Synthesis and characterization of 4,6-O-butylidene-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine: crystal structures of 4,6-O-butylidene-alpha-D-glucopyranose, 4,6-O-butylidene-beta-D-glucopyranosylamine and 4,6-O-butylidene-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine

4,6-O-Butylidene-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine was synthesized and characterized using analytical, spectral and single-crystal X-ray diffraction methods. 1H and 13C NMR studies showed the presence of the beta-anomer, which has also been confirmed by the crystal structure. The molecular structure of this compound showed the presence of the tridentate ONO ligation-core. Both precursors, 4,6-O-butylidene-alpha-D-glucopyranose and 4,6-O-butylidene-beta-D-glucopyranosylamine were characterized using single crystal X-ray diffraction. The alpha-anomeric nature of the former and beta-anomeric nature of the latter were proposed based on 1H NMR studies and were confirmed by determining the crystal structures. In addition, the crystal structure of 4,6-O-butylidene-beta-D-glucopyranosylamine revealed the C-1-N-glycosylation. In all the three molecules, the saccharide unit exhibits a 4C(1) chair conformation. In the lattice, the molecules are connected by hydrogen-bond interactions. The conformation of 4,6-O-butylidene-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine is stabilized via an O-H...N intramolecular interaction, and each molecule in the lattice interacts with three neighboring molecules through hydrogen bonds of the type O-H...O and C-H...O.     

Preparation of methyl 2,3-di-O-mesyl-4,6-thioanhydro-alpha-D-galactopyranoside and methyl 2-O-mesyl-4,6-thioanhydro-alpha-D-gulopyranoside

Two 2-oxa-7-thiabicyclo[4.2.0]octane derivatives, 4 and 10, with the D-galacto and D-gulo configuration, respectively, were obtained from methyl alpha-D-glucopyranoside. The thietane cyclization involved a thio-Mitsunobu reaction resulting in a 6-thioacetate, which underwent selective base-catalyzed intramolecular nucleophilic substitution at a C-4 mesylate. The structures of 4 and 10 were elucidated by X-ray diffraction analysis.     

A facile synthesis of 4,6-O-benzylidene-D-glycals via 1,5-anhydro-4,6-O-benzylidene-D-hex-1-en-3-ulose

Benzylidenation of readily available 1,5-anhydro-d-hex-1-en-3-ulose, followed by sodium borohydride reduction, afforded the title compounds in high yields. Separation of 4,6-O-benzylidene-d-allal and -d-glucal was accomplished by selective acetylation with lipase PS.     

Regioselective glycosylation of 4,6-O-benzylidenated glucopyranosides

Regioselective glycosylation with allyl 4,6-O-benzylidene-alpha,beta-D-glucopyranoside or methyl 4,6-O-benzylidene-alpha,beta-D-glucopyranoside as the acceptor was investigated. It was found that the regioselectivity depends upon donor size and anomeric configuration of the acceptor, i.e., with a monosaccharide donor and an alpha-form acceptor, the (1-->3)-linked product was obtained predominantly or exclusively, while with disaccharide or trisaccharide donors and either an alpha or beta form acceptor, the (1-->2)-linked oligosaccharides were the only products.     

Inhibition of sweet taste in humans by methyl 4,6-dichloro-4,6-dideoxy-{alpha}-D-galactopyranoside

The glycoside methyl 4,6-dichloro–4,6-dideoxy--D-galactopyranoside,an inhibitor of electrophysiological responses to sweet tastein gerbils, was also found to suppress the perceived intensitiesof various sweeteners in human psychophysical experiments. Incontrast, this compound did not suppress the salty and sourtastes in either species.     

An assay for GDP-D-mannose-4,6-dehydratase

The mechanism of GDP-D-mannose-4,6-dehydratase action with respect to loss of the C5 hydrogen has been established using GDP-D-[5-3H]-mannose as a substrate. This observation has been incorporated into a rapid assay for the enzyme based on the equilibration of 3H with the aqueous medium.     

O-ethylidene-D-allopyranoses: 1,2-O-,1,2:4,6-, and 2,3:4,6-di-O-ethylidene derivatives

Solutions of 1,2-O-acetoxonium chlorides derived from O-acetylated D-allopyranose derivatives were treated with sodium borohydride to give three pairs of previously unknown 1,2-O-ethylidene-α-D-allopyranose diastereoisomers: 3,4,6-tri-O-acetyl-1,2-O-ethylidene-α-D-allopyranoses; 4,6-di-O-acetyl-3-O-benzyl-1,2-O-ethylidene-α-D-allopyranoses; and 3-O-benzyl-1,2:4,6-di-O-ethylidene-α-D-allopyranoses. Examples of a second class of novel O-ethylidene-D-allopyranoses, the diastereoisomeric methyl 2,3:4,6-di-O-ethylidene-α-D-allopyranosides, were prepared by treating methyl 4,6-O-benzylidene-α-D-alloside with acetaldehyde-sulfuric acid. Assignments of dioxolane ring configurations and pyranose conformations were made by n.m.r. analyses.     

Syntheses of 4,6'-epoxymorphinan derivatives and their pharmacologies

A modification of the message site in the skeleton of naltrexone was carried out to improve the potency and selectivity of the compound for an opioid receptor subtype. In the course of conversion, we synthesized 7-membered ring ether derivatives, which had an inserted OCH(2) group between 4- and 6-positions of morphinan skeleton. One of the 7-membered ring ether derivatives possessed more potent antagonistic activity than naltrexone for the mu opioid receptor. Another compound possessing 17-methyl group derived from noroxycodone may be a mu opioid receptor partial agonist and showed analgesic activity. We are currently examining the subtype selectivity of these compounds.     

Synthesis of 2,3:4,6-di-O-isopropylidene-D-allopyranose from D-glucose

2,3:4,6-Di-O-isopropylidene-d-allopyranose can be conveniently prepared from d-glucose via a synthetic sequence, which includes Mitsunobu inversion at O-3, di-O-isopropylidenation of phenyl-1-thio-d-alloside and anomeric deprotection on treatment with NBS/CaCO3.     

Glycosylamines of 4,6-O-butylidene-alpha-D-glucopyranose: synthesis and characterization of glycosylamines, and the crystal structure of 4,6-O-butylidene-N-(o-chlorophenyl)-beta-D-glucopyranosylamine

A total of nine glycosylamines of 4,6-O-butylidene-alpha-D-glucopyranose were synthesized using primary amines having various groups in their ortho- or para-positions. Among these, six are monoglycosylamines, including one primary glycosylamine, and three are bis-glycosylamines. All these compounds were characterized by 1H, 1H-1H COSY, 1H-13C COSY and 13C NMR spectroscopy and FTIR spectra. The FAB mass spectra provided the molecular weights of the products by exhibiting the corresponding molecular ion peaks. The crystal structure of 4,6-O-butylidene-N-(o-chlorophenyl)-beta-D-glucopyranosylamine revealed the C-1 glycosylation, the beta-anomeric nature, and the 4C1 chair conformation of the saccharide unit in the product. In the lattice two types of dimers exist. While one type of dimer is formed through O-H...O type of interactions, the other type is formed via C-H...O type of interactions. In the direction of these C-H...O type of interactions, the dimeric units are connected to form a chain.