Synthesis, Characterization, in Silico Optimization, and Conformational Studies of Methyl 4-O-PIVALOYL-Α-L-RHAMNOPYRANOSIDES (original) (raw)
Related papers
In Silico Biological Profile Prediction of Some Selectively Synthesized Acyl Rhamnopyranosides
Journal of Scientific Research, 2021
Over the past several decades significant biological activities including brains protective and antimicrobial activities have made sugar esters (SEs) as a topic of great interest. In this context, unimolar 3-chlorobenzoylation of methyl α-L-rhamnopyranoside (4) using dibutyltin oxide method regioselectively furnished only the 3-O-substitution product 5 in excellent yield. The reaction proceeded via the formation of a cyclic 2,3-Odibutylstannylene intermediate where equatorial hydroxyl group is activated by the tin atom leading to the formation of product 5 only. To get biologically important rhamnopyranoside esters chlorobenzoate 5 was further converted into three newer 2,4-di-O-acyl products 6-9 with other acylating agents using direct acylation method. Prediction of activity spectra for substances (PASS) indicated that these rhamnopyranoside esters have many promising biological profiles including CYP2H substrate, membrane permeability inhibitor and better antifungal activities. Additionally, ADMET and drug likeness properties of SEs 5-8 were predicted and discussed.
Structural analysis of methyl α-l-rhamnopyranoside in the solid state
Carbohydrate Research, 1994
Methyl cu-L-rhamnopyranoside [l] (1, methyl 6-deoxy-cY+mannopyranoside), usually obtained by heating L-rhamnose monohydrate in acidic methanol, is an important synthetic intermediate and a partial structure of a growing family of pyranonaphthoquinone (benzoisochromanquinone) antibiotics such as nanaomycin D [2], kalafungin [3], granaticin [4] and medermycin [51 that have been shown to possess significant antimicrobial activities and potential antitumor activities 161.
Molecules
The most widely used and accessible monosaccharides have a number of stereogenic centers that have been hydroxylated and are challenging to chemically separate. As a result, the task of regioselective derivatization of such structures is particularly difficult. Considering this fact and to get novel rhamnopyranoside-based esters, DMAP-catalyzed di-O-stearoylation of methyl α-l-rhamnopyranoside (3) produced a mixture of 2,3-di-O- (4) and 3,4-di-O-stearates (5) (ratio 2:3) indicating the reactivity of the hydroxylated stereogenic centers of rhamnopyranoside as 3-OH > 4-OH > 2-OH. To get novel biologically active rhamnose esters, di-O-stearates 4 and 5 were converted into six 4-O- and 2-O-esters 6–11, which were fully characterized by FT-IR, 1H, and 13C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides 6–11 with maximum lipophilic character showed better antifungal susceptibility than antibacterial activity. These experimental...
International Journal of Molecular Sciences, 2016
Benzyl α-L-rhamnopyranoside 4, obtained by both conventional and microwave assisted glycosidation techniques, was subjected to 2,3-O-isopropylidene protection to yield compound 5 which on benzoylation and subsequent deprotection of isopropylidene group gave the desired 4-O-benzoylrhamnopyranoside 7 in reasonable yield. Di-O-acetyl derivative of benzoate 7 was prepared to get newer rhamnopyranoside. The structure activity relationship (SAR) of the designed compounds was performed along with the prediction of activity spectra for substances (PASS) training set. Experimental studies based on antimicrobial activities verified the predictions obtained by the PASS software. Protected rhamnopyranosides 5 and 6 exhibited slight distortion from regular 1 C 4 conformation, probably due to the fusion of pyranose and isopropylidene ring. Synthesized rhamnopyranosides 4-8 were employed as test chemicals for in vitro antimicrobial evaluation against eight human pathogenic bacteria and two fungi. Antimicrobial and SAR study showed that the rhamnopyranosides were prone against fungal organisms as compared to that of the bacterial pathogens. Interestingly, PASS prediction of the rhamnopyranoside derivatives 4-8 were 0.49 < P a < 0.60 (where P a is probability 'to be active') as antibacterial and 0.65 < P a < 0.73 as antifungal activities, which showed significant agreement with experimental data, suggesting rhamnopyranoside derivatives 4-8 were more active against pathogenic fungi as compared to human pathogenic bacteria thus, there is a more than 50% chance that the rhamnopyranoside derivative structures 4-8 have not been reported with antimicrobial activity, making it a possible valuable lead compound.
Regioselective Synthesis of Some Rhamnopyranoside Esters for PASS Predication, and ADMET Studies
Journal of the Turkish Chemical Society Section A: Chemistry, 2021
Notable biological activities including brains protective activities have made carbohydrate esters as a topic of great interest over the past several decades. In this context, unimolecular treatment of methyl α-L-rhamnopyranoside with dibutyltin oxide gave the corresponding 2,3-O-(dibutylstannylene) derivative which was then allowed to react with 3-chlorobenzoyl chloride. The reaction regioselectively furnished the 3-O-substitution product in excellent yield. To get newer rhamnopyranoside esters chlorobenzoate was further converted into four 2,4-di-O-substituted products with other acylating agents using direct acylation technique. Moreover, thermodynamic properties indicated that these sugar esters (SEs) possess better stability, suitable polar nature and higher binding affinity than the non-ester rhamnopyranoside. Prediction of Activity Spectra for Substances (PASS) predication showed that these SEs should be more potent against fungal pathogens than the bacterial organisms. With these encouraging results absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of the SEs are also discussed.
Carbohydrate Research, 1983
Benzyl 3-O-benzoyl-4-O-benzyl-2-0-(2,3,6-trideoxy-cu-L-g~ycera-hex-2-enopyranosyl-4-ulose)-a-L-rhamnopyranoside has been investigated by X-ray diffraction methods. The crystals obtained from aqueous ethanol are orthorhombic, space group P212121 with cell constants u = l&775(2), b = 10.857(2), and c = 25.774(3) A. A four-circle, automatic diffractometer was used for intensity-data collection. Out of 3370 reflection intensities, 2634 were of I > 20, and these were used for refinement. The structure was solved by direct methods, and the atomic parameters were then refined by the full-matrix, least-squares procedure. The unsaturated dihydropyranone ring adopts a deformed sofa conformation, whereas the rhamnopyranose ring adopts a chair conformation. The glycosidic linkage is characterised by torsion angles @33(2)" and ly -13( 1)". A new classification for the conformations of glycosidic linkages is suggested. 0008-6215/83/$03.00 0 1983 Elsevier Science Pubhshers B.V.
Naturally Occurring Rhamnopyranosides as Anticancer Agents: Molecular Docking and ADMET Study
Journal of Applied Science & Process Engineering
After heart disease, cancer continues to be the second most prevalent cause of death in the USA. Several chemotherapeutic treatments (drugs) are available for cancer that use powerful chemicals to kill the body's rapidly proliferating cells. However, recent research disclosed that many clinically viable anticancer drugs have been developed with the help of chemicals originating from plants. A number of phytochemicals isolated from plants possess rhamnopyranoses and some of them are acyl rhamnopyranoses. Encouragingly, such compounds were reported for their cell proliferation and migration inhibition activities against invasive human triple-negative breast cancer cells. In this study, four naturally occurring rhamnopyranose esters were checked against three cancer-related proteins (PDB IDs: 3TJM, 4OAR, and 5FGK) via molecular docking. Rhamnose compounds 3-6 showed better binding energy compared to the related standard drugs in use in the hospitals. Compound 6 was found highly pot...
Carbohydrate Research, 1985
Both diastereoisomers of 1-phenylethylidene acetals (acetophenone acetals) of methyl and benzyl P-L-arabinopyranoside and a-L-rhamnopyranoside were prepared. Acetal-exchange reactions gave only the endo-phenyl isomers; their 2-0and 4-0-acetyl derivatives were isomerised into the exe-phenyl compounds.'H-N.m.r. data were used to determine the absolute configuration at the acetal carbon atom in these compounds. The protons of the methyl group of the exe-phenyl isomers resonate at lower field than those of the endo-phenyl isomers. Hydrogenolysis of various methylene, ethylidene, and isopropylidene derivatives gave axial ethers. The endo-phenyl isomers of the acetophenone derivatives also gave axial l-phenylethyl ethers in two diastereoisomeric forms. The exe-phenyl isomers of the arabinosides were stable towards the reagent (LiAlH,-AlCl,), whereas the corresponding rhamnopyranosides gave the 2-(1-phenylethyl) ethers, but cleavage required prolonged reaction time and higher temperature.
Antimicrobial evaluation of methyl 4-O-Acetyl-α-L-Rhamnopyranoside derivatives
Chittagong University Journal of Biological Sciences, 2013
A number of 2,3-di-O-acyl derivatives (6-11) of methyl 4-O-acetyl-a-Lrhamnopyranoside (5) obtained by using various acylating agents were screened for in vitro antifungal activity against four plant pathogenic fungi, viz., Alternaria alternata, Curvularia lunata. Fusarium equiseti and Macrophomina phaseolina. These compounds were also screened for in vitro antibacterial activity against ten human pathogenic bacteria, viz., Bacillus subtilis, Bacillus cereus, Bacillus megaterium, Staphylococcus aureus, Escherichia coli, INABA ET (Vibrio), Pseudomonas species, Salmonella paratyphi, Shigella dysenteriae and Salmonella typhi. The study reveal that these 4-O-acetyl-?-L-rhamnopyranoside derivatives are more prone towards antifungal activities than that of antibacterial activities. DOI: http://dx.doi.org/10.3329/cujbs.v3i1.13404 The Chittagong Univ. J. B. Sci.,Vol. 3(1&2):33-43, 2008