A method for the chemoselective reduction of glycopyranosyl azides using SnCl4 and tin metal as the reducing agent followed by in situ chloroacetylation of the synthesized glycopyranosyl amine was developed. This reaction is applicable to diversely functionalized glycopyranosyl azides for the synthesis of glycopyranosyl chloroacetamides. © 2013 Elsevier Ltd. All rights reserved.

Laxminarayan Sahoo

Anadi Singhamahapatra

Katuri J V Paul

Duraikkannu Loganathan

Azide

CHLOROACETAMIDE

glucose derivative

ACETYLATION

article

isomer

reduction

synthesis

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Tetrahedron Letters

A conceptually novel strategy has been developed for the synthesis of N-(β-glycosyl)asparagine precursors in good yield by the alkylation of ethyl nitroacetate using six per-O-acetylated N-(β-glycosyl)iodoacetamides derived from mono- and disaccharides. The use of a chiral organocatalyst, N-(9-anthracenylmethyl)cinchoninium chloride (10 mol %), resulted in diastereoselective alkylation up to 64% de. Single crystal structure analysis of the purified major diastereomer of the Glc derivative revealed an absolute configuration of S at the α-carbon of the monosubstituted ethyl nitroacetate which is a precursor of the l-asparagine conjugate. © 2010 Elsevier Ltd. All rights reserved.

A novel strategy toward the synthesis of N-(β-glycosyl)asparagines based on the alkylation of ethyl nitroacetate using N-(β-glycosyl) iodoacetamides

A general and expedient method based on a click reaction has been developed for the synthesis of novel glycolipids. The Cu(I) catalyzed [3+2] cycloaddition of several fully acetylated β- as well as α-d-glycopyranosyl azides, including the 1,6-diazide derived from d-glucose, with long chain alkyl propargyl ethers gave the respective 1,4-substituted 1,2,3-triazole derivatives in good yields. Treatment of fully acetylated N-(β-glycopyranosyl)azidoacetamides under similar conditions with alkyl propargyl ethers afforded the 1,2,3-triazolylacetamido derivatives in fairly good yields. Zemplen de-O-acetylation of all the fully acetylated derivatives furnished the free glycolipids in quantitative yields. © 2008 Elsevier Ltd. All rights reserved.

Synthesis of novel glycolipids derived from glycopyranosyl azides and N-(β-glycopyranosyl)azidoacetamides

4-Phenyl-N-(β-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide (glucosyltriazolylacetamide) has been studied in kinetic and crystallographic experiments with glycogen phosphorylase b (GPb), in an effort to utilize its potential as a lead for the design of potent antihyperglycaemic agents. Docking and molecular dynamics (MD) calculations have been used to monitor more closely the binding modes in operation and compare the results with experiment. Kinetic experiments in the direction of glycogen synthesis showed that glucosyltriazolylacetamide is a better inhibitor (Ki = 0.18 mM) than the parent compound α-D-glucose (Ki = 1.7 mM) or β-D-glucose (Ki = 7.4 mM) but less potent inhibitor than the lead compound N-acetyl-β-D-glucopyranosylamine (Ki = 32 μM). To elucidate the molecular basis underlying the inhibition of the newly identified compound, we determined the structure of GPb in complex with glucosyltriazolylacetamide at 100 K to 1.88 Å resolution, and the structure of the compound in the free form. Glucosyltriazolylacetamide is accommodated in the catalytic site of the enzyme and the glucopyranose interacts in a manner similar to that observed in the GPb-α-D-glucose complex, while the substituent group in the β-posi tion of the C1 atom makes additional hydrogen bonding and van der Waals interactions to the protein. A bifurcated donor type hydrogen bonding involving O3H, N3, and N4 is seen as an important structural motif strengthening the binding of glucosyltriazolylacetamide with GP which necessitated change in the torsion about C8-N2 bond by about 62° going from its free to the complex form with GPb. On binding to GP, glucosyltriazolylacetamide induces significant conformational changes in the vicinity of this site. Specifically, the 280s loop (residues 282-288) shifts 0.7 to 3.1 Å (CA atoms) to accommodate glucosyltriazolylacetamide. These conformational changes do not lead to increased contacts between the inhibitor and the protein that would improve ligand binding compared with the lead compound. In the molecular modeling calculations, the GOLD docking runs with and without the crystallographic ordered cavity waters using the GoldScore scoring function, and without cavity waters using the ChemScore scoring function successfully reproduced the crystallographic binding conformation. However, the GLIDE docking calculations both with (GLIDE XP) and without (GLIDE SP and XP) the cavity water molecules were, impressively, further able to accurately reproduce the finer details of the GPb-glucosyltriazolylacetamide complex structure. The importance of cavity waters in flexible receptor MD calculations compared to "rigid" (docking) is analyzed and highlighted, while in the MD itself very little conformational flexibility of the glucosyltriazolylacetamide ligand was observed over the time scale of the simulations. © 2007 Wiley-Liss, Inc.

Proteins: Structure, Function and Genetics

Crystallographic and computational studies on 4-phenyl-N-(β-D- glucopyranosyl)-1H-1,2, 3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: Comparison with α-D-glucose, N-acetyl-β-D- glucopyranosylamine and N-benzoyl-N′-β-D-glucopyranosyl urea binding

Crystal structures of 1-N-(β-D-glucopyranosyl)chloroacetamide (1), an inhibitor of glycogen phosphorylase, and the corresponding galactopyranosyl amide (2) have been determined. Both crystals belong to P212 121 space group with 1 having the unit cell dimensions of a = 7.939(3), b = 9.547(3) and c = 14.157(2) Å, while those of 2 are, a = 7.636(10), b = 9.004(8) and c = 14.807(5) Å. The sugar ring takes a 4C1 conformation and the amide linkage exists in Z-anti conformation in both crystals. The torsion angle O5-C1-N1-C1′ is -93.9(5) for 1 and -111.5(3)° for 2. The conformational preference of Cl and N1 in 1 and 2 is found to be between anti and gauche. The molecular assembly in both 1 and 2 is stabilized by a finite chain of hydrogen bonds starting from N1H and ending at O1′, whereas a ten membered hydrogen-bonded ring involving O4H and O5 is observed in 1.

Journal	Tetrahedron Letters
ISSN	00404039
Open Access	No