TY - JOUR AU - Munkert, Jennifer; Santiago Franco, Marina; Nolte, Elke; Thaís Silva, Izabella; Oliveira Castilho, Rachel; Melo Ottoni, Flaviano; Schneider, Naira F. Z.; Oliveira, Mônica C.; Taubert, Helge; Bauer, Walter; Andrade, Saulo F.; Alves, Ricardo J.; Simões, Cláudia M. O.; Braga, Fernão C.; Kreis, Wolfgang; de Pádua, Rodrigo Maia TI - Production of the Cytotoxic Cardenolide Glucoevatromonoside by Semisynthesis and Biotransformation of Evatromonoside by a Digitalis lanata Cell Culture SN - 0032-0943 SN - 1439-0221 PY - 2017 JO - Planta Med JF - Planta Medica LA - EN VL - 83 IS - 12/13 SP - 1035 EP - 1043 ET - 2017/05/09 DA - 2017/08/08 KW - Cardiac glycosides KW - Digitalis mariana KW - Digitalis lanata KW - Plantaginaceae KW - regioselective glycosylation KW - plant cell suspension culture AB - 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. PB - Georg Thieme Verlag KG DO - 10.1055/s-0043-109557 UR - http://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0043-109557 ER -