Glucuronoyl esterase is a novel carbohydrate esterase recently discovered in the cellulolytic system of the wood-rotting fungus Schizophyllum commune on the basis of its ability to hydrolyze methyl ester of 4-O-methyl-D-glucuronic acid. This substrate was not fully corresponding to the anticipated function of the enzyme to hydrolyze esters between xylan-bound 4-O-methyl-D-glucuronic acid and lignin alcohols occurring in plant cell walls. In this work we showed that the enzyme was capable of hydrolyzing two synthetic compounds that mimic the ester linkages described in lignin-carbohydrate complexes, esters of 4-O-methyl-D-glucuronic and D-glucuronic acid with 3-(4-methoxyphenyl)propyl alcohol. A comparison of kinetics of hydrolysis of methyl and 3-(4-methoxyphenyl)propyl esters indicated that the glucuronoyl esterase recognizes the uronic acid part of the substrates better than the alcohol type. The catalytic efficiency of the enzyme was much higher with the ester of 4-O-methyl-D-glucuronic acid than with that of D-glucuronic acid. Examination of the action of glucuronoyl esterase on a series of methyl esters of 4-O-methyl-D-glucopyranuronosyl residues alpha-1,2-linked to xylose and several xylooligosaccharides suggested that the rate of deesterification is independent of the character of the carbohydrate part glycosylated by the 4-O-methyl-D-glucuronic acid.

Inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus influences progress of tumor growth and metastasis. Golgi α-mannosidase II (GMII) has become a therapeutic target for drugs with anticancer activities. One critical task for successful application of GMII drugs in medical treatments is to decrease their unwanted co-inhibition of lysosomal α-mannosidase (LMan), a weakness of all known potent GMII inhibitors. A series of novel N-substituted polyhydroxypyrrolidines was synthesized and tested with modeled GH38 α-mannosidases from Drosophila melanogaster (GMIIb and LManII). The most potent structures inhibited GMIIb (K =50-76 μm, as determined by enzyme assays) with a significant selectivity index of IC (LManII)/IC (GMIIb) >100. These compounds also showed inhibitory activities in in vitro assays with cancer cell lines (leukemia, IC =92-200 μm) and low cytotoxic activities in normal fibroblast cell lines (IC >200 μm). In addition, they did not show any significant inhibitory activity toward GH47 Aspergillus saitoiα1,2-mannosidase. An appropriate stereo configuration of hydroxymethyl and benzyl functional groups on the pyrrolidine ring of the inhibitor may lead to an inhibitor with the required selectivity for the active site of a target α-mannosidase.

The reaction of silylated nucleophiles with 6,1-anhydroglucopyranuronic acid (glucuronic acid 6,1-lactones) catalysed by tin(IV) chloride provides 1,2-trans or 1,2-cis (deoxy)glycosides in a manner dependent on the donor structure. The alpha-glycoside was obtained for reactions of the donor with the 2-acyl group and 2-deoxydonors, whereas the 2-deoxy-2-iodo donor gave the beta-glycoside. Experimental evidence shows that when 1,2-cis-glycoside formation occurs, the anomerisation of initially formed 1,2-trans-glycosides catalysed by SnCl(4) is possible. The anomerisation of beta-D-glucopyranosiduronic acids was found to be faster, in some cases, than anomerisation of related beta-D-glucopyranosiduronic acid esters and beta-D-glucopyranoside derivatives and the rates are dependent on the structure of the aglycon. Moreover, the rates of anomerisation of beta-D-glucopyranuronic acid derivatives can be qualitatively correlated with rates of hydrolysis of beta-D-glucopyranosiduronic acids. Mechanistic possibilities for the reactions are considered.

β‐(1→2)‐Linked oligomannosides constitute an important class of carbohydrate structures located on the cell surface of several Candida species, including C. albicans. As a result of the immunostimulating properties of such compounds, the upscaling of their synthesis is relevant. In this paper, a highly stereoselective synthesis of β‐(1→2)‐linked oligomannosides was performed by further development of and modifications to the methodologies described earlier in the literature. In addition to the synthesis of fully deprotected β‐(1→2)‐linked mannobiose and mannotriose, some preliminary modifications to the oligosaccharide core, resulting in close analogues with biological potential, are presented. The fully deprotected products form potential targets for screening against C. albicans and may also result in new model structures for vaccine development.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Three new triazole conjugates derived from D-mannose were synthesized and assayed in in vitro assays to investigate their ability to inhibit α-mannosidase enzymes from the glycoside hydrolase (GH) families 38 and 47. The triazole conjugates were more selective for a GH47 α-mannosidase (Aspergillus saitoi α1,2-mannosidase), showing inhibition at the micromolar level (IC 50 values of 50-250 μM), and less potent towards GH38 mannosidases (IC 50 values in the range of 0.5-6 mM towards jack bean α-mannosidase or Drosophila melanogaster lysosomal and Golgi α-mannosidases). The highest selectivity ratio [IC 50 (GH38)/IC 50 (GH47)] of 100 was exhibited by the triazole conjugate 6. To understand structure-activity properties of synthesized compounds, 3-D complexes of inhibitors with α-mannosidases were built using molecular docking calculations.

Stereoselective glycoside synthesis is of interest because of the biological and medical relevance of oligosaccharides, glycoproteins, glycolipids, [1] and other carbohydrate derivatives, [2] and a range of strategies have been developed to produce these compounds.[3] The 1,6-lactone derivative 2 (see Scheme 1) has potential for use in the synthesis of 1,2-cisglycosides [4] but its application has been limited because of the low yields obtained from its reaction with alcohols.[5] We now report that the SnCl 4 -catalyzed coupling of silyl ethers [6] with 2 provides a-O-glucuronides in significantly improved yields without loss of stereoselectivity. The methodology has been extended to the related 2-deoxylactones, which give aor b-glycosides depending on the structure of the donor.The preparation of 2 was carried out via the mixed anhydride 1 (Scheme 1) by an improved and shorter procedure than that previously described.[5] The donors 6 and 7 were also prepared, via glycal 4, because of their potential for the synthesis of 2-deoxyglycosides, which are of biological interest.[7] Thus, the reaction of the allyl ester 3 with hydrogen bromide in acetic acid gave a glycosyl bromide intermediate

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