Inhibitors of endo-α-mannosidase. Part II. 1-Deoxy-3-O-(α-D-glucopyranosyl)-mannojirimycin and congeners modified in the mannojirimycin unit

Autor:	Ulrike Spohr, Robert G. Spiro, Mimi Bach
Rok vydání:	1993
Předmět:	Mannosidase chemistry.chemical_classification Stereochemistry Hydrogen bond Chemical shift Organic Chemistry Disaccharide General Chemistry Nuclear Overhauser effect Nuclear magnetic resonance spectroscopy Catalysis chemistry.chemical_compound chemistry Aldose Hydrolase
Zdroj:	Canadian Journal of Chemistry. 71:1928-1942
ISSN:	1480-3291 0008-4042
DOI:	10.1139/v93-240
Popis:	The syntheses of 1-deoxy-3-O-(α-D-glucopyranosyl)-mannojirimycin (9) and its 2-deoxy, 2-O-methyl, 4-deoxy, 4-O-methyl, 6-deoxy, 6-O-methyl, N-methyl, and N-propyl congeners are described. Since 9 was previously shown to effectively inhibit endo-α-D-mannosidase, a glycoprotein-processing hydrolase, these chemical modifications were designed to assist in the assessment of intermolecular hydrogen bonds of the inhibitor–enzyme complex. The previously reported data require that all hydroxyl groups of the deoxymannojirimycin unit of 9, namely, OH-2, OH-4, OH-6, and also the NH-5 group, interact with charged and polar groupings of the enzyme, since deoxygenations and alkylations abolished or significantly reduced activities. Conformational analysis of 9 and some of its congeners based on NMR chemical shifts, experimental and theoretical nuclear Overhauser enhancements, and HSEA calculations were performed. The chemical modifications of the glucose unit of 9 are described in the accompanying paper.
Databáze:	OpenAIRE
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