Glucopyranosyl Fluoride Research Articles

General and Stereocontrolled Approach to the Chemical Synthesis of Naturally Occurring Cyanogenic Glucosides.

An effective method for the chemical synthesis of cyanogenic glucosides has been developed as demonstrated by the synthesis of dhurrin, taxiphyllin, prunasin, sambunigrin, heterodendrin, and epiheterodendrin. O-Trimethylsilylated cyanohydrins were prepared and subjected directly to glucosylation using a fully acetylated glucopyranosyl fluoride donor with boron trifluoride-diethyl etherate as promoter to afford a chromatographically separable epimeric mixture of the corresponding acetylated cyanogenic glucosides. The isolated epimers were deprotected using a triflic acid/MeOH/ion-exchange resin system without any epimerization of the cyanohydrin function. The method is stereocontrolled and provides an efficient approach to chemical synthesis of other naturally occurring cyanogenic glucosides including those with a more complex aglycone structure.

Transition-state structure for the hydronium-ion-promoted hydrolysis of α-d-glucopyranosyl fluoride

The transition state for the hydronium-ion-promoted hydrolysis of α-d-glucopyranosyl fluoride in water has been characterized by combining multiple kinetic isotope effect measurements with theoretical modelling. The measured kinetic isotope effects for the C1-deuterium, C2-deuterium, C5-deuterium, anomeric carbon-13, and ring oxygen-18 are 1.219 ± 0.021, 1.099 ± 0.024, 0.976 ± 0.014, 1.014 ± 0.005, and 0.991 ± 0.013, respectively. The transition state for the hydronium ion reaction is late with respect to both C–F bond cleavage and proton transfer.

Direct thiophenylation accompanying orthoester-cleavage of 1,2,4-O-orthoacetyl-3,6-O-(o-xylylene)glucopyranose

The 3,6-O-(o-xylylene) bridge locks the conformation of glucopyranose to an axial-rich form. Although the conformational lock induces complete β-selectivity in a glycosylation reaction, the leaving group of the glycosyl donor is limited to fluorine. On the other hand, the bridge confers the furanose-preferred property to glucose, which makes synthesis of corresponding pyranosyl derivatives that equip various leaving groups difficult. This problem was solved through direct phenylthio glucosidation of 3,6-O-(o-xylylene)-1,2,4-O-orthoacetylglucose accompanying cleavage of the orthoester moiety. This paper describes the process of establishing direct thiophenylation. This process reduced the synthetic steps for the known glucopyranosyl fluoride and will expand application of conformationally locked glycosyl donors.

Synthesis of 3,6-O-(o-Xylylene)glucopyranosyl Fluoride, an Axial-Rich Glycosyl Donor of β-Glycosylation

Despite the reported complete β-selectivity in glycosylation with 2,4-di-O-benzyl-3,6-O-(o-xylylene)glucopyranosyl fluoride, its preparation has been inefficient. This paper describes an improved route for the donor, including the formation of the 3,6-bridge on 1,2,4-orthoacetylglucose, the preparation of which was also refined, along with a discovered feature that the 3,6-bridged glucose prefers the furanose form. Although this feature made the synthesis of the desired glucopyranosyl donor difficult, application of thermal glycosylation solved the problem. With a modifiable intermediate, the improved availability of the donor would expand the applications.

Completely β-Selective Glycosylation Using 3,6-O-(o-Xylylene)-Bridged Axial-Rich Glucosyl Fluoride

A completely β-selective glycosylation that does not rely on neighboring group participation is described. The novelty of this work is the design of the glycosyl donor locked into the axial-rich form by the o-xylylene bridge between the 3-O and 6-O of d-glucopyranose. The synthesized 2,4-di-O-benzyl-3,6-O-(o-xylyene)glucopyranosyl fluoride could efficiently react with various alcohols in a SnCl(2)-AgB(C(6)F(5))(4) catalytic system. The mechanism composed of the glycosylation and isomerization cycles was revealed through comparative experiments using acidic and basic molecular sieves. The achieved perfect stereocontrol is attributed to the synergy of the axial-rich conformation and convergent isomerization caused by HB(C(6)F(5))(4) generated in situ.

A Stepwise Solvent-Promoted SNi Reaction of α-d-Glucopyranosyl Fluoride: Mechanistic Implications for Retaining Glycosyltransferases

The solvolysis of α-d-glucopyranosyl fluoride in hexafluoro-2-propanol gives two products, 1,1,1,3,3,3-hexafluoropropan-2-yl α-d-glucopyranoside and 1,6-anhydro-β-D-glucopyranose. The ratio of these two products is essentially unchanged for reactions that are performed between 56 and 100 °C. The activation parameters for the solvolysis reaction are as follows: ΔH(++) = 81.4 ± 1.7 kJ mol(-1), and ΔS(++) = -90.3 ± 4.6 J mol(-1) K(-1). To characterize, by use of multiple kinetic isotope effect (KIE) measurements, the TS for the solvolysis reaction in hexafluoro-2-propanol, we synthesized a series of isotopically labeled α-d-glucopyranosyl fluorides. The measured KIEs for the C1 deuterium, C2 deuterium, C5 deuterium, anomeric carbon, ring oxygen, O6, and solvent deuterium are 1.185 ± 0.006, 1.080 ± 0.010, 0.987 ± 0.007, 1.008 ± 0.007, 0.997 ± 0.006, 1.003 ± 0.007, and 1.68 ± 0.07, respectively. The transition state for the solvolysis reaction was modeled computationally using the experimental KIE values as constraints. Taken together, the reported data are consistent with the retained solvolysis product being formed in an S(N)i (D(N)(++)*A(Nss)) reaction with a late transition state in which cleavage of the glycosidic bond is coupled to the transfer of a proton from a solvating hexafluoro-2-propanol molecule. In comparison, the inverted product, 1,6-anhydro-β-D-glucopyranose, is formed by intramolecular capture of a solvent-equilibrated glucopyranosylium ion, which results from dissociation of the solvent-separated ion pair formed in the rate-limiting ionization reaction (D(N)(++) + A(N)). The implications that this model reaction have for the mode of action of retaining glycosyltransferases are discussed.

A Novel Glycosidation of Glycosyl Fluoride Using a Designed Ionic Liquid and Its Effect on the Stereoselectivity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A novel glycosidation of glycosyl fluoride using a designed ionic liquid and its effect on the stereoselectivity

The glycosidations of glucopyranosyl fluoride and alcohols using an ionic liquid containing a protic acid effectively proceeded under mild conditions to afford the corresponding glycosides in good to high yields. The stereoselectivity of the glycosidation was significantly affected by the ionic liquid solvent. 1- n-Hexyl-3-methylimidazolium trifluoromethanesulfonate (C 6mim[OTf]), containing a trifluoromethanesulfonate anion, and 1-(3-cyanopropyl)-3-methylimidazolium trifluoromethanesulfonimidide (CNC 3mim[NTf 2]), possessing a cyano group at the side chain of the imidazolium cation, gave the β-stereoselectivity.

Highly α-Selective Glycosylation with Glycopyranosyl Fluorides Having Diethylthiocarbamoyl Group

Abstract Highly α-selective glycosylation of various glycosyl acceptors with glucopyranosyl fluoride having diethylthiocarbamoyl group at 6-position or galactopyranosyl fluoride having the same group at 4-position proceeded smoothly in the presence of a catalytic amount of protic acid to afford the corresponding disaccharides in high yields.

ChemInform Abstract: A Catalytic and Stereoselective Glycosylation with Glucopyranosyl Fluoride by Using Various Protic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Catalytic and Stereoselective Glycosylation with Glucopyranosyl Fluoride by Using Various Protic Acids

Abstract A catalytic and stereoselective glycosylation with glucosyl fluoride was effectively performed by using a catalytic amount of various protic acids. When the glycosylation was carried out, for example, using perchloric acid (HClO4) in diethyl ether (Et2O), the major products were α-glycosides while β-stereoselectivity was observed when tetrakis(pentafluorophenyl)boric acid [HB(C6F5)4] was used in a mixed solvent of trifluoromethylbenzene (BTF)–pivalonitrile (tBuCN) = (5:1). The stereoselectivity was controlled by not only the effect of solvent but also by the nature of counter anion of the catalyst such as B(C6F5)4− or ClO4−.

Glycosidation of solid-supported glycosyl donors tethered by a trialkylsilane linker

Glycosidation of silicon-connected glycosyl donors on polystyrene resin is described. Thiophenyl glycoside 2a and glucopyranosyl fluoride 2 b reacted with glycosyl acceptor 3 (R 2 = Bn) to give disaccharide 4a in 96% and 70% yields, respectively. Glycosidation of thiophenyl glucoside 2 a (R 1 = Bn or Bz) with glycosyl acceptor 3 (R 2 = Bn or Ac) yielded 4a–4c in satisfactory yields and 4d in moderate yield.

Synthesis of 6-deoxy-6,6-difluoro-α- d-glucopyranosyl fluoride

The synthesis of 6-deoxy-6,6-difluoro-α- d-glucopyranosyl fluoride from the benzyl-protected methylglucoside was accomplished in six steps.

Catalytic mechanism of glucoamylase probed by mutagenesis in conjunction with hydrolysis of alpha-D-glucopyranosyl fluoride and maltooligosaccharides.

The catalytic mechanism of glucoamylase (GA) is investigated by comparing kinetic results obtained using alpha-D-glucosyl fluoride (GF) and maltooligosaccharides as substrates for wild-type and four active site mutant GAs, Tyr116-->Ala, Trp120-->Phe, Asp176-->Asn, and Glu400-->Gln. These replacements decreased the activity (kcat/KM) toward maltose by 6-320-fold. Toward GF, however, Tyr116-->Ala and Trp120-->Phe GAs, showed wild-type and twice wild-type level activity, while Asp176-->Asn and Glu400-->Gln GAs had 22- and 665-fold lower activity, respectively. Glu400, the catalytic base, is suggested to strengthen ground-state binding in subsite 1, and Asp176 does so at subsites 1 and 2. Tyr116 and Trp120 belong to an aromatic cluster that is slightly removed from the catalytic site and not critical for GF hydrolysis, but which is probably involved in maltooligosaccharide transition-state stabilization. Since the mutation of groups near the catalytic site decreased activity for both GF and maltose, but substitution of Tyr116 and Trp120 decreased activity only for maltose, interaction with the substrate aglycon part may be implicated in the rate-limiting step. Rate-limiting aglycon product release was suggested previously for GA-catalyzed hydrolysis [Kitahata, S., Brewer, C. F., Genghof, D. S., Sawai, T., & Hehre, E. H. (1981) J. Biol. Chem. 256, 6017-6026]. For Glu400-->Gln and wild-type GA complexed with GF, the pH-activity (kcat) profile shows a pKa of 2.8. When these two enzymes were complexed with maltose, however, only wild-type GA had a titrating base group, assigned to Glu400 [Frandsen, T. P., Dupont, C., Lehmbeck, J., Stoffer, B., Sierks, M. R., Honzatko, R. B., & Svensson, B. (1994) Biochemistry 33, 13808-13816]. Thus, GF binding to Glu400-->Gln GA presumably elicits the deprotonation of a carboxyl group that facilitates catalysis.

ChemInform Abstract: Modification at C‐6 of Unprotected Glucopyranosyl Fluoride Using 6‐ Bromo‐6‐deoxy‐α‐D‐glucopyranosyl Fluoride as the Key Compound.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Carbohydrate Reactivity in Anhydrous Hydrogen Fluoride. Part 17. A Convenient Access to β‐(1 → 4)‐Linked 2‐Amino‐2‐deoxy‐D‐ glucopyranosyl Fluoride Oligosaccharides and β‐(1 → 4)‐ Linked 2‐Amino‐2‐deoxy‐D‐glucopyranosyl Oligosaccharides by Fluorolysis and Fluorohydrolysis of Chitosan.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Modification at c-6 of unprotected glucopyranosyl fluoride using 6-Bromo-6-deoxy-α-d-glucopyranosyl Fluoride as the key compound.

Abstract 6-Bromo-6-deoxy-α-d-glucopyranosyl fluoride (2) was prepared in good yield from α-d-glucopyranosyl fluoride (1) by treatment with PPh3 and CBr4 in pyridine. Catalytic reduction of 2 gave the corresponding 6-deoxy-α-d-glucopyranosyl fluoride (3) while treatment with NaN3 in DMF gave the 6-azido-6-deoxy-α-d-glucopyranosyl fluoride (4). The latter could be reduced to the 6-amino-6-deoxyglucosyl fluoride (5) which was converted into the 6-acetamido-6-deoxy-α-d-glucopyranosyl fluoride (6). The C-6 modified glucosyl fluorides 2, 3, 4, and 6 are crystalline compounds.

Regioselective Glycodesilylation of Silylated Glycosides as a Useful Tool for the Preparation of Oligosaccharides

Abstract A series of fully or partially protected alkyl and aryl 4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-d-glycopyranosides and 1-thio-β-d-glucopyranosides, respectively, were glycosylated by acetylated α-d-glucopyranosyl-, galactopyranosyl- and cellobiosyl fluoride under Lewis acid-catalysis to give the corresponding β-(1→6)-linked di- and trisaccharides, respectively, in moderate to high yield. With benzylated glucopyranosyl fluoride, anomeric mixtures of disaccharides were obtained depending on the solvent that was used for the glycosylation step. The initially formed oligosaccharides having a 1-fluoro-1,1,3,3-tetraisopropyl-1,3-disiloxane-3-yl substituent at position 4 were converted by treatment with tetrabutylammonium fluoride into the corresponding 4-OH compounds which are suitable as glycosyl acceptors for further extension of the sugar chain. Selective glycodesilylation of methyl 2-O-benzoyl-6-O-dimethylthexylsilyl-3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-α-d-glucopyr...

Polarimetry and 13C n.m.r. show that the hydrolyses of β-d-glucopyranosyl fluoride by β(1→3)-glucanases from Phanerochaete chrysosporium and Sporotrichum dimorphosporum have opposite stereochemistries

The time courses of optical rotation and fluoride ion release during hydrolysis of beta-D-glucopyranosyl fluoride by the beta(1-->3)-glucanase of Phanerochaete chrysosporium (J. L. Copa-Patiño and P. Broda, unpublished work) indicated that the initial sugar product was beta-D-glucopyranose. This was confirmed by monitoring the hydrolysis of 1-[13C]beta-D-glucopyranosyl fluoride by this enzyme with 13C n.m.r. (without proton decoupling). The same two techniques were used to confirm that hydrolysis of beta-D-glucopyranosyl fluoride by the exo beta(-->3)-glucanase of 'Basidiomycete QM 806' (identified as Sporotrichum dimorphosporum) yielded alpha-glucopyranose as first sugar product, in accordance with previous results using laminarin as substrate [Parrish and Reese (1963) Carbohydr. Res. 3, 424-429; Nelson (1970) J. Biol. Chem. 245, 869-872].

ChemInform Abstract: α‐Glucosylation Reactions with 2,3,4,6‐Tetra‐O‐benzyl‐β‐D‐ glucopyranosyl Fluoride and Triflic Anhydride as Promoter.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.