Hiro Ohtake

An efficient synthesis of new 1′-C-methyl-α-O-disaccharides using 1-methylenesugars as the glycosyl donors

A series of new 1′-C-methyl-α-disaccharides were firstly synthesized by the directly Lewis acid-catalyzed O-glycosidation of 1-methylenesugars used as glycosyl donors. The O-glycosidation afforded stereospecifically the corresponding 1′-methyl-α-O-glycosides whose configurations were tentatively assigned by the NMR spectra, COSY and the C–H coupling constant 3JH−2′,Me−1′. The O-glycosidation of the acetyl protected 1-methylenesugars showed that the acetyl group at the C-2-O position was not effective to control the stereochemistry of the product by neighboring group participation because of the formation of a tertiary oxycarbenium ion as a stable intermediate.

A facile synthesis of 1′-C-alkyl-α-disaccharides from 1-C-alkyl-hexopyranoses and methyl 1-C-methyl-hexopyranosides

Abstract Direct O-glycosidations using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-hexopyranoses as the glycosyl donors were carried out with a catalytic amount (0.2 equiv.) of trimethylsilyl trifluoromethanesulfonate (TMSOTf). The glycosidations proceeded α-stereoselectively and furnished the corresponding 1′-C-alkyl-α-disaccharides in 71–90% yields. The O-transglycosidations from the benzylated and acetylated methyl 1-C-methyl-α-hexopyranosides to the corresponding 1′-C-methyl-α-O-disaccharides were also examined, respectively. These transglycosidations took place on α-stereoselectivity and provided the 1′-C-methyl-α-O-disaccharides as the sole products, implying that no neighboring group participation occured in the reactions.

Stereoselective synthesis and structure elucidation of spiro-ketodisaccharides

Abstract Cycloglycosylation of 3,4,5,7-tetra-O-benzyl-α- d -hept-2-ulopyranoses (2a–c) was carried out stereoselectively under the catalysis of Lewis acid to afford two spiro-cyclodisaccharides 3a–c and 4a–c in good yields. The reaction provided the kinetic products 3a–c or the thermodynamic products 4a–c as the predominant products under different conditions, respectively. The unprotected disaccharides 5a–c and 6a–c and the acetylated derivatives 7a–c and 8a–c were prepared by catalytic hydrogenation and followed by acetylation. The structures of compounds 4a–c, 6a–c and 8a–c were confirmed to be α,β-anomeric configuration with chair–chair–chair form for the tri-cycles based on the X-ray crystallographic analysis of 6a–c. The α,α-anomeric configurations of compounds 3a–c, 5a–c and 7a–c were determined based on the measurements of the three bond coupling constants 3JC,H between the C-1 and the H-3 of 7a–c.

A facile and improved preparation of glycosylidene acetals of monosaccharides

Abstract Glycosidic spiro-orthoesters were prepared from sugar lactones, diols, trimethylsilyl methyl ether and a catalytic amount of trimethylsilyl triflate in high yield. A key feature of this procedure is that diols can be directly used for this reaction without silylation.

Synthesis of Ketosyl Spiro-isoxazolidine by 1,3-Dipolar Cycloaddition of 1-Methylenesugars with Nitrones Å|A New Access to C-Glycosyl Amino Acids

The 1,3-dipolar cycloaddition reactions of 1-methylenesugars (la-c) with nitrones (2 and 5) were carried out diastereoselectively under the catalysis of BF 3 .Et 2 O at low temperature and afforded the α-stereoselective spiro ketosyl isoxazolidines in good to excellent yields. The reductive isoxazolidine ring-opening of the spiro moiety with the treatment of zinc and acetic acid resulted in a new kind of C-glycosyl amino acid possessing a ketose form, providing an access to C-glycosyl amino acids. The structures of the synthesized compounds were confirmed by the spectroscopic analyses.

A highly stereoselective β-(1→4)-glycosidic bond formation by reductive cleavage of cyclic orthoesters

Abstract Sterically congested glycosides, glycosyl-β-(1→4)-glycosides, were stereoselectively synthesized by reduction of glycosidic spiro-orthoesters with LiAlH 4 AlCl 3 . This novel transformation is especially valuable when it is applied to the preparation of mannosyl-β-(1→4)-glycoside which must be one of the most difficult tasks in carbohydrate chemistry.

A Highly Efficient and Shortcut Synthesis of Cyclitol Derivatives via Spiro Sugar Ortho Esters

Abstract Preparation of cyclitol derivatives from sugar lactones via spiro sugar ortho esters is described. The key steps are the novel enol ether formation from sugar ortho esters with AlMe3 and the efficient intramolecular aldol cyclization of alkyl enol ethers with ZnCl2 in THF/H2O. Firstly, the spiro sugar ortho esters 3a–c were prepared from the benzyl protected sugar lactones 1a–c and 2,2-dimethylpropanediol (2). These ortho esters were efficiently converted into the enol ethers 5a–c by the treatment of AlMe3 in CH2Cl2. The initial step of this reaction was the pyran ring cleavage accompanied by the methyl anion insertion, and the second was the dioxane ring opening caused by the Lewis acidity of AlMe3. The resulting alkyl enol ethers were treated with DMSO/Ac2O, and the formed keto compounds were converted into the carbasugars 9a–c by the ZnCl2-catalyzed aldol cyclization in THF/H2O. The overall yields of 9a, 9b, and 9c based on the corresponding lactones 1a–c were 64, 64, and 54%, respectively.

Presence of phospholipid-neutral lipid complex structures in atherosclerotic lesions as detected by a novel monoclonal antibody.

A novel monoclonal antibody (ASH1a/256C) that recognizes atherosclerotic lesions in human and Watanabe heritable hyperlipidemic (WHHL) rabbit aortae is described. When 123I-labeled ASH1a/256C antibody is injected intravenously into WHHL rabbits, it associates specifically with fatty streaks on the aorta. The antigen recognized by the antibody is lipid, based on extraction with chloroform and methanol from WHHL rabbit tissues. The antigen, purified by high performance liquid chromatography, was shown to be phosphatidylcholine (PC), which contains unsaturated fatty acyl groups based on analyses utilizing1H and 13C nuclear magnetic resonance, Fourier transfer-infrared spectrum, and mass spectrometry. The antibody did not react with other classes of phospholipids or neutral lipids when tested using an enzyme-linked immunosorbent assay. When PC was mixed with either cholesterol, cholesteryl ester, or triacylglycerol, however, the reactivity of the antibody to PC increased up to 8-fold. Homogenates of aorta tissue obtained from normal and WHHL rabbits were fractionated using sucrose density gradient ultracentrifugation in which neutral lipid droplets, cellular membranes, and proteins are separated. The phospholipid content in cellular membrane fractions from WHHL rabbits was twice as high as that of normal rabbits, and there was an enormous difference in the antigenic activity in these fractions. The content of cholesterol in the cellular membrane fraction of WHHL rabbits was approximately 50 times higher than that of normal rabbits. Addition of neutral lipids to the cellular membrane fraction of normal rabbit markedly increased the antigenic activity. Atheromatous lesions in thickened WHHL rabbit aortic intima that were rich in lipid droplets were stained positively with ASH1a/256C immunohistochemically. These results strongly suggest that PC-neutral lipid complex domains are formed in atherosclerotic lesions.