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Usage

Uses

Used in Pharmaceutical Industry:
(5beta)-3beta-[(2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide is used as a pharmaceutical agent for its cytotoxic, anti-migratory, anti-invasive, and anti-proliferative effects in all tumor cells. Its ability to target and inhibit the growth and spread of cancer cells makes it a promising candidate for the development of novel anticancer drugs.
Used in Cancer Research:
In the field of cancer research, (5beta)-3beta-[(2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide serves as a valuable tool for understanding the molecular mechanisms underlying tumor growth and metastasis. Its potent anti-cancer properties can be further investigated to identify potential therapeutic targets and develop more effective treatment strategies for various types of cancer.
Used in Drug Delivery Systems:
Similar to gallotannin, (5beta)-3beta-[(2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide can also benefit from the development of novel drug delivery systems. These systems can help improve the compound's bioavailability, delivery, and therapeutic outcomes, making it more effective in combating cancer cells. Various organic and metallic nanoparticles can be employed as carriers for the targeted delivery of (5beta)-3beta-[(2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide to cancer cells, enhancing its overall efficacy.

InChI:InChI=1/C29H44O7/c1-16-26(32)23(30)14-25(35-16)36-19-6-9-27(2)18(13-19)4-5-22-21(27)7-10-28(3)20(8-11-29(22,28)33)17-12-24(31)34-15-17/h12,16,18-23,25-26,30,32-33H,4-11,13-15H2,1-3H3/t16?,18-,19-,20-,21?,22?,23?,25+,26-,27+,28-,29+/m1/s1

Upstream product

• 71-63-6 digitoxin 
• 108942-62-7 1,3,4-Tri-O-acetyl-2-deoxy-α/β-D-ribohexopyranose 
• 143-62-4 (+)-digitoxigenin 
• 16479-50-8 digitoxigen O-[2',6'-dideoxy-β-D-ribo-hexopyranosyl]-(1->4)-(2,6-dideoxy-β-D-ribo-hexopyranoside) 
• 88109-04-0 (21',23'-epoxy-14'-hydroxy-24'-nor-5'β,14'β-chola-20',22'-dien-3'β-yl) 2,6-dideoxy-4-O-(p-methoxybenzoyl)-3-O-(N-methylcarbamoyl)-D-ribo-hexopyranoside 
• 88109-01-7 2,6-dideoxy-4-O-(p-methoxybenzoyl)-3-O-(N-methylcarbamoyl)-D-ribo-hexose 
• 912454-91-2 (2R,6R)-2-(digitoxigenoxy)-3,6-dihydro-6-methyl-2H-pyran 
• 30657-17-1 (21',23'-epoxy-14'-hydroxy-24'-nor-5'β,14'β-chola-20',22'-dien-3'β-yl) 2,6-dideoxy-β-D-ribo-hexopyranoside 
• 17063-59-1 Acetic acid (2R,3R,4S)-3-acetoxy-6-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(5-oxo-2,5-dihydro-furan-3-yl)-hexadecahydro-cyclopenta[a]phenanthren-3-yloxy]-2-methyl-tetrahydro-pyran-4-yl ester 

Relevant academic research and scientific papers

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

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.

Assembly of digitoxin by gold(I)-catalyzed glycosidation of glycosyl o-alkynylbenzoates

Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d- digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages.

Stereochemical survey of digitoxin monosaccharides

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.

A direct comparison of the anticancer activities of digitoxin MeON-Neoglycosides and O-Glycosides

Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology; however, an investigation of anticancer activity as a function of oligosaccharide chain length has not yet been performed. We generated mono-, di-, and tri-O-digitoxoside derivatives of digitoxin and compared their activities to the corresponding MeON-neoglycosides. Both classes of cardenolide derivatives display comparable oligosaccharide chain length-dependent cytotoxicity toward human cancer cell lines. Further investigation revealed that both classes of compounds induce caspase-9-mediated apoptosis in non-small cell lung cancer cells (NCI-H460). Because O-glycosides and MeON-neoglycosides share a similar mode of action, the convenience of MeON-neoglycosylation could be exploited in future SAR work to rapidly survey large numbers of carbohydrates to prioritize selected O-glycoside candidates for traditional synthesis.

De novo approach to 2-deoxy-β-glycosides: Asymmetric syntheses of digoxose and digitoxin

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.

A stereoselective synthesis of digitoxin and digitoxigen mono- and bisdigitoxoside from digitoxigenin via a palladium-catalyzed glycosylation

(Chemical Equation Presented) A convergent and stereocontrolled route to trisaccharide natural product digitoxin has been developed. The route is amenable to the preparation of both the digitoxigen mono- and bisdigitoxoside. This route featured the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The natural product digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran.

Thermal Degradation of Glycosides, VI - Hydrothermolysis of Cardenolide and Flavonoid Glycosides

The hydrothermolysis of cardenolide and flavonoid glycosides is described.On heating with water or water/dioxane, cardenolide (1, 5, 11) and flavonoid glycosides (16, 20, 23, 27) are converted into their genuine aglycones and partially hydrolyzed products, together with saccharide components.Meanwhile, the glycosidic linkage of 2-deoxy sugar moieties in cardenolide glycosides is more readily cleaved than that of the common sugar moieties by means of hydrothermolysis.Therefore, hydrothermolysis of the uzarigenin triglycoside (13), bearing a 2-deoxy sugar moiety whichis directly attached to the aglycone, leads to selective cleavage of the sugar-aglycone linkage.The hydrothermolyzed products have been isolated by chromatography and their structures elucidated by spectroscopic methods. Key Words: Thermolysis / Degradation, thermal / Carbohydrates / Glycosides / Cardenolides / Steroids / Flavonoids

THERMAL TRANSFORMATION OF CARDIAC GLYCOSIDES II. ACIDLESS HYDROLYSIS OF LABILE GLYCOSIDES IN AQUEOUS ALCOHOLIC SOLUTIONS AND PROSPECTS FOR ITS UTILIZATION

The thermal transformations of cardiac glycosides in neutral alcoholic solutions have been investigated.The kinetics of their acidless hydrolysis at 100 and 142 deg C and the activation energy of the process have been studied.The possibility has been shown of the stepwise hydrolysis of natural trisdigitoxosides with the production of difficulty available mono- and bisdigitoxosides.The following were used as the objects of investigation: convallatoxin, glucostrophanthidin, cheirotoxin, desglucocheirotoxin, erycordin, erysimin, erysimoside, digitoxin, and cymarin.