Planta Med 2017; 83(12/13): 1035-1043
DOI: 10.1055/s-0043-109557
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Production of the Cytotoxic Cardenolide Glucoevatromonoside by Semisynthesis and Biotransformation of Evatromonoside by a Digitalis lanata Cell Culture[*]

Jennifer Munkert**
Department of Biology, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany
,
Marina Santiago Franco**
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Elke Nolte
Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany
,
Izabella Thaís Silva
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Rachel Oliveira Castilho
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Flaviano Melo Ottoni
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Naira F. Z. Schneider
Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
,
Mônica C. Oliveira
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Helge Taubert
Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany
,
Walter Bauer
Department of Chemistry and Pharmacy, Friedrich-Alexander Universität, Erlangen-Nürnberg, Germany
,
Saulo F. Andrade
Department of Pharmaceutical Sciences, Universidade Federal de Rio Grande do Sul, Porto Alegre, Brazil
,
Ricardo J. Alves
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Cláudia M. O. Simões
Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil
,
Fernão C. Braga
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
,
Wolfgang Kreis
Department of Biology, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany
,
Rodrigo Maia de Pádua
Department of Pharmacy, Universidade Federal of Minas Gerais, Belo Horizonte, Brazil
› Author Affiliations
Further Information

Publication History

received 31 January 2017
revised 31 March 2017

accepted 12 April 2017

Publication Date:
09 May 2017 (eFirst)

Abstract

Recent studies demonstrate that cardiac glycosides, known to inhibit Na+/K+-ATPase in humans, have increased susceptibility to cancer cells that can be used in tumor therapy. One of the most promising candidates identified so far is glucoevatromonoside, which can be isolated from the endangered species Digitalis mariana ssp. heywoodii. Due to its complex structure, glucoevatromonoside cannot be obtained economically by total chemical synthesis. Here we describe two methods for glucoevatromonoside production, both using evatromonoside obtained by chemical degradation of digitoxin as the precursor. 1) Catalyst-controlled, regioselective glycosylation of evatromonoside to glucoevatromonoside using 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide as the sugar donor and 2-aminoethyldiphenylborinate as the catalyst resulted in an overall 30 % yield. 2) Biotransformation of evatromonoside using Digitalis lanata plant cell suspension cultures was less efficient and resulted only in overall 18 % pure product. Structural proof of products has been provided by extensive NMR data. Glucoevatromonoside and its non-natural 1–3 linked isomer neo-glucoevatromonoside obtained by semisynthesis were evaluated against renal cell carcinoma and prostate cancer cell lines.

* Dedicated to Professor Dr. Max Wichtl in recognition of his outstanding contribution to pharmacognosy research.


** These authors contributed equally to this manuscript.


Supporting Information