Synthesis 2019; 51(07): 1611-1622
DOI: 10.1055/s-0037-1610673
paper
© Georg Thieme Verlag Stuttgart · New York

A Facile Synthetic Approach to Nonracemic Substituted Pyrrolo-allocolchicinoids Starting from Natural Colchicine

Ekaterina S. Shchegravina
a   Department of Organic Chemistry, Nizhny Novgorod State University, 23 Gagarin Avenue, 603950 Nizhny Novgorod, Russian Federation   Email: afnn@rambler.ru
,
Elena V. Svirshchevskaya
b   Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16/10 Miklukho-Maklaya Street, 117997 Moscow, Russian Federation
,
Hans-Günther Schmalz
c   Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Cologne, Germany
,
a   Department of Organic Chemistry, Nizhny Novgorod State University, 23 Gagarin Avenue, 603950 Nizhny Novgorod, Russian Federation   Email: afnn@rambler.ru
› Author Affiliations
T This work was supported by the Russian Science Foundation (Project 16-13-10248).
Further Information

Publication History

Received: 28 October 2018

Accepted after revision: 05 November 2018

Publication Date:
13 December 2018 (online)


Abstract

A six-step semisynthetic approach towards chiral nonracemic pyrrolo-allocolchicinoids starting from naturally occurring colchicine was developed. The synthetic scheme includes an electrocyclic tropolone ring contraction to afford allocolchicinic acid followed by the Curtius reaction, giving the corresponding aniline. The Sandmeyer reaction and copper-mediated hydrazination gave hydrazine-substituted allocolchicine. This was introduced into the Fischer indole synthesis, affording libraries of regioisomeric indole-based allocolchicine congeners.

Supporting Information

 
  • References

  • 1 Downing KH, Nogales E. Curr. Opin. Cell Biol. 1998; 10: 16
    • 2a Li W, Sun H, Xu S, Zhu Z, Xu J. Future Med. Chem. 2017; 9: 1765
    • 2b Patil R, Patil SA, Beaman KD, Patil SA. Future Med. Chem. 2016; 8: 1291
    • 2c Sears JE, Boger DL. Acc. Chem. Res. 2015; 48: 653
    • 2d Sitnikov NS, Fedorov AYu. Russ. Chem. Rev. 2013; 82: 393
    • 2e Dohle W, Jourdan FL, Menchon G, Prota AE, Foster PA, Mannion P, Hamel E, Thomas MP, Kasprzyk P, Ferrandis GE, Steinmetz MO, Leese MP, Potter BV. L. J. Med. Chem. 2018; 61: 1031
    • 2f Zhou P, Liu Y, Zhou L, Zhu K, Feng K, Zhang H, Liang Y, Jiang H, Luo C, Liu M, Wang Y. J. Med. Chem. 2016; 59: 10329
    • 2g Nicolaou KC, Yin J, Mandal D, Erande RD, Klahn P, Jin M, Aujay M, Sandoval J, Gavrilyuk J, Vourloumis D. J. Am. Chem. Soc. 2016; 138: 1698
    • 2h Yan J, Chen J, Zhang S, Hu J, Huang L, Li X. J. Med. Chem. 2016; 59: 5264
    • 2i Liu Y.-N, Wang J.-J, Ji Y.-T, Zhao G.-D, Tang L.-Q, Zhang C.-M, Guo X.-L, Liu Z.-P. J. Med. Chem. 2016; 59: 5341
    • 2j Marzo-Mas A, Barbier P, Breuzard G, Allegro D, Falomir E, Murga J, Carda M, Peyrot V, Marco JA. Eur. J. Med. Chem. 2017; 126: 526
    • 2k Song M.-Y, Cao C.-Y, He Q.-R, Dong Q.-M, Li D, Tang J.-J, Gao J.-M. Bioorg. Med. Chem. 2017; 25: 5290
  • 3 Capraro H.-G, Brossi A. In The Alkaloids: Chemistry and Pharmacology . Vol. 23. Brossi A. Academic Press; New York: 1984: 398 Vol. 23
    • 4a Sarı I, Birlik M, Kaşifoğlu T. Eur. J. Rheumatol. 2014; 1: 21
    • 4b Soskind R, Abazia DT, Bridgeman MB. Expert Opin. Pharmacother. 2017; 18: 1115
    • 4c Morales A, Pari M, López-Lisbona R, Cubero N, Dorca J, Rosell A. Respiration 2016; 91: 251
    • 5a Lennerz C, Barman M, Tantawy M, Sopher M, Whittaker P. Int. J. Cardiol. 2017; 249: 127
    • 5b Tong DC, Wilson AM, Layland J. Heart 2016; 102: 995
    • 5c Verma S, Eikelboom JW, Nidorf SM, Al-Omran M, Gupta NI, Teoh H, Friedrich JO. BMC Cardiovasc. Disord. 2015; 15: 96
    • 6a Holm JG, Ivyanskiy I, Thomsen SF. J. Dermatol. Treat. 2018; 29: 80
    • 6b Zhang J, Rane G, Dai X, Shanmugam MK, Arfuso F, Samy RP, Lai MK, Kappei D, Kumar AP, Sethi G. Ageing Res. Rev. 2016; 25: 55
    • 7a Dickinson M, Juneja S. Br. J. Haematol. 2009; 146: 465
    • 7b Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, Pollak U, Koren G, Bentur Y. Clin. Toxicol. 2010; 48: 407
    • 7c Malysheva YB, Combes S, Allegro D, Peyrot V, Knochel P, Gavryushin AE, Fedorov AYu. Bioorg. Med. Chem. 2012; 20: 4271
    • 7d Kuznetsova NR, Svirshchevskaya EV, Sitnikov NS, Abodo L, Sutorius H, Zapke J, Velder J, Thomopoulou P, Oschkinat H, Prokop A, Schmalz H.-G, Fedorov AYu, Vodovozova EL. Russ. J. Bioorg. Chem. 2013; 39: 543
    • 8a Sitnikov N, Velder J, Abodo L, Cuvelier N, Neudörfl J, Prokop A, Krause G, Fedorov AY, Schmalz H.-G. Chem. Eur. J. 2012; 18: 12096
    • 8b Sitnikov NS, Kokisheva AS, Fukin GK, Neudörfl J.-M, Sutorius H, Prokop A, Fokin VV, Schmalz H.-G, Fedorov AYu. Eur. J. Org. Chem. 2014; 6481
    • 8c Sitnikov NS, Sintsov AV, Allegro D, Barbier P, Combes S, Abodo OL, Prokop A, Schmalz H.-G, Fedorov AYu. MedChemComm 2015; 6: 2158
    • 8d Shchegravina ES, Knyazev DI, Beletskaya IP, Svirshchevskaya EV, Schmalz H.-G, Fedorov AYu. Eur. J. Org. Chem. 2016; 5620
    • 8e Shchegravina ES, Maleev AA, Ignatov SK, Gracheva IuA, Stein A, Schmalz H.-G, Gavryushin AE, Zubareva AA, Svirshchevskaya EV, Fedorov AYu. Eur. J. Med. Chem. 2017; 141: 51
    • 9a Voitovich YV, Shegravina ES, Sitnikov NS, Faerman V, Fokin VV, Schmalz H.-G, Combes S, Allegro D, Barbier P, Beletskaya IP, Svirshchevskaya EV, Fedorov AYu. J. Med. Chem. 2015; 58: 692
    • 9b Gracheva IuA, Voitovich IV, Faerman VI, Sitnikov NS, Myrsikova EV, Schmalz H.-G, Svirshevskaya EV, Fedorov AYu. Eur. J. Med. Chem. 2017; 126: 432
    • 9c Gracheva IA, Svirshchevskaya EV, Zaburdaeva EA, Fedorov AYu. Synthesis 2017; 49: 4335
    • 9d Gracheva IuA, Svirshchevskaya EV, Faerman VI, Beletskaya IP, Fedorov AYu. Synthesis 2018; 50: 2753
    • 10a Mauger C, Mignani G. Adv. Synth. Catal. 2005; 347: 773
    • 10b Surry DS, Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 6338
    • 10c Surry DS, Buchwald SL. Chem. Sci. 2011; 2: 27
    • 11a Wolter M, Klapars A, Buchwald SL. Org. Lett. 2001; 3: 3803
    • 11b Evano G, Blanchard N, Toumi M. Chem. Rev. 2008; 108: 3054
    • 11c Jiang L, Lu X, Zhang H, Jiang Y, Ma D. J. Org. Chem. 2009; 74: 4542
    • 11d Bhunia S, Pawar GG, Kumar SV, Jiang Y, Ma D. Angew. Chem. Int. Ed. 2017; 56: 16136
    • 12a Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
    • 12b Gribble GW. Indole Ring Synthesis: From Natural Products to Drug Discovery . John Wiley & Sons, Ltd; Chichester, UK: 2016
    • 12c Inman M, Moody CJ. Chem. Commun. 2011; 47: 788
    • 12d Taber DF, Tirunahari PK. Tetrahedron 2011; 67: 7195
    • 14a Windaus A. Justus Liebigs Ann. Chem. 1924; 439: 59
    • 14b Nicolaus N, Reball J, Sitnikov N, Velder J, Termath A, Fedorov AYu, Schmalz H.-G. Heterocycles 2011; 82: 1585
    • 15a Lim Y.-K, Cho C.-G. Tetrahedron Lett. 2004; 45: 1857
    • 15b Chae J, Buchwald SL. J. Org. Chem. 2004; 69: 3336
    • 15c Wagaw S, Yang BH, Buchwald SL. J. Am. Chem. Soc. 1999; 121: 10251
    • 15d Hughes DL. Org. Prep. Proced. Int. 1993; 25: 607
    • 15e Bright WL, Briscoe HT. J. Phys. Chem. 1933; 37: 787
  • 16 Martin RH. Angew. Chem., Int. Ed. Engl. 1974; 13: 649
  • 17 Cech J, Santavy F. Collect. Czech. Chem. Commun. 1949; 14: 532
  • 18 Yu J, Lian G, Zhang D. Synth. Commun. 2007; 37: 37
  • 19 Yusupov MK, Sadykov AS. Zh. Obshch. Khim. 1964; 34: 1677