Robert M. Giuliano

Synthesis of methyl α-l-callipeltoside

Abstract The synthesis of callipeltose, a novel amino sugar with the proposed structure, 4-amino-4,6-dideoxy-2, O -3- C -dimethyl- l -talopyranosyl-3,4-urethane, from l -rhamnose is described. Oxime reduction, carbamate cyclization and selective methylation are key steps. The synthesis supports the assignment of the relative stereochemistry of callipeltose.

Synthesis of branched-chain sugars: a stereoselective route to sibirosamine, kansosamine, and vinelose from a common precursor

Methyl 4,6-dideoxy-3-C-methyl-4-(N-methyl-N-phenylsulfonylamino)-alpha-L- mannopyranoside and methyl 4-amino-4,6-dideoxy-3-C-methyl-alpha-L-mannopyranoside, derivatives of the branched-chain amino sugars sibirosamine and kansosamine, respectively, were synthesized by nucleophilic ring-opening of methyl 3,4-anhydro-6-deoxy-3-C-methyl-alpha-L-talopyranoside. Catalytic reduction of methyl 6-deoxy-2,3-O-isopropylidene-3-C-methyl-alpha-L-lyxo-hexopyrano sid-4-ulose gave the axial alcohol methyl 6-deoxy-2,3-O-isopropylidene-3-C-methyl-alpha-L-talopyranoside, a known precursor to vinelose.

SYNTHESIS OF VINYL α-D-GLUCOPYRANOSIDES FROM MIXED ACETAL GLYCOSIDES[1]

Vinyl D-glucopyranosides are useful intermediates in a wide variety of applications in synthetic carbohydrate chemistry. They have been utilized as chiral auxiliaries in the inverse-electron-demand cycloaddition with isoquinolinium salts, giving homochiral tetralins (Bradsher cycloaddition), and as precursors to enantiomerically pure cyclobutanols by [2 2] cycloaddition with ketenes. Vinyl glycosides that are unsaturated at C2-C3 undergo thermal Claisen rearrangement to give C-3 branched glycal derivatives. Isopropenyl and butenyl glycosides have been used as glycosyl donors in oligosaccharide synthesis. Vinyl glycosides and mixed acetal glycosides have been studied as substrates for glycosidases. In more recent studies, vinylated sugars, in which the vinyl group is attached to nonanomeric hydroxyl groups, have been utilized in the synthesis of cyclooctanoic mimetics of carbohydrates, as precursors to C-glycosides, and as intermediates in the synthesis of -mannosides by intramolecular tethering and delivery. Vinyl glycosides are most often synthesized from glucopyranosides with an unblocked anomeric hydroxyl group by transvinylation with mercuric acetate or from glycosyl halides by nucleophilic displacement with bis(acylmethyl)mercury reagents. Elimination reactions of 2-(phenylselenyl)ethyl glycosides and 2(trimethylammonium)-ethyl glycosides, and photolysis of 4-oxopentyl glycosides by Norrish Type II reactions also give vinyl glycosides. Our studies of hetero-Diels-Alder reactions in carbohydrate synthesis required access to vinyl D-glucopyranosides. A mercury-free preparation of vinyl ethers derived from chiral alcohols has been reported, in which treatment of mixed acetals with trimethylsilyl trifluoromethane sulfonate and an amine (Gassman method) gave good yields of vinyl ethers. We were intrigued by the possibility of synthesizing vinyl glycosides by the Gassman method, since the required monosaccharides that J. CARBOHYDRATE CHEMISTRY, 20(1), 81–85 (2001)

Synthesis of amicetose by three enantioselective methods

Abstract Three methods for the synthesis of the deoxy sugar amicetose (2,3,6-trideoxy- d - erythro -hexopyranoside) are described. All three utilize the known dihydropyran 2-isobutoxy-6-methyl-2,3-dihydro-4 H -pyran as an intermediate. Asymmetric hydroboration of the dihydropyran with IpcBH 2 gave enantiomerically enriched isobutyl α and β-amicetosides. Hydroboration with borane–tetrahydrofuran followed by derivatization of the major product (β-anomer) with R -(−)-1-(1-naphthyl)ethylisocyanate gave diastereomeric carbamates which were separated and converted to isobutyl β- d and β- l -amicetosides having high optical purity. Racemic isobutyl β-amicetosides were also resolved by enzymatic transesterification using lipase and an acyl transfer reagent. Porcine pancreatic lipase and lipases from Candida rugosa and Pseudomonas sp. were evaluated in the presence of either vinyl acetate, vinyl butyrate, or trifluoroethyl butyrate as acylating agents. A GC-based method for determining enantiomeric purity of amicetose derivatives was developed.

Synthesis of Glycosyl Azides by the Addition of Phenylselenenyl Azide to Glycals

Abstract The addition of phenylselenenyl azide to glycals is carried out under conditions that give 2-deoxy-2-phenylselenoglycosyl azides. This regiochemistry is opposite to that obtained under free-radical conditions, which are known to produce 2-azido-2-deoxyselenoglycosides. The addition reaction is carried out with phenylselenenyl chloride and sodium azide in dimethylformamide, and is stereoselective for trans addition. Tri-O-benzyl-d-glucal and di-O-benzyl-l-rhamnal each gave two addition products, in which the phenylselenyl and azido groups were either trans diaxial or trans diequatorial. Tri-O-benzyl-d-galactal gave only the trans diaxial addition product.

Structure of methyl 6-deoxy-α-d-idopyranoside

Abstract The conformation of the pyranoid ring of the l -idopyranosyluronic acid residues of heparin and dermatan sulfate is a matter of controversy. X-Ray crystallographic analysis of methyl 6-deoxy-α- d -idopyranoside ( 4 ), which has the same relative arrangement of substituents on the pyranose ring, shows that it adopts the 4 C 1 conformation having the four oxygen-containing substituents occupying axial positions and C-6 equatorial. The ring is slightly flattened, with torsion angles in the range of ±49.5 to 59.0(5)°. There are two intramolecular hydrogen bonds: O-2-H???O-4, 2.754(2) A, and O-3-H???O-1, 2.874(2) A, and the crystal structure is stabilized by an additional network of three intermolecular hydrogen-bonds. Analysis of the coupling constants obtained from the 1 H-n.m.r. spectrum of 4 suggests that, in solution, there is an equilibrium between the 4 C 1 form and another conformer, possibly a skew form. These results are discussed in relation to recent studies of the conformation of l -iduronic acid residues in heparin and dermatan sulfate.

Reductions of Methyl 2, 3-DI-O-Benzyl-4-Deoxyβ-L-Threo-Hex-4-Enodialdopyranoside

Abstract Selective reductions of the aldehyde and alkene functionalities in methyl 2, 3-di-O-benzyl-4-deoxy-β-L-threo-hex-4-enodialdopyranoside (4) are described. The title compound was synthesized in six steps from methyl α-D-glucopyranoside. Catalytic reduction of the C-4 - C-5 double bond in 4 gave either methyl 2, 3-di-O-benzyl-4-deoxy-α-D-xylo-hexodialdopyranoside (5) or methyl 2, 3-di-O-benzyl-4-deoxy-β-L-arabino-hexodialdopyranoside (10) in high stereoselectivity depending on the reaction conditions. The α-D-xylo product is a suitable precursor to higher-carbon sugars extended at the C-6 position. Reduction of both products with sodium borohydride gave the corresponding saturated alcohols 12 and 13. The aldehyde group in the title compound was reduced with diisobutylaluminum hydride to give allylic alcohol 11 which was hydrogenated to give, unexpectedly, alcohol 12 as the only product.

Addition Reactions of Benzenesulfinic Acid with Glycals and 1,2-Dibromosugars

The addition of benzenesulfinic acid to glycals was investigated under various conditions, and optimized yields of the glycosyl phenylsulfone products were obtained in the presence of tin tetrachloride as a catalyst. Double bond shift (Ferrier rearrangement) occurred in all cases except amicetal, which lacks a substituent at the allylic carbon. Glycosylation of benzenesulfinic acid with 1,2-dibromides was carried out using silver triflate as the promoter, and gave sulfinate esters as products by reaction at oxygen rather than at sulfur. The sulfinate esters were obtained as mixtures of stereoisomers at the stereogenic sulfur atom. Trapping of the sulfinates with carboxylate nucleophiles was observed during attempted oxidation with MCPBA.

An unusual course of thioglycoside activation with bromine: synthesis and crystal structure of 4-O-acetyl-2-bromo-2,3,6-trideoxy-3-C-methyl-3-trifluroacetamido-α-l-altropyranosyl bromide

Bromine activation of phenyl 4-O-acetyl-2,3,6-trideoxy-3-C-methyl-3-trifluoroacetamido-1-thio-alpha,beta-L-ribo-hexopyranoside and attempted coupling with an acceptor in the presence of silver silicate gave an unusual bicyclic product, 2-trifluoromethyl-(4-O-acetyl-2-bromo-2,3,6-trideoxy-3-C-methyl-alpha-L-altrohexopyrano)-[3,2,1-d,e]-2-oxazine, instead of the expected disaccharide. Detailed investigation supported by X-ray crystallographic analysis showed that a trans dibromide is an intermediate in this reaction and that the dibromide is likely formed from a glycal that is generated by elimination during the coupling step.

Synthesis of methyl α-l-vancosaminide

Abstract The synthesis of methyl α- l -vancosaminide from di- O -acetyl- l -rhamnal is described. The allylic alcohol methyl 2,3,6-trideoxy-3- C -methyl-α- l - threo -hex-2-enopyranoside was prepared from the glycal, 1,5-anhydro-1,2,6-trideoxy-3- C -methyl- l - ribo -hex-1-enitol, and converted to its N , N -dimethylisourea derivative. The cis amino alcohol functionality in vancosamine was introduced by the electrophilic cyclization of the isourea, followed by hydrolysis of the resulting oxazoline.