Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction

Nikolay S. Sitnikov, Antonina S. Kokisheva, Georgy K. Fukin, Jörg Martin Neudörfl, Hannah Sutorius, Aram Prokop, Valery V. Fokin, Hans Günther Schmalz, Alexey Yu Fedorov

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The synthesis of several new heterocyclic structural analogs of the natural antimitotic agent allocolchicine is reported. As a key step an intramolecular Pd-catalyzed C-H arylation reaction was used to close the seven-membered ring fused with two electron-rich aryl fragments. The stereostructure of the target compounds was determined by X-ray crystal analysis. The primary biological assessment of the synthesized compounds was carried out on human lymphoma cells. Several allocolchicinoids were determined to possess antiproliferative and apoptosis-inducing activity in the micromolar concentration range. The synthesis of indole-derived structural analogs of natural antimitotic agent allocolchicine is reported. In a key step, an intramolecular Pd-catalyzed C-H arylation reaction serves to construct the polycyclic ring system, by connecting the two electron-rich arene fragments.

Original languageEnglish
Pages (from-to)6481-6492
Number of pages12
JournalEuropean Journal of Organic Chemistry
Volume2014
Issue number29
DOIs
Publication statusPublished - 1 Oct 2014
Externally publishedYes

Fingerprint

Antimitotic Agents
congeners
indoles
fragments
analogs
Electrons
rings
apoptosis
synthesis
electrons
Apoptosis
X rays
Crystals
cells
crystals
x rays
allocolchicine
indole

Keywords

  • Antitumor agents
  • C-H activation
  • Colchicinoids
  • Conformation analysis
  • Heterogeneous catalysis
  • Medicinal chemistry
  • Nitrogen heterocycles

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Sitnikov, N. S., Kokisheva, A. S., Fukin, G. K., Neudörfl, J. M., Sutorius, H., Prokop, A., ... Fedorov, A. Y. (2014). Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction. European Journal of Organic Chemistry, 2014(29), 6481-6492. https://doi.org/10.1002/ejoc.201402850

Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction. / Sitnikov, Nikolay S.; Kokisheva, Antonina S.; Fukin, Georgy K.; Neudörfl, Jörg Martin; Sutorius, Hannah; Prokop, Aram; Fokin, Valery V.; Schmalz, Hans Günther; Fedorov, Alexey Yu.

In: European Journal of Organic Chemistry, Vol. 2014, No. 29, 01.10.2014, p. 6481-6492.

Research output: Contribution to journalArticle

Sitnikov, NS, Kokisheva, AS, Fukin, GK, Neudörfl, JM, Sutorius, H, Prokop, A, Fokin, VV, Schmalz, HG & Fedorov, AY 2014, 'Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction', European Journal of Organic Chemistry, vol. 2014, no. 29, pp. 6481-6492. https://doi.org/10.1002/ejoc.201402850
Sitnikov, Nikolay S. ; Kokisheva, Antonina S. ; Fukin, Georgy K. ; Neudörfl, Jörg Martin ; Sutorius, Hannah ; Prokop, Aram ; Fokin, Valery V. ; Schmalz, Hans Günther ; Fedorov, Alexey Yu. / Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction. In: European Journal of Organic Chemistry. 2014 ; Vol. 2014, No. 29. pp. 6481-6492.
@article{efac042687bf4d469149c68769222575,
title = "Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction",
abstract = "The synthesis of several new heterocyclic structural analogs of the natural antimitotic agent allocolchicine is reported. As a key step an intramolecular Pd-catalyzed C-H arylation reaction was used to close the seven-membered ring fused with two electron-rich aryl fragments. The stereostructure of the target compounds was determined by X-ray crystal analysis. The primary biological assessment of the synthesized compounds was carried out on human lymphoma cells. Several allocolchicinoids were determined to possess antiproliferative and apoptosis-inducing activity in the micromolar concentration range. The synthesis of indole-derived structural analogs of natural antimitotic agent allocolchicine is reported. In a key step, an intramolecular Pd-catalyzed C-H arylation reaction serves to construct the polycyclic ring system, by connecting the two electron-rich arene fragments.",
keywords = "Antitumor agents, C-H activation, Colchicinoids, Conformation analysis, Heterogeneous catalysis, Medicinal chemistry, Nitrogen heterocycles",
author = "Sitnikov, {Nikolay S.} and Kokisheva, {Antonina S.} and Fukin, {Georgy K.} and Neud{\"o}rfl, {J{\"o}rg Martin} and Hannah Sutorius and Aram Prokop and Fokin, {Valery V.} and Schmalz, {Hans G{\"u}nther} and Fedorov, {Alexey Yu}",
year = "2014",
month = "10",
day = "1",
doi = "10.1002/ejoc.201402850",
language = "English",
volume = "2014",
pages = "6481--6492",
journal = "Annalen der Pharmacie",
issn = "0075-4617",
publisher = "Wiley-VCH Verlag",
number = "29",

}

TY - JOUR

T1 - Synthesis of indole-derived allocolchicine congeners through Pd-catalyzed intramolecular C-H arylation reaction

AU - Sitnikov, Nikolay S.

AU - Kokisheva, Antonina S.

AU - Fukin, Georgy K.

AU - Neudörfl, Jörg Martin

AU - Sutorius, Hannah

AU - Prokop, Aram

AU - Fokin, Valery V.

AU - Schmalz, Hans Günther

AU - Fedorov, Alexey Yu

PY - 2014/10/1

Y1 - 2014/10/1

N2 - The synthesis of several new heterocyclic structural analogs of the natural antimitotic agent allocolchicine is reported. As a key step an intramolecular Pd-catalyzed C-H arylation reaction was used to close the seven-membered ring fused with two electron-rich aryl fragments. The stereostructure of the target compounds was determined by X-ray crystal analysis. The primary biological assessment of the synthesized compounds was carried out on human lymphoma cells. Several allocolchicinoids were determined to possess antiproliferative and apoptosis-inducing activity in the micromolar concentration range. The synthesis of indole-derived structural analogs of natural antimitotic agent allocolchicine is reported. In a key step, an intramolecular Pd-catalyzed C-H arylation reaction serves to construct the polycyclic ring system, by connecting the two electron-rich arene fragments.

AB - The synthesis of several new heterocyclic structural analogs of the natural antimitotic agent allocolchicine is reported. As a key step an intramolecular Pd-catalyzed C-H arylation reaction was used to close the seven-membered ring fused with two electron-rich aryl fragments. The stereostructure of the target compounds was determined by X-ray crystal analysis. The primary biological assessment of the synthesized compounds was carried out on human lymphoma cells. Several allocolchicinoids were determined to possess antiproliferative and apoptosis-inducing activity in the micromolar concentration range. The synthesis of indole-derived structural analogs of natural antimitotic agent allocolchicine is reported. In a key step, an intramolecular Pd-catalyzed C-H arylation reaction serves to construct the polycyclic ring system, by connecting the two electron-rich arene fragments.

KW - Antitumor agents

KW - C-H activation

KW - Colchicinoids

KW - Conformation analysis

KW - Heterogeneous catalysis

KW - Medicinal chemistry

KW - Nitrogen heterocycles

UR - http://www.scopus.com/inward/record.url?scp=84941135440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941135440&partnerID=8YFLogxK

U2 - 10.1002/ejoc.201402850

DO - 10.1002/ejoc.201402850

M3 - Article

VL - 2014

SP - 6481

EP - 6492

JO - Annalen der Pharmacie

JF - Annalen der Pharmacie

SN - 0075-4617

IS - 29

ER -