Glycal Derivatives Research Articles

Electrochemical Ferrier Rearrangement of Glycals.

The Ferrier rearrangement (FR) is a well-documented reaction that relies on strong acids or oxidants to convert glycals into unsaturated glycosyl derivatives. In this work, we introduce an electrochemical variant of the FR, offering a broad substrate compatibility. Various nucleophiles and glycal derivatives afford 2,3-unsaturated glycosyl derivatives in high yields with excellent diastereoselectivities. This sustainable method promises to expand the electrochemistry applications in sugar chemistry.

Operationally simple enzymatic deprotection of C-3 position on 3,4,6-tri-O-acetyl-d-glucal

The new strategies to obtain selectively protected hydroxyl function on sugar derivatives are still of the high value for the progress of glycochemistry and organic synthesis. Herein, we describe an interesting enzymatic deprotection strategy that was applied to the most commonly used glycal derivative – 3,4,6-tri-O-acetyl-d-glucal. The procedure is operationally simple, easy to scale-up and the biocatalyst might be effortlessly recycled from the reaction mixture. Resulting product – 4,6-di-O-acetyl-D-glucal we then challenged to synthesize two glycal synthons armed with 3 different protecting group – a synthetic target difficult to achieve with traditional methods.

Direct access to various C3-substituted sialyl glycal derivatives from 3-iodo-sialyl glycals.

A new and efficient method was developed for the synthesis of C3-substituted sialyl glycals that are useful for novel sialidase inhibitor discovery. This method was based on the cross-coupling reactions of 3-iodo-sialyl glycal methyl ester with boronic acids, alkenes and alkynes to directly introduce various functional groups to the sialyl glycal C3-position. A series of C3-aryl, alkyl, alkenyl, and alkynyl derivatives of sialyl glycal were efficiently and conveniently synthesized for the first time by this method, which has demonstrated its wide application scope.

Stereoselective Phenylselenoglycosylation of Glycals Bearing a Fused Carbonate Moiety toward the Synthesis of 2-Deoxy-β-galactosides and β-Mannosides.

A phenylselenoglycosylation reaction of glycal derivatives mediated by diphenyl diselenide and phenyliodine(III) bis(trifluoroacetate) under mild conditions is described. Stereoselective glycosylation has been achieved by installing fused carbonate on those glycals. 3,4-O-Carbonate galactals and 2,3-O-carbonate 2-hydroxyglucals are converted into corresponding glycosides in good yields with excellent β-selectivity, resulting in 2-phenylseleno-2-deoxy-β-galactosides and 2-phenylseleno-β-mannosides which are good precursors of 2-deoxy-β-galactosides and β-mannosides, respectively.

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates.

To synthesize nucleoside and oligosaccharide derivatives, we often use a glycosylation reaction to form a glycoside bond. Coupling reactions between a nucleobase and a sugar donor in the former case, and the reaction between an acceptor and a sugar donor of in the latter are carried out in the presence of an appropriate activator. As an activator of the glycosylation, a combination of a Lewis acid catalyst and a hypervalent iodine was developed for synthesizing 4’-thionucleosides, which could be applied for the synthesis of 4’-selenonucleosides as well. The extension of hypervalent iodine-mediated glycosylation allowed us to couple a nucleobase with cyclic allylsilanes and glycal derivatives to yield carbocyclic nucleosides and 2’,3’-unsaturated nucleosides, respectively. In addition, the combination of hypervalent iodine and Lewis acid could be used for the glycosylation of glycals and thioglycosides to produce disaccharides. In this paper, we review the use of hypervalent iodine-mediated glycosylation reactions for the synthesis of nucleosides and oligosaccharide derivatives.

Ferrier–Nicholas Cations from C‐3‐Alkynylglycals: Access to C‐3‐Branched Allylic Glycosides and Ring‐Opening Derivatives

Hexacarbonyldicobalt–C‐3‐alkynyl‐substituted glycal derivatives, when treated with BF3·OEt2 give rise to Nicholas‐stabilized Ferrier cation intermediates (Ferrier–Nicholas cations) that react with alcohols or C‐nucleophiles to give C‐3‐branched 2,3‐unsaturated glycosides or C‐glycosides, respectively. α‐C‐Glycosides were the sole compounds obtained when allyltrimethylsilane was used as the nucleophile. On the contrary, the reaction of C‐3‐alkynylglycals with heteroaryl or alcohol nucleophiles led to anomeric mixtures in which the β‐anomers prevailed. The presence of the hexacarbonyldicobalt–C‐3‐alkynyl substituent seems to be of key importance in the stereoselectivity of these transformations, since the reaction of C‐3‐alkynylglycals – devoid of the hexacarbonyldicobalt moiety – showed a preferred α‐stereoselectivity. Furthermore, a bis(indolyl) linear compound was obtained from the reaction of a hexacarbonyldicobalt–C‐3‐alkynylglycal with 2 equiv. of indole.

Diastereoselective Synthesis of Novel and Enantiopure Tetrahydropyrano[3,2-c]quinolines

Diastereoselective synthesis of novel and enantiopure N-alkylated tetrahydropyrano[3,2- c ]quinolines is described via intramolecular Friedel–Crafts alkylation using a 1- O -acetylglucosyl derivative as the key intermediate. Unprecedented formation of new glycal derivatives and α,β-unsaturated carbaldehyde products is also discussed.

ChemInform Abstract: Copper‐Mediated Direct Functionalization of Unsaturated C—C Bonds with Ethyl Bromo(difluoro)acetate: A Straightforward Access to Highly Valuable Difluoromethylated Alkenes.

ChemInformVolume 46, Issue 2 Preparative Organic Chemistry ChemInform Abstract: Copper-Mediated Direct Functionalization of Unsaturated C—C Bonds with Ethyl Bromo(difluoro)acetate: A Straightforward Access to Highly Valuable Difluoromethylated Alkenes. Marie-Charlotte Belhomme, Marie-Charlotte Belhomme INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorDelphine Dru, Delphine Dru INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorHeng-Ying Xiong, Heng-Ying Xiong INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorDominique Cahard, Dominique Cahard INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorTatiana Besset, Tatiana Besset INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorThomas Poisson, Thomas Poisson INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorXavier Pannecoucke, Xavier Pannecoucke INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this author Marie-Charlotte Belhomme, Marie-Charlotte Belhomme INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorDelphine Dru, Delphine Dru INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorHeng-Ying Xiong, Heng-Ying Xiong INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorDominique Cahard, Dominique Cahard INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorTatiana Besset, Tatiana Besset INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorThomas Poisson, Thomas Poisson INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this authorXavier Pannecoucke, Xavier Pannecoucke INSA Rouen, CNRS, Univ. Normandie, F-76821 Mont-Saint-Aignan, Fr.Search for more papers by this author First published: 19 December 2014 https://doi.org/10.1002/chin.201502045Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue2January, 2015 RelatedInformation

Epimerization of glycal derivatives by a cyclopentadienylruthenium catalyst: application to metalloenzymatic DYKAT.

Epimerization of a non-anomeric stereogenic center in carbohydrates is an important transformation in the synthesis of natural products. In this study an epimerization procedure of the allylic alcohols of glycals by cyclopentadienylruthenium catalyst 1 is presented. The epimerization of 4,6-O-benzylidene-D-glucal 4 in toluene is rapid, and an equlibrium with its D-allal epimer 5 is established within 5 min at room temperature. Exchange rates for allal and glucal formation were determined by 1D (1) H EXSY NMR experiments to be 0.055 s(-1) and 0.075 s(-1) , respectively. For 4-O-benzyl-L-rhamnal 8 the epimerization was less rapid and four days of epimerization was required to achieve equilibration of the epimers at room temperature. The epimerization methodology was subsequently combined with acylating enzymes in a dynamic kinetic asymmetric transformation (DYKAT), giving stereoselective acylation to the desired stereoisomers 12, 13, and 15. The net effect of this process is an inversion of a stereogenic center on the glycal, and yields ranging from 71 % to 83 % of the epimer were obtained.

Copper-Mediated Direct Functionalization of Unsaturated C–C Bonds with Ethyl Bromo(difluoro)acetate: A Straightforward Access to Highly Valuable Difluoromethylated Alkenes

A copper-mediated fluorofunctionalization of alkenes and alkynes has been developed. This method provides ready access to trisubstituted difluoromethylated olefins (from dihydropyrans, glycal derivatives, or terminal alkynes) or to tetrasubstituted olefins (from disubstituted alkynes). The products were obtained in good to high yields with acceptable E/Z selectivities. Finally, a first direct route to difluoromethylated alkynes is reported, albeit with low yields.

A convenient and efficient synthesis of glycals by zinc nanoparticles

A simple and efficient method for the synthesis of pyranoid glycals utilizing the reductive elimination of glycopyranosyl bromides by zinc nanoparticles in an acetate buffer is described. A variety of pyranoid glycal derivatives were obtained, especially for the synthesis of 6-deoxy-4,6-O-benzylidene and disaccharide glycals with good yields.

Palladium-Catalyzed Decarboxylative Allylation of Glycal Derivatives

Key words palladium - decarboxylative allylation - glycols - aspergillide A

ChemInform Abstract: Microwave‐Assisted Regioselective Benzylation: An Access to Glycal Derivatives with a Free Hydroxyl Group at C4.

AbstractD‐Glucal, D‐galactal (I), and their 6‐O‐protected derivatives, e.g. (IV), are benzylated in a two‐step sequence.

Nitrosyl Tetrafluoroborate Catalyzed Preparation of 2,3-Unsaturated Glycosides and 2-Deoxyglycosides of Hindered Alcohols, Thiols, and Sulfonamides

Nitrosyl tetrafluoroborate (NOBF₄) has been successfully applied as an efficient organocatalyst for the preparation of 2,3-unsaturated and 2-deoxyglycosides of hindered alcohols, aryl thiols, and aryl sulfonamides from glycal derivatives under the Ferrier rearrangement conditions. Product yields and stereo-outcomes were very good.

Stereoselective Synthesis of cis‐Fused Perhydrofuro[2,3‐b]furan Derivatives from Sugar‐Derived Allyl Vinyl Ethers

AbstractA stereoselective methodology has been developed for the construction of cis‐fused perhydrofuro[2,3‐b]furans, via 3‐C‐branched glycal derivatives, involving Claisen rearrangement of sugar‐derived allyl vinyl ethers, followed by a one‐pot ozonolysis and acid‐mediated acetalization. The methodology was used for the stereoselective synthesis of the P2 ligand in the recently FDA approved HIV protease inhibitor darunavir (Prezista). The methodology was also successfully used for the synthesis of cis‐fused perhydro‐5‐oxofuro[2,3‐b]furan derivatives.

Microwave-Assisted Regioselective Benzylation: An Access to Glycal Derivatives with a Free Hydroxyl Group at C4

D-glucal, D-galactal, and their 6-O-TBDMS derivatives were benzylated in a two-step procedure under microwave conditions. In the first step glycals were converted into dibutylstannylene acetal or tributyltin ether intermediates, which were next alkylated with benzyl bromide in the presence of Bu4NBr. In all cases the 4-OH group stayed unsubstituted. Microwave-assisted benzylation contributes to a significant reduction of the reaction time in comparison with the classical synthesis, which requires several hours of heating. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Carbohydrate Chemistry to view the free supplemental file.

Reaction of glycal derivatives with alcohols in the presence of N-bromosuccinimide and diphenyldiselenide: preparation of 2-deoxy-2-phenylselenyl glycosides

Reaction of glycal derivatives with alcohols or glycosyl acceptors in the presence of N-bromosuccinimide (NBS) and diphenyldiselenide resulted in the formation of alkyl 2-deoxy-2-phenylselenyl glycosides or disaccharide derivatives in excellent yield. The reactions are reasonably fast and considerable stereo-selectivity was observed in the preparation of disaccharide derivatives.

A New Route to N1-Substituted Uracil Derivatives Using Hypervalent Iodine

In continuation of our previous study, oxidative coupling reactions of uracil with allylsilane or enol ethers were examined using diacetoxyiodobenzene. The reaction of persilylated uracil with 3,4-dihydro-2<i>H</i>-pyran in the presence of TMSOTf and PhI(OAc)₂ resulted in the formation of a dihydropyranyluracil derivative, although the yield was low. In an extension of the oxidative coupling reaction, a novel glycosylation reaction using glycal derivatives as substrates was also developed. The treatment of persilylated uracil and 3,4-dihydro-2<i>H</i>-pyran with (PhSe)₂ and PhI(OAc)₂ in the presence of a catalytic amount of TMSOTf gave a 2,3-<i>anti</i>-derivative of 1-(3-phenylselanyltetrahydropyran-2-yl)uracil stereoselectively and in good yield.

Stereospecific novel glycosylation of hydroxy β-lactams via iodine-catalyzed reaction: a new method for optical resolution

Glycosylation of racemic and optically active α-hydroxy β-lactams by reaction with a few glycal derivatives in the presence of catalytic amounts of iodine has provided stereospecific formation of α-glycosides. This method has been extended for the preparation of optically active hydroxy β-lactams in excellent yields. The stereochemistry and nature of the glycals as well as the stereochemistry of the β-lactam ring has a profound influence for effective glycosylation.

Synthesis of 2-Deoxy-2-C-alkyl Glycal and Glycopyranosides from 2-Hydroxy Glycal Ester

A method to convert 2-hydroxy glycal ester to the corresponding 2-deoxy-2-C-alkyl glycal in a facile manner, through key reactions including (i) C-allylation at C-1, (ii) Wittig reaction, and (iii) Cope rearrangement of a 1,5-diene derivative, is reported. The α-anomer of the 1,5-diene derivative underwent Cope rearrangement to afford 2-deoxy-2-C-glycal derivative, whereas the β-anomer was found to be unreactive. Employing this sequence, 3,4,6-tri-O-benzyl-2-O-acetyl-1,5-anhydro-d-arabino-hex-1-enitol was transformed to 3,4,6-tri-O-benzyl-2-deoxy-2-C-alkyl-1,5-anhydro-D-arabino-hex-1-enitol. 2-Deoxy-2-C-alkyl glycal derivative is a suitable glycosyl donor to prepare 2-deoxy-2-C-alkyl glycosides, mediated through haloglycosylation and a subsequent dehalogenation. A number of 2-deoxy-2-C-alkyl glycosides, with both glycosyl and nonglycosyl moieties at the reducing end, are thus prepared from the glycal.