Electrochemical bromochlorination of peracetylated glycals

Peracetylated glycals—3,4,5-tri-O-acetyl-d-glucal (1a), 3,4,5-tri-O-acetyl-d-galactal (1b) and 3,4-di-O-acetyl-6-deoxy-l-glucal (1c)—have been bromochlorinated by a suitable halogenating agent, generated electrochemically from a mixture of bromides and chlorides in dichloromethane. The reaction was performed in two ways: (i) by a constant current electrolysis (2 F mol⁻¹) of bromides and substrates in a milieu containing an excess of chlorides (Br^?/1/Cl^? = 1:1:6.8) and (ii) by anodic generation of free chlorine from chlorides (2 F mol⁻¹) and subsequent addition of bromides and substrates in a ratio Br^?/1 = 1:1. The corresponding 2-bromo-2-deoxy-glycopyranosyl chlorides were obtained in high yields.     

The iodosulfonamidation of peracetylated glycals revisited: access to 1,2-di-nitrogenated sugars

Iodosulfonamidation of peracetylated glycals was investigated using either a combination of N-iodosuccinimide/iodine or iodine chloride as a source of iodonium ion. 1,2-trans- and 1,2-cis-2-deoxy-2-iodo-1-sulfonamido hexoses were, respectively, obtained depending on the reagent system used. Both series of isomers were successfully converted to 1,2-di-nitrogenated compounds, for example, 1-azido-1,2-dideoxy-2-sulfonamido sugars, which are useful intermediates for the synthesis of N-linked glycoproteins or glycoconjugates.     

Fluorinated acyclo-C-nucleoside analogues from glycals in two steps

A convenient two-step strategy is reported for the synthesis of fluorinated optically pure acyclo-C-nucleoside analogues starting from simple glycals. In the first step, benzyl- or p-methoxybenzyl-protected glycals are treated with trifluoroacetic anhydride, bromodifluoroacetyl chloride, trichloroacetyl chloride, and perfluorooctanoyl chloride, respectively, in the presence of Et3N. This one-pot procedure yields 1,2-unsaturated sugars (1,5-anhydro-3,4,6-tri-O-benzyl (or p-methoxybenzyl) 2-deoxy-2-perhalogenoacyl-D-arabino / lyxo-hex-1-enitols 4-9) acylated at C-2. In the second step, a selective ring transformation is induced by treatment of the C-acylated glycals with bis-nucleophiles (hydrazine, phenylhydrazine, o-phenylenediamine, hydroxylamine). In particular, 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-trifluoroacetyl-D-arabino-hex-1-enitol (4) and 1,5-anhydro-2-deoxy-2-trifluoroacetyl-3,4,6-tri-O-(p-methoxybenzyl)-D-arabino-hex-1-enitol (8) were reacted with these nucleophiles generating the final C-nucleoside analogues of pyrazole (10, 11, and 12), diazepine (13), and isoxazole (15), respectively, containing a carbohydrate side chain linked to the heterocyclic ring.     

Reaction of acetyl hypofluorite with pyranoid and furanoid glycals

The regiospecific syn-addition of acetyl hypofluorite to glycals derived from pentopyranoses led to mixtures of stereoisomers. Stereospecific reactions occurred with furanoid glycals, the direction of addition being governed by the nature of the substituent at C-3. Whereas a benzyloxy group caused attack from the opposite, less-hindered face of the double bond, a hydroxyl group induced addition from the same side. From these reactions, 2-deoxy-2-fluoro derivatives of β-d-arabino-, α-d-ribo-, β-d-lyxo-, and α-d-xylo-pyranose as well as β-d-manno-, α-d-gluco-, α-d-ribo-, and β-d-arabino-furanose were obtainedl their ¹H-, ¹³C-, and ¹⁹F-n.m.r. data are given.     

Adducts of uridine and glycals as potential substrates for glycosyltransferases

We report on the synthesis of 2-deoxyglycosyl derivatives of uridine as potential donor substrates for glycosyltransferases. The totally stereoselective synthesis is accomplished by two sequential addition reactions of uridine derivatives to glycals promoted by triphenylphosphine-hydrogen bromide.     

Unexpected formation of glycals upon attempted C-alkylation of protected glycosylacetylenes

Treatment of 3,7-anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-D-glycero-D-galacto-oct-1 -ynitol (beta-D-mannosyl acetylene, 1) with 5 equivalents of n-butyllithium at either 0 or -78 degrees C resulted in the elimination of benzyl alcohol to yield 3,7-anhydro-5,6,8-tri-O-benzyl-1,2,4-trideoxy-D-arabino-oct-3-en-1-yn itol (glycal acetylene, 3) as the major product. Additional studies showed that 3 is also produced from two isomers of 1 with alpha-D-mannosyl and beta-D-glucosyl stereochemistry, but in lower yields. Furthermore, substrates in which the acetylene moiety is replaced by either a methyl or phenyl group do not produce a glycal product under these conditions. Finally, treatment of 1 with phenyllithium provides 3 in low yield. Deuterium labeling studies suggest that the reaction proceeds through an E2, rather than an E1cB, mechanism.     

A simple and convenient method for the synthesis of pyranoid glycals

A simple, mild, and environmentally benign synthesis procedure of pyranoid glycals is described. In a novel fashion, protected glycopyranosyl bromides undergo the reductive elimination in the presence of zinc in phosphate buffer at room temperature. The pyranoid glycals were obtained in good-to-excellent yields (18 examples).     

Epoxidation of C-branched glycals: unexpected stereochemical results and their theoretical rationale

This paper describes the synthesis of C-3 methyl-branched glycosides by epoxidation of partially unblocked L-configured glycals. The stereochemical result depends on the orientation of the allylic hydroxyl group. A theoretical explanation is presented, based on the conformational preferences of the respective glycal half-chair conformations that were estimated by applying the BP density functional and a valence triple-zeta basis set.     

4-Thiofuranoid glycals: versatile synthons for stereoselective synthesis of 4'-thionucleosides

Beta-anomers of 4'-thionucleosides have been synthesized stereoselectively, through PhSeCl- or N-iodosuccimide (NIS)-initiated electrophilic glycosidation to 3,5-O-(di-t-butylsilylene)-4-thiofuranoid glycal (1). This synthetic method has been applied to the synthesis of those analogues branched at the anomeric position using 1-C-carbon-substituted 3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-4-thiofuranoid glycals (11-14) prepared based on lithiation of 10.     

Addition to the Flea Fauna of Vietnam

Entomological Review - Analysis of the literature data has shown that the present day flea fauna of mammals in Vietnam is represented by 50 flea species. In 2019–2020, we surveyed seven...     

Semisynthetic epsilon-isorhodomycins: their synthesis using glycals and their structure-activity relationship

Syntheses and structure-activity relationships of 7-O-(3-amino-2,3,6-trideoxy-a-L-lyxo- (18), -L-arabino- (20) and -L-ribo- hexopyranosyl)-epsilon-isorhodomycins (25) and their 3'-dimethylamino derivatives 22, 23 and 26 are described. Condensation (trimethylsilyl triflate, molecular sieves 4 A, 10:1 dichloromethane-acetone, -15 degrees) of epsilon-isorhodomycinone (epsilon-isoRMN, 6) with 1,5-anhydro-4-O-p-nitrobenzoyl-3-trifluoroacetamido-L-lyxo- (5) -L-arabino- (9) or -L-ribo-hex-l-enitols (10) afforded mainly the 7-O-a-glycosyl-epsilon-isoRMNs 7, 11, and 12. Similar glycosylation of 6 with 1,5-anhydro-3-azido-4-O-p-nitrobenzoyl-2,3,6-trideoxy-L-arabino-hex-1-++ +enitol (15) yielded a-glycoside 16. Removal (M NaOH) of the p-nitrobenzoyl and trifluoroacetyl groups from 7, 11, and 12 gave the 7-O-(3-amino-2,3,6-trideoxy-a-L-hexopyranosyl)-epsilon-isoRMNs 18, 20, and 25. Reductive alkylation (CH2O, NaCNBH3) of these products afforded the 3'-N,N-dimethyl analogues 22, 23, and 26. The cytotoxic effect (IC50) of the semisynthetic epsilon-isorhodomycins was tested in vitro in leukemia cell line L1210.     

The formation of α,β-unsaturated aldehydes in the hydrolysis of acetylated glycals

The hydrolysis of d-glucal triacetate (1), d-galactal triacetate (11), and d-arabinal diacetate (6) in refluxing, aqueous 1,4-dioxane has been investigated; each of these compounds is readily converted into a partially acetylated aldehydo-hex-2-enopyranose via the related pseudo-glycal. The latter constitutes the major component after brief reaction, and the conversion of each into the unsaturated aldehyde is inhibited in the presence of hydroquinone. Generally, the process is promoted by the addition of some acetic acid. Acetyl migration occurs during the reaction, and isolation of the aldehyde is best effected by acetylating the crude product and fractionating it on dimethyl sulfoxide-impregnated paper. Of the three examples studied, the yield of aldehyde is highest for 1 and lowest for 11.     

Synthesis of 2-deoxy-2-fluorohexoses by fluorination of glycals in aqueous media

1,5-Anhydro-2-deoxy-d-arabino- (d-glucal), 1,5-anhydro-2-deoxy-d-lyxo- (d-galactal), and 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-lyxo-hex-1-enitol (3,4,6-tri-O-acetyl-d-galactal) (3) were fluorinated in water and organic solvent-water with molecular fluorine and, for ¹⁸F-labelled compounds, with [¹⁸F]fluorine. Chemical yields of 40 and 10% were obtained for 2-deoxy-2-fluoro-d-glucose and 2-deoxy-2-fluoro-d-mannose, respectively, and 35 and 5% for 2-deoxy-2-fluoro-d-galactose (12) and 2-deoxy-2-fluoro-d-talose (13), respectively. In the fluorination of 3, the chemical yields of 12 and 13 were 38 and 6%, respectively. An l.c. separation of 2-deoxy-2-fluoro-d-hexoses is described.     

Synthesis of furanose glycals from furanose 1,2-diols and their cyclic thiocarbonate esters

Two new methods for the synthesis of furanoid glycals are described. Both procedures were shown to be faster and cheaper that those previously reported. Protected 1,2-dihydroxypento- and hexo-furanose derivatives with the -xylo, -gluco and -ribo, -allo configurations were used as starting material to afford the corresponding C-3,4 -threo and -erythro glycals derivatives.