508-93-0

Usage

Uses

Used in Pharmaceutical Industry:
EVOMONOSIDE is used as an antitumor agent for its ability to inhibit tumor growth and progression. It is particularly effective against various types of cancer, offering a promising therapeutic option for cancer treatment.
Used in Cancer Research:
EVOMONOSIDE is used as a research tool for studying the mechanisms of tumor growth and progression. Its antitumor activity provides valuable insights into the development of novel cancer therapies and the understanding of cancer biology.

Upstream product

• 103368-07-6 (3β,5β,14β,17β)-3β-<(2,3,4-tri-O-benzyl-α-L-rhamnopyranosyl)oxy>-14-hydroxycard-20(22)-enolide 
• 86795-38-2 2,3,4-tri-O-(phenylmethyl)-α-L-rhamnopyranoside 
• 865484-73-7 tert-butyl ((2S,6S)-6-methyl-5-oxo-5,6-dihydro-2H-pyran-2-yl) carbonate 
• 1192-62-7 1-(2-furyl)-1-ethanone 
• 1256497-84-3 C₂₉H₄₀O₆ 
• 33156-32-0 C₂₉H₄₂O₆ 
• 247244-65-1 L-aculose 
• 4208-64-4 (S)-1-(2-furanyl)ethanol 
• 143-62-4 (+)-digitoxigenin 
• 161007-95-0 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyltrichloroacetimidate 
• 71-63-6 digitoxin 
• 14917-55-6 methyl 6-deoxy-α-L-mannopyranoside 
• 103368-09-8 2,3,4-tri-O-benzyl-β-L-rhamnopyranose 1-O-trichloroacetimidate 
• 103383-31-9 3,5-dinitro-2-pyridyl-2,3,4-tri-O-benzyl-α-L-rhamnopyranose 

Relevant academic research and scientific papers

Pregnanes That Bind to the Digitalis Receptor: Synthesis of 14-Hydroxy-5β,14β-pregnane Glycosides from Digitoxin and Digitoxigenin

The preparation of the mono-, bis-, and trisdigitoxosides of 14-hydroxy-5β,14β-pregnan-20-one and 14,20β-dihydroxy-5β,14β-pregnane by two routes, based on the conversion of the α,β-unsaturated γ-lactone in digitoxin to the 20-ketone and 20β-alcohol by ozonolysis and zinc-acetic acid treatment followed by lithium tri-tert-butoxyaluminum hydride reduction, are described.Synthesis of the α-L-rhamnoside derivatives is described also.Structures were confirmed by 1H and 13C NMR spectra.These derivatives show strong interaction with the cardiac glycoside receptor of heart muscle in an ouabain radioligand binding assay.Structure-activity relationships which are reported for glycosides and genins show that the α-L-rhamnoside derivatives are more potent than the β-D-digitoxoside or the β-D-glucoside and that the β-D-glucosides are more potent than the mono-, bis-, and trisdigitoxosides.Potency is not increased by the addition of the second and third digitoxose units.

Modular Total Synthesis and Cell-Based Anticancer Activity Evaluation of Ouabagenin and Other Cardiotonic Steroids with Varying Degrees of Oxygenation

A Cu(II)-catalyzed diastereoselective Michael/aldol cascade approach is used to accomplish concise total syntheses of cardiotonic steroids with varying degrees of oxygenation including cardenolides ouabagenin, sarmentologenin, 19-hydroxysarmentogenin, and 5-epi-panogenin. These syntheses enabled the subsequent structure activity relationship (SAR) studies on 37 synthetic and natural steroids to elucidate the effect of oxygenation, stereochemistry, C3-glycosylation, and C17-heterocyclic ring. Based on this parallel evaluation of synthetic and natural steroids and their derivatives, glycosylated steroids cannogenol-l-α-rhamnoside (79a), strophanthidol-l-α-rhamnoside (92), and digitoxigenin-l-α-rhamnoside (97) were identified as the most potent steroids demonstrating broad anticancer activity at 10-100 nM concentrations and selectivity (nontoxic at 3 μM against NIH-3T3, MEF, and developing fish embryos). Further analyses indicate that these molecules show a general mode of anticancer activity involving DNA-damage upregulation that subsequently induces apoptosis.

GLYCOSYLATED CARDIOTONIC STEROIDS

Compounds which are glycosylates of an A-ring of a cardiotonic steroid, wherein the steroid is attached to the anomeric position of (a) a monosaccharide comprising a C-4 amino group, or (b) an oligosaccharide are provided.

Synthesis and evaluation of the α- D -/α-l-rhamnosyl and amicetosyl digitoxigenin oligomers as antitumor agents

A highly regio- and stereoselective asymmetric synthesis of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation followed by bis-/tris-dihydroxylation or bis-/tris-diimide reduction. The α-l-rhamnose and α-l-amicetose digitoxin monosaccharide analogues displayed stronger apoptosis inducing activity and cytotoxicity against nonsmall cell human lung cancer cells (NCI-H460) than its d-diastereomeric isomers in a sugar-chain length dependent manner.

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.

C5′-alkyl substitution effects on digitoxigenin α-l-glycoside cancer cytotoxicity

A highly regio- and stereoselective asymmetric synthesis of various C5′-alkyl side chains of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation with postglycosylated dihydroxylation or diimide reduction. The C5′-methyl group in both α-l-rhamnose and α-l-amicetose digitoxin analogues displayed a steric directed apoptosis induction and tumor growth inhibition against nonsmall cell human lung cancer cells (NCI-H460). The antitumor activity is significantly reduced when the steric hindrance is increased at the C5′-stereocenter.

Synthesis of 20-hydroxy-, 20-amino-, and 20-nitro-14-hydroxy-21-nor- 5β,14β-pregnane C-3 glycosides and related derivatives: Structure-activity relationships of pregnanes that bind to the digitalis receptor

The preparation of derivatives of 14-hydroxy-21-nor-5β,14β-pregnane and 5β,14β-pregnane C-3 α-L-rhamnosides and tris-β-D-digitoxosides is described. These derivatives, possessing a C-17β COCH2OH, CH2OH, CO2H, CO2Me, CH2NH2, or CH2NO2 group, bind to the digitalis receptor recognition site of heart muscle as measured in a radioligand binding assay. The 21-norpregnane derivatives consistently show greater binding affinity than the corresponding 20α- and 20β-pregnane analogs. The C-20 nitro rhamnoside is comparable to digitoxin in binding affinity. The 17β-CH2NO2 group is the most effective replacement for the unsaturated lactone in the binding assay found so far, showing binding affinity comparable to that of the cardiac glycosides.

Cardiac Glycosides. 7. Sugar Stereochemistry and Cardiac Glycoside Activity

Digitoxigenin α-L, β-L, α-D, and β-D-glucosides; α-L-, β-L-, α-D-, and β-D-mannosides; and α-L- and β-L-rhamnosides were stereoselectively synthetized from the corresponding sugar tetrabenzyl trichloroacetimidates.The Na+, K+-ATPase receptor inhibitory activities of these glycosides (as a measure of receptor binding) were compared with those digitoxigenin, digitoxigenin 6'-hydroxy-β-D-digitoxide, digitoxigenin β-D-galactoside, and digitoxigenin β-D-digitoxoside.The observed activities reveal that a given sugar substituent may have a role in bindingof some glycoside stereoisomers, but not others.With α-L- and possibly β-L-rhamnosides, the 5'-CH3 and 4'-OH appear to have a predominant role in binding to the N+, K+-ATPase receptor.Addition of a 6'-OH to form the corresponding mannosides dramatically disrupts the effect of both the 5'-CH3 and 4'-OH in prompting receptor binding of the α-L isomer.However, with the β-L isomer, some influence of 4'-OH, 3'-OH, and 2'-OH binding remains.With β-D-glycosides, binding via the "5'-CH3 site" appears to be of little importance and addition of a 6'-OH diminishes activity only slightly.With these β-D-glycosides, and equatorial 4'-OH, axial 3'-OH, and equatorial 2'-OH groups appear to contribute to binding.