18404-43-8Relevant articles and documents
Production of the Cytotoxic Cardenolide Glucoevatromonoside by Semisynthesis and Biotransformation of Evatromonoside by a Digitalis lanata Cell Culture
Munkert, Jennifer,Santiago Franco, Marina,Nolte, Elke,Thaís Silva, Izabella,Oliveira Castilho, Rachel,Melo Ottoni, Flaviano,Schneider, Naira F. Z.,Oliveira, M?nica C.,Taubert, Helge,Bauer, Walter,Andrade, Saulo F.,Alves, Ricardo J.,Sim?es, Cláudia M. O.,Braga, Fern?o C.,Kreis, Wolfgang,De Pádua, Rodrigo Maia
, p. 1035 - 1043 (2017/09/05)
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.
Stereochemical survey of digitoxin monosaccharides
Wang, Hua-Yu Leo,Xin, Wenjun,Zhou, Maoquan,Stueckle, Todd A.,Rojanasakul, Yon,O'Doherty, George A.
, p. 73 - 78 (2011/04/17)
A stereochemically diverse array of monosaccharide analogues of the trisaccharide-based cardiac glycoside natural product digitoxin has been synthesized using a de novo asymmetric approach. The analogues were tested for cytotoxicity against the NCI panel of 60 human cancer cell lines and in more detail against nonsmall cell human lung cancer cells (NCI-H460). The results were compared with digitoxin and its aglycone digitoxigenin. Three novel digitoxin monosaccharide analogues with β-d-digitoxose, α-l-rhamnose, and α-l-amicetose sugar moieties showed excellent selectivity and activity. Further investigation revealed that digitoxin α-l-rhamnose and α-l-amicetose analogues displayed similar antiproliferation effects but with at least 5-fold greater potency in apoptosis induction than digitoxin against NCI-H460. This study demonstrates the ability to improve the digitoxin anticancer activity by modification of the stereochemistry and substitution of the carbohydrate moiety of this known cardiac drug.
De novo approach to 2-deoxy-β-glycosides: Asymmetric syntheses of digoxose and digitoxin
Zhou, Maoquan,O'Doherty, George A.
, p. 2485 - 2493 (2008/02/02)
A highly enantioselective and straightforward route to trisaccharide natural products digoxose and digitoxin has been developed. Key to this approach is the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The first total synthesis of natural product digoxose was accomplished in 19 total steps from achiral 2-acylfuran, and digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8β. This flexible synthetic strategy also allows for the preparation of mono- and disaccharide analogues of digoxose and digitoxin.
