J, Wang Y, Li R, Liu L, Wang Z. Bioorg. Chem. 2022; 127: 105981