Significant rate accelerated synthesis of glycosyl azides and glycosyl 1,2,3-triazole conjugates

An efficient and significantly rapid access of a series of glycosyl azides and glycosyl 1,2,3-triazole conjugates is reported using modified one-pot reaction conditions. In both cases yields were excellent and single diastereomers were obtained. Figure Rapid preparation of 4-substituted glycosyl 1,2,3-triazole conjugates from glycosyl bromides. CDRI communication no. 7340.     

2'-Carboxybenzyl glycosides: glycosyl donors for C-glycosylation and conversion into other glycosyl donors

Glycosylation of various glycosyl acceptors with 2'-carboxybenzyl (CB) 2,3,4,6-tetra-O-benzyl-beta-D-glucopyranoside and CB 2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranoside as glycosyl donors afforded alpha-C-glycosides exclusively or predominantly in good yields. CB glycosides were also converted to other well-known glycosyl donors, the corresponding phenyl thioglycoside and the glycosyl fluoride derivatives.     

Synthesis and mesogenic properties of glycosyl diacylglycerols

We synthesised glycosyl diacylglycerols bearing unsaturated or chiral methyl branched fatty acid chains. The thermotropism was measured with polarising microscopy and additionally the lyotropism with the contact preparation method. The synthesised compounds displayed thermotropic S(A) (lamellar), cubic and columnar phases and investigation of the lyotropic phase behaviour led to the observation of inverted bicontinuous cubic V(II) phases, lamellar L(alpha) phases and normal bicontinuous cubic V(I) phases. The phases are discussed with respect to the chemical structures that have been varied systematically to derive structure--property relationships.     

Appel-Lee synthesis of glycosyl inositols, substrates for inositol dehydrogenase from Bacillus subtilis

We recently reported that inositol dehydrogenase (EC 1.1.1.18) from Bacillus subtilis can catalyze the highly stereoselective oxidation of 1l-4-O-substituted myo-inositol derivatives, as well as disaccharides melibiose and isomaltose, but not gentiobiose or maltose, consistent with the requirement of an alpha-(1-->6) linkage. We believed that the enzyme might therefore catalyze efficient stereoselective oxidation of the appropriate alpha-linked glycosyl inositols. We have synthesized alpha-D-glucopyranosyl-(1-->4)-(DL)-myo-inositol and alpha-d-galactopyranosyl-(1-->4)-(DL)-myo-inositol using the Appel-Lee protocol to couple benzyl-protected glycosyl donors to protected inositols. This method failed in our hands using glycosyl donors derived from D-mannose and 2-azido-2-deoxy-D-glucose. When myo-inositol 1,3,5-monoorthoformate is used as the acceptor, the reaction is regiospecific for the 4/6-position. We report here the mildest conditions known for the removal of the orthoformate group. 2-Azido-2-deoxy-alpha-D-glucopyranosyl-(1-->4)-(DL)-myo-inositol was synthesized using the trichloroacetimidate derivative as the donor, and all three pseudo-disaccharides were substrates for inositol dehydrogenase. The glucopyranosyl and galactopyranosyl derivatives displayed apparent second-order rate constants comparable to that of myo-inositol.     

Synthesis and evaluation of antitubercular activity of glycosyl thio- and sulfonyl acetamide derivatives

A series of glycosyl thioacetamide and glycosyl sulfonyl acetamide derivatives have been prepared following a convenient reaction protocol and evaluated for their antitubercular activity against Mycobacterium tuberculosis H₃₇Rv. Amongst 32 compounds evaluated 3 compounds were effective in inhibiting mycobacterial growth at MIC of 6.25 μg/mL, 6 compounds at MIC of 3.125 μg/mL and 1 compound at MIC of 1.56 μg/mL. All active compounds were found nontoxic in Vero cell lines and mice bone marrow macrophages.     

Aryl C-glycosylation of phenols with glycosyl trifluoroacetimidates

Aryl C-glycosylation of a variety of phenols with glycosyl trifluoroacetimidates in the presence of TMSOTf was examined, leading to the corresponding ortho-hydroxyaryl C-glycosides in variable yields.     

Molecular design, synthesis and bioactivity of glycosyl hydrazine and hydrazone derivatives: notable effects of the sugar moiety

Assuming that the water solubility of our previous hydrazone derivatives would improve after modification with sugars while keeping or modulating their notable biological activities, we designed and synthesized some glycosyl hydrazine and hydrazone derivatives. Bioassay results indicated that the antitumor activity of our previously prepared hydrazones reduced or disappeared after modification with sugars. On the contrary, some glycosyl derivatives displayed much better antifungal activity against selected fungi. Obviously, a small sugar can change the biological activity of hydrazones significantly.     

Ritter-based glycoconjugation of amino acids and peptides--access to novel glycoconjugates displaying a beta-amide linkage between amino acid and sugar moiety

Beta-peptidic-D-gluco-, D-galacto-, and L-fuco-configured glycosyl amino acids can be prepared from the corresponding 2-deoxy-oct-3-ulopyranosonic acids via a one-pot intramolecular Ritter reaction. Initially, a ketopyranoside-based acid condenses under Lewis acid promoted conditions with nitriles (PhCN, MeCN) and a partially protected diamino ester (Boc-DAB-O-t-Bu, Boc-Orn-O-t-Bu) to form a beta-peptidic glycosyl amino t-butylesters. The glycosyl amino t-butylesters can be converted into Fmoc-protected glycosyl amino acids that are suitably protected for solid-phase glycopeptide synthesis. Furthermore, replacement of the protected diamino ester by immobilized peptide amines permits post-synthetic N-terminal- and N(epsilon)-glycoconjugation of peptides on the solid phase.     

Mild one-pot preparation of glycosyl bromides

Mild one-pot protocols for the preparation of glycosyl bromides and alkyl bromides via in situ generation of HBr is reported here.     

Stereoselective synthesis of 1,2-cis- and 2-deoxyglycofuranosyl azides from glycosyl halides

Protected 1,2-cis glycofuranosyl azides with alpha-D-ribo, beta-D-arabino and 2-deoxy-2-fluoro-beta-D-arabino configurations were efficiently prepared from the appropriate 1,2-trans glycosyl halides bearing non-participating 0-2 substituent by inversion with sodium azide under phase transfer catalytic conditions (80-85% yields, 90-96% de). The same method failed to result in sufficiently good beta-selectivity starting from 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-ery-thro-pentofuranosyl chloride (5alpha) (40% de). The selectivity in favour of the protected 2-deoxy-beta-D-erythro-pentofura-nosyl azides was greatly improved (74-80% de) by treating 5alpha and its p-chlorobenzoyl analog 6alpha with cesium or potassium azide in dimethylsulfoxide at room temperature (83-85% yields).     

Synthesis of glycosyl amino acids by light-induced coupling of photoreactive amino acids with glycosylamines and 1-C-aminomethyl glycosides

The glycosylamines of O-acetyl-protected GlcNAc and chitobiose, as well as two partially unprotected 1-C-aminomethyl glucosides, were photochemically coupled with orthogonally protected N-aspartyl-5-bromo-7-nitroindoline derivatives. The reactions proceeded under neutral conditions by irradiation with near-UV light. The glycosyl asparagines with N- or C-glycosyl linkages were afforded in 60-85% yield on a 10-70 mg scale. Moreover, the ability of a highly photoreactive N-glutamyl-4-methoxy-7-nitroindoline derivative to acylate amino saccharides was tested. Upon irradiation in the presence of a dimeric 1-C-aminomethyl glycoside, or a glycosylamine, the corresponding glycosyl glutamines were obtained in 50% and 30% yield, respectively. Preparations of the photoreactive aspartates and the 1-C-aminomethyl glycosides are also described.     

Design,synthesis and biological evaluation of azithromycin glycosyl derivatives as potential antibacterial agents

A series of 11,12-cyclic carbonate azithromycin-4″-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated as antibacterial agents to search for target compounds with excellent activity. The results of preliminary antibacterial tests against eight strains in vitro revealed that all of the title compounds exhibited improved activities with broad spectrum compared with the parent compound. The glycosylated side chains may be the pharmacophores responsible for the improved activity.     

An efficient and selective method for preparing glycosyl sulfoxides by oxidizing glycosyl sulfides with OXONE or t-BuOOH on SiO2

Silica gel adsorbed with OXONE or t-BuOOH was used as a mild oxidant to selectively oxidize glycosyl sulfides to corresponding sulfoxides in good yields and without sulfones formation. This method was also found compatible with various other functional groups in the glycosides.     

Zinc triflate-benzoyl bromide: a versatile reagent for the conversion of ether into benzoate protecting groups and ether glycosides into glycosyl bromides

A simple and efficient method is developed for the chemoselective one-pot conversion of ethers (benzyl, TBDMS and acetal) to the corresponding benzoates by zinc triflate-catalyzed deprotection and benzoylation by benzoyl bromide. In the same reaction, methyl or p-methoxyphenyl glycosides are converted into glycosyl bromides that are useful in glycosylation reactions.     

Syntheses of amphiphilic glycosylamides from glycosyl azides without transient reduction to glycosylamines

Protected glycosyl azides react with acyl chlorides in the presence of triphenylphosphine to afford glycosylamides in high yields, at room temperature. Starting from the beta-glycosyl azides, the reaction is highly stereoselective and occurs with retention of configuration, whereas the alpha-azido anomers display a lower stereoselectivity giving rise to alpha/beta mixtures of glycosylamides. The reaction was applied to several monosaccharidic azides and to lactosyl azide with various acyl chlorides; it was shown to be of general use for preparing 1,2-trans beta-glycosylamides.     

Glycosyl iodides. History and recent advances

The use of glycosyl iodides as an effective method for the preparation of glycosides has had a recent resurgence in carbohydrate chemistry, despite its early roots in which these species were believed to be of limited use. Renewed interest in these species as glycosylating agents has been spurred by their demonstrated utility in the stereoselective preparation of O-glycosides, and other glycosylic compounds. This review provides a brief historical account followed by an examination of the use of glycosyl iodides in the synthesis of oligosaccharides and other glycomimetics, including C-glycosylic compounds, glycosyl azides and N-glycosides.     

Synthesis of new glycosyl biuret and urea derivatives as potential glycoenzyme inhibitors

O-Peracetylated 1-(β-d-glucopyranosyl)-5-phenylbiuret was prepared in the reaction of O-peracetylated β-d-glucopyranosylisocyanate and phenylurea. The reaction of O-peracetylated N-β-d-glucopyranosylurea with phenylisocyanate furnished the corresponding 1-(β-d-glucopyranosyl)-3,5-diphenyl- as well as 3-(β-d-glucopyranosyl)-1,5-diphenyl biurets besides 1-(β-d-glucopyranosyl)-3-phenylurea. O-Peracetylated 1-(β-d-glucopyranosyl)-5-(β-d-glycopyranosyl)biurets were obtained in one-pot reactions of O-peracetylated β-d-glucopyranosylamine with OCNCOCl followed by a second glycopyranosylamine of β-d-gluco, β-d-galacto and β-d-xylo configurations. O-Acyl protected 1-(β-d-glucopyranosyl)-3-(β-d-glycopyranosylcarbonyl)ureas were obtained from the reaction of β-d-glucopyranosylisocyanate with C-(glycopyranosyl)formamides of β-d-gluco and β-d-galacto configurations. The O-acyl protecting groups were removed under acid- or base-catalyzed transesterification conditions, except for the N-acylurea derivatives where the cleavage of the N-acyl groups was faster than deprotection. Some of the new compounds exhibited moderate inhibition against rabbit muscle glycogen phosphorylase b and human salivary α-amylase.     

Mass spectrometric identification and quantification of glycosyl flavonoids, including dihydrochalcones with neutral loss scan mode

We developed a strategy for determination and quantification of glycosyl flavonoids using liquid chromatography-triple quadrupole mass spectrometry with neutral loss scan at 15 and 30eV collision energy in the positive ion mode. The fragmentation patterns of glycosyl flavonoids at 15 and 30eV showed that fragmentation of sugar moiety depended on the type of glycosidic bond to aglycone, the site of C-glycosylation, and the type of aglycone. C-Glycosyl dihydrochalcones especially stood out because they produced [M+H-162](+) even at 15eV such as O-glycoside in spite of C-glycoside. C-Glycosides were classified according to (i) the intensity ratio A of [M+H-150](+) to [M+H-120](+) at 30eV and (ii) the intensity ratio B of [M+H-120](+) at 15eV to one at 30eV. The 8-C-glycosides were A<1 and B<1, the 6-C-glycosides were A>1 and B<1, and the C-glycosyl dihydrochalcones were A>1 and B>1. Therefore, the intensity ratios of the neutral loss scan of 120 and 150Da at 30eV and those of 120, 162, and 308Da at 15eV allowed sequential distinction among these three types of C-glycosides as well as between O- and C-glycosides. Our method was applied for analysis of Rooibos tea, and the identified glycosides could be quantified specifically by the selected reaction monitoring method.     

Effect of carbodiimides on the activity of Mg(2+)-ATPase of slow-twitch muscle microsomal membranes.

1. The hydrophobic N,N'-dicyclohexylcarbodiimide (DCCD) inhibits the activity of Mg(2+)-ATPase of slow-twitch muscle microsomal fraction. 2. The inhibition is dependent on time and concentration, with half-maximal inhibition occurring at 0.4 mM concentration of carbodiimide after a 0.5 hr incubation at room temperature. 3. ATP does not protect against the inhibition. 4. Two water-soluble carbodiimides, 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide (CMCD) and 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDCD), are not inhibitory. 5. Inhibition of Mg(2+)-ATPase activity by DCCD is accompanied by covalent incorporation of the radioactive agent into the partially purified enzyme preparation.