Showing papers on "Glycal published in 2004"

Rhenium(V)-Catalyzed Synthesis of 2-Deoxy-α-glycosides

Abstract: A mild method for the synthesis of 2-deoxysugars from the coupling of glycals with a range of nucleophiles is described. The method employs 1 mol % of an air- and moisture-tolerant rhenium−oxo complex [ReOCl3(SMe2)(Ph3PO)] as a catalyst for the formation of O-, N-, and S-α-glycosides. The catalytic system tolerates a number of commonly employed protecting groups, including isopropylidene acetals, alkyl and silyl ethers, acetates, and benzoates. Furthermore, the high-oxidation-state complex selectively catalyzes the coupling with the glycal acceptor in preference to oxidation of the glycals, alcohols, and even thiols.

Stereoselective palladium-catalyzed O-glycosylation using glycals

Abstract: A highly stereoselective palladium-catalyzed O-glycosylation reaction is described. The reaction of a glycal 3-acetate or carbonate with the zinc(II) alkoxide of acceptors establishes the glycosidic linkage under palladium catalysis to give rise to disaccharides as the product in good yields and with high stereoselectivity. In contrast to the Lewis acid mediated Ferrier procedure, the anomeric stereochemistry of this reaction is controlled by the employed ligand. Whereas the use of a complex of palladium acetate and 2-di(tert-butyl)phosphinobiphenyl as the catalyst results in the exclusive beta-glycoside formation, the same reaction using trimethyl phosphite ligand furnishes an alpha-anomer as the major product. The utility of the 2,3-unsaturation present in the resulting glycoside is demonstrated by the further transformations such as dihydroxylation, hydration, and hydrogenation reactions. Thus, the combination of the glycosylation and subsequent functionalization provides a novel entry to saccharides which are otherwise difficult to prepare. The broad scope of the process, mildness of the reaction conditions, and experimental simplicity should make this method a useful tool in synthetic carbohydrate chemistry.

Novel UDP-glycal derivatives as transition state analogue inhibitors of UDP-GlcNAc 2-epimerase.

Abstract: The "epimerisation" of UDP-GlcNAc to ManNAc, the first step in the biosynthesis of sialic acids, is catalyzed by UDP-GlcNAc 2-epimerase. In this paper we report the synthesis of transition state based inhibitors of this enzyme. To mimic the assumed first transition state of this reaction (TS 1), we designed and synthesized the novel UDP-exo-glycal derivatives 1-4. We also report herein the synthesis of 5 and 6, the first C-glycosidic derivatives of 2-acetamidoglucal, and the synthesis of the ketosides 7 and 8, which were designed as bis-substrate analogue and bis- product analogue, respectively, to mimic the second step of the reaction via the assumed second transition state TS 2.

Trimethylsilylnitrate−Trimethylsilyl Azide: A Novel Reagent System for the Synthesis of 2-Deoxyglycosyl Azides from Glycals. Application in the Synthesis of 2-Deoxy-β-N-glycopeptides

Abstract: A novel reagent system comprising Me 3 SiN 3 and 20 mol % of Me 3 SiONO 2 permits conversion of glycals to 1-azido 2-deoxy sugars in one step in fair to good yields. Galactals offer higher stereoselectivities than do the glucals. Reduction of the azide group with Ph 3 P-H 2 O to amino functionality followed by coupling with amino acids leads to the synthesis of novel 2-deoxy-β-N-glycopeptides irrespective of the geometry of initial azido sugars. Using this protocol, a new γ-sugar amino acid derivative is also procured.

Transformation of Glycals into 2,3‐Unsaturated Glycosyl Derivatives

Abstract: Various elimination procedures conducted on appropriate pyranoid and furanoid carbohydrate derivatives, especially on O-protected glycosyl halides afford cyclic vinyl ethers which Fischer (inappropriately) named glycals. These are used extensively in general organic synthesis and for the preparation of non-carbohydrate natural products as well as biologically important complex carbohydrates and glycoconjugates. The best known member, tri-O-acetyl-D-glucal, is normally made from tetra-O-acetyl-alpha-D-glucopyranosyl bromide, is commercially available, and is used very frequently in this chapter to represent the family in examples of the reactions under discussion. Because of the pronounced region- and stereoselectivities with which their addition reactions can be conducted, glycal derivatives are of major importance in synthesis. They also, however, take part in rearrangement processes that, likewise, have proved useful for synthesis. The principal one involves nucleophilic substitution of the allylic group with allylic rearrangement and results in products having double bonds in the 2, 3 positions and new substituents at the anomeric centers. By far the simplest and most commonly used way to this conversion involves the removal of the allylic substituent of the glycal and the generation of highly resonance-stabilized oxocarbenium ion intermediate. This may then react with nucleophiles at the anomeric center to give products as mixtures of diastereomers. Many examples and variations of this theme are described and form the major part of this chapter, but other ways are also considered Almost no formal mechanistic studies have been carried out on the reactions in this chapter. Categorization of mechanism required for the treatment of this topic has been done on the basis of conditions used, product identification and largely, chemical intuition. Keywords: glycals; transformation; oxocarbenium ions; regioselectivity; diasterioselectivity; nucleophilic substitutions; homoallylic center; addition-elimination reactions; palladium; leaving groups; electrocyclic reactions; unsaturated compounds; free sugars; glycosyl peroxides; glycosyl caroxylates; S-glycosides; glycosyl halides; glycosyl azides; glycosyl phosphonates; glycosyl hydrides; furanoid glycols; intramolecular applications; reverse reaction; reaction variations; scope; limitations; configuration; experimental procedures; other methods

Glycosylation with Sulfoxides and Sulfinates as Donors or Promoters

Abstract: The efficient, stereocontrolled formation of glycosidic bonds is arguably the most fundamental reaction in glycoscience. This chapter surveys four recent distinct glycosylation methods united by the common theme of employing sulfoxides, or closely related sulfinates, either in the glycosyl donor itself or as an integral part of the promoter. In the first method (the sulfoxide method), a glycosyl sulfoxide, the donor, is coupled to an acceptor alcohol by means of an activating agent to give the glycosidic bond. The activating agent is typically triflic anhydride, but other compounds have been used. In the second method (the thiogylcoside method) the donor is thioglycoside. It is activated by means of a promoter derived from the reaction of trifluoromethanesulfonic anhydride and thiosulfinate, a sulfinaminde, or diphenylsulfoxide before coupling to an acceptor alcohol. The third method is dehydrative coupling. This chapter is concerned only with the recent variations in which dehydration is achieved by means of a combination of diaryl sulfoxides and trifluoromethanesulfonic acid. The last method (the oxidative method), involves the direct oxidative glycosylation of glycals. This method differs significantly from the other methods since it does not employ a traditional anomeric derivative as glycosly donor, but derives one from the formal oxidation of glycal. At some time in the activation process, all four methods typically involve the reaction of a sulfoxide, or sulfinate with trifluoromethanesulfonic anhydride. All four methods possess the distinct advantage of using readily prepared, stable gylcosyl donors. Three of them are metal-free and two of them are capable of coupling to enable the most hindered unreactive alcohols in a matter of minutes at low temperature. These methods are some of the most powerful available for the formation of glycosidic linkages. Keywords: glycoslyation; mechanisms; oxidative method; sulfoxide method; dehydrative method; thioglycoside/sulfinate method; scope; limitations; donors; acceptors; N-Glycosides; nucleosides; C-Glycosides; sulfoxides; promoters; bond formation; synthesis applications; method comparisons; solvents; functional group compatibility; pyranoside; furnanosides; experimental procedures

Synergistic enhancement of catalytic activity of InCl3 - Me3SiCl combination towards carbon Ferrier rearrangement in glycal derivatives

Abstract: InCl3 (2 mol%) in combination with Me3SiCl (20 mol%) efficiently catalyze Ferrier rearrangement in a variety of glycal derivatives with different silyl nucleophiles to afford the corresponding Cpseudoglycals or unsaturated pyrans in nearly quantitative yields. The stereoselectivities of the C-glycosides are good to excellent in favor of the α-anomers. A stoichiometric amount of InCl3 is necessary for similar transformations in the absence of Me3SiCl. The InCl3 can be recovered and reused without any loss of its activity.

[4+2] and [2+2] Photocycloadditions of 1,2-diketones to glycal and hydroxyglycal esters ☆

Abstract: Photocycloadditions of phenanthrenequinone 1 and acenaphthenequinone 16 to 3,4,6-tri- O -acetyl- d -glucal proceeded with distinctly different regioselectivities: 1 preferentially adds with both carbonyl oxygens to give the [4+2] cycloadduct, a 1- O ,2- O -annelated α- d -glucoside (50% [ Chem. Ber. 1952 , 85 , 531]), while 16 reacts with only one carbonyl group to exclusively yield the [2+2] addition product, a 1- C ,2- O -oxetano-α- d -glucoside (86%). 2-Hydroxyglucal esters 11 and 12 also undergo photoadditions with 1 to give the cis -1,4-dioxane-fused cycloadducts 13 and 14 , whilst 16 fails to react. Structural and configurational assignments rest on NMR data and an X-ray analysis of spiro-pyranooxetane 18 .

Glycal-mediated syntheses of enantiomerically pure 3-azido-2,3-dideoxy-hexopyranosides and 3-amino-2,3-dideoxy-hexopyranolactones

Abstract: Methodology for the conversion of two commercially available glycals, d -galactal and d -glucal, into 3-azido-2,3-dideoxy-hexopyranosides and 3-amino-2,3-dideoxy-hexopyranolactones is reported. Using this strategy, templates suitable in combinatorial chemistry for the construction of a number of interesting biologically active molecules have been prepared. Key features of this strategy include the development of an efficient and original reaction sequence for the differential protection of the oxygen functionalities, the regio- and stereoselective introduction of the azido group, and the chemoselective oxidation of the acetal group.

A New Bismuth Nitrate-Induced Stereospecific Glycosylation of Alcohols.

Abstract: Bismuth nitrate-catalyzed stereospecific glycosylation of alcohol with glycal has been developed.

Synthesis of C-Aryl-Δ2,3-glycopyranosides via Uncatalyzed Addition of Triarylindium Reagents to Glycals.

Abstract: 2,3-Unsaturated- C -aryl glycopyranosides are important intermediates in the synthesis of medicinally important C -aryl glycosides. Treatment of glycal acetates with triarylindiums in ether at room temperature gives good yields of C -aryl-Δ 2,3 -glycosides of predominantly α-configuration. The mechanism of this reaction likely involves the formation of an oxocarbenium ion intermediate via indium(III) Lewis acid-assisted ionization of the glycal C.3 acetate. Coupling of trivinyl- and tris(alkynyl)indiums with glycals similarly led to C -vinyl- and C -alkynyl-Δ 2,3 -glycosides in good yield.

Stereoselective Palladium‐Catalyzed O‐Glycosylation Using Glycals.

Abstract: A highly stereoselective palladium-catalyzed O-glycosylation reaction is described. The reaction of a glycal 3-acetate or carbonate with the zinc(II) alkoxide of acceptors establishes the glycosidic linkage under palladium catalysis to give rise to disaccharides as the product in good yields and with high stereoselectivity. In contrast to the Lewis acid mediated Ferrier procedure, the anomeric stereochemistry of this reaction is controlled by the employed ligand. Whereas the use of a complex of palladium acetate and 2-di(tert-butyl)phosphinobiphenyl as the catalyst results in the exclusive beta-glycoside formation, the same reaction using trimethyl phosphite ligand furnishes an alpha-anomer as the major product. The utility of the 2,3-unsaturation present in the resulting glycoside is demonstrated by the further transformations such as dihydroxylation, hydration, and hydrogenation reactions. Thus, the combination of the glycosylation and subsequent functionalization provides a novel entry to saccharides which are otherwise difficult to prepare. The broad scope of the process, mildness of the reaction conditions, and experimental simplicity should make this method a useful tool in synthetic carbohydrate chemistry.

Chapter 12 The invention of the alkynol cycloisomerization reaction: Application to the synthesis of digitoxin

Abstract: Publisher Summary The first synthesis of carbohydrate-derived cyclic enol ethers (glycals) was developed by Emil Fischer early in the 20th century, featuring reductive elimination of glycosyl halides from carbohydrate starting materials. A newer approach to glycals features ring-closing metathesis of vinyl ethers with terminal alkenes. The development of methods for glycal synthesis has been accompanied by studies on the regio- and stereoselective functionalization of glycals, which can be applied to the introduction of functional groups at the 2-position. Thus, an endo-regioselective “alkynol cycloisomerization” process would provide another pathway to the synthesis of various cyclic enol ethers, including possibly glycals, if a reaction that is compatible with a variety of functional groups can be developed. With the discovery of six-membered ring formation via tungsten carbonyl reagents, the possibilities of synthesizing not only hexose sugars but also glycosides were considered. To test for the compatibility of alkynes with glycoside-forming methodologies, a microscale experiment with iodoglycosylation of chiral non-racemic alkynyl alcohol with commercially available tri-O-acetyl-D-glucal (25) has been conducted. The product iodoglycoside was observed as a single diastereomer by 1H-nuclear magnetic resonance (NMR) analysis of the reaction mixture.

Method for preparing enzymatic substrate analogs as inhibitors of bacterial heptosyl-transferases

Abstract: The invention relates to a A method for making osyl and hexoses derivatives of formula 1 , especially 2-fluoro-2-deoxy derivatives. wherein R is a nucleoside such as adenosine, cytidine, guanosine, uridine and deoxy analogs such as 2-deoxy, X represents OH, halogen, particularly F, NH 2 Y represents H, CH 2 OH, CH 2 NH 2 , CH 2 OPO 3 , CH 2 OSO 3 Z represents O or S, and W represents O, NH, or CH 2 , said method comprising the steps of: a) stereoselective fluorophosphorylation of tetrapivaleate 8 to give β-gluco-type fluorophosphate, b) hydrogenation and deprotection to give a monophosphate, c) coupling said glycal with (R)P-morpholidate to give crude sugar nucleotide 1 , or alternatively, d)deacetylation then silylation of heptaglycal 7 to give tetrasilylated glycal, e) fluorophosphorylation of said glycal to give β-gluco type fluorophosphate, f) deprotection of the fluorophosphate and coupling radical R to give 1 . Use of said derivatives as inhibitors of highly virulent proteins of pathogenic bacteria.

Synthetic studies on novel bryostatin analogues and their interaction with Crd2 of protein kinase C.

Abstract: A fully stereocontrolled asymmetric synthesis of the Southern Hemisphere intermediate 426 for the bryostatin family of antitumour agents is described in this thesis. It details how the strategy evolved from (E)-1,4-hexadiene 450 including a Roush-Masamune coupling between 462 and 507, cyclisation to glycal 505, selective epoxidation and in-situ Fischer glycosidation to 503 and an aldol / dehydration sequence to establish the (E)-exocyclic olefin. We also document a rare example of slow bond rotation in the C(18)- C(19)-bond of 426 and provide an explanation of this phenomenon. In addition, the synthesis of two truncated bryostatin analogs 525 and 526 is described, and the interaction of 525 with the CRD2 of human PKC-a discussed. [diagram].

Rhenium(V)-Catalyzed Synthesis of 2-Deoxy-α-glycosides.

Abstract: A mild method for the synthesis of 2-deoxysugars from the coupling of glycals with a range of nucleophiles is described. The method employs 1 mol % of an air- and moisture-tolerant rhenium−oxo complex [ReOCl3(SMe2)(Ph3PO)] as a catalyst for the formation of O-, N-, and S-α-glycosides. The catalytic system tolerates a number of commonly employed protecting groups, including isopropylidene acetals, alkyl and silyl ethers, acetates, and benzoates. Furthermore, the high-oxidation-state complex selectively catalyzes the coupling with the glycal acceptor in preference to oxidation of the glycals, alcohols, and even thiols.

Synthesis of C1-Alkyl- and Acylglycals from Glycals Using a B-Alkyl Suzuki—Miyaura Cross Coupling Approach.

Abstract: A B-alkyl Suzuki–Miyaura cross coupling approach provides a flexible, efficient means to convert glycals to C1-alkylglycals and C1-acylglycals that are versatile synthetic intermediates. This approach uses readily available glycal starting materials and overcomes major limitations associated with direct alkylation or acylation of glycals. Further, a commonly observed side reaction involving reduction of the halide coupling partner is suppressed by preincubation of the borane coupling partner with aqueous base, providing new mechanistic insights into the side reaction.

4‐Thiofuranoid Glycals: Versatile Synthons for Stereoselective Synthesis of 4′‐Thionucleosides

Abstract: 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.

Synthesis of the C‐Glycoside of Methyl α‐D‐Altropyranosyl‐(1→4)‐α‐D‐glucopyranoside.

Abstract: The C‐glycoside of methyl α‐d‐altropyranosyl‐(1→4)‐α‐d‐glucopyranoside 2 was prepared in a convergent fashion, from readily available precursors, 4‐O‐tert‐butyldiphenylsilyl‐1,2‐O‐isopropylidene‐d‐erythro‐S‐phenyl monothiohemiacetal 13 (five steps from D‐ribose) and the known acid, methyl 2,3,6‐tri‐O‐benzyl‐4‐C‐(carboxymethyl)‐4‐deoxy‐α‐d‐glucopyranoside 17 (seven steps from methyl α‐d‐glucopyranoside). The key reactions in the synthesis are the oxocarbenium ion cyclization of thioacetal‐enol ether 19 to a C1 substituted glycal 20, and the stereoselective hydroboration of 20 to the α‐C‐altroside 21. †This paper is Dedicated to Professor Gerard Decotes on the occasion of his 70th birthday.

From a glycal to a [1,3]dioxolan-4-yl ester

Abstract: 1,2:5,6-di-O-Isopropylidene-α- d -glucofuranose can be used as a starting material for the stereoselective synthesis of a novel [1,3]dioxolan-4-yl ester by an acid catalyzed rearrangement reaction of an unusual furanoid glycal.