Glycosidation Reactions Research Articles

Preparation of 1-Thio Uronic Acid Lactones and Their Use in Oligosaccharide Synthesis

The chemo- and regioselective TEMPO/BAIB-mediated oxidation of 2,6- and 3,6-dihydroxy 1-thio glycopyranosides to the corresponding 1-thio uronic acid lactones is described. These locked 1-thio glycuronides can directly be used as donors in glycosidation reactions using the Ph(2)SO/Tf(2)O reagent system. Alternatively, selective opening of the lactone bridge liberates a hydroxyl function for ensuing glycosylations.

A New Homobifunctional p‐Nitro Phenyl Ester Coupling Reagent for the Preparation of Neoglycoproteins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Dehydrative Glycosidation and Partially Benzylated Sugar Derivatives

AbstractFor Abstract see ChemInform Abstract in Full Text.

Solid-Phase Synthesis of Core 8O-Glycan-Linked MUC5AC Glycopeptide

The benzyl-protected disaccharide building blocks of core 8 O-glycan (15a/15b) for glycopeptide were stereoselectively synthesized by two glycosidation reactions with the glycosyl fluoride method. The building blocks were utilized in the solid-phase synthesis of a glycopeptide carrying two O-glycans with the consensus sequence of the tandem-repeat domain of MUC5AC. The synthetic glycopeptide was detached from the resin with reagent K, and subsequent debenzylation under conditions of low-acidity TfOH afforded glycopeptide 2. The synthetic sample will be used as a suitable standard in studies of the physicochemical or immunochemical characterization of mucin glycoforms.

Total Synthesis of Formamicin.

The enantioselective total synthesis of the cytotoxic plecomacrolide natural product formamicin (1) is described. Key aspects of this synthesis include the efficient transacetalation reactions of MOM ethers 28 and 38 to form the seven-membered formyl acetals 29 and 39, a late-stage Suzuki cross-coupling reaction of the highly functionalized vinyl boronic acid 6 and vinyl iodide 7, a highly beta-selective glycosidation reaction of beta-hydroxy ketone 4 with 2,6-dideoxy-2-iodoglucopyranosyl fluoride 3, and the global desilylation of penultimate intermediate 77 mediated by in situ generated Et(3)N.2HF.

Practical synthesis of 2'-deoxy-2'-fluoroarabinofuranosyl purine nucleosides by chemo-emzymatic method

Stereoselective introduction of a phosphate group into 2-fluorinated sugar (4) at the 1-position was developed by us for the first time. The resulting alpha-1-phosphate (1) was utilized to prepare 2'-deoxy-2'-fluoroarabinofuranosyl purine nucleosides (2), which were the key starting materials for the preparation of the 2'F-ANA-antisense molecule, by enzymatic glycosidation reaction. Next, we tried to apply this method as a practical synthesis of 2'F-araNs. Subsequently, we found an effect of additives on the direct phosphorylation of 1-bromide (4) with orthophosphoric acid. Tetra-n-butylammonium iodide was the most effective for achieving high alpha-selectivity among these additives. This reaction will be applicable for large-scale synthesis, and some 2'F-araNs were actually obtained in 30-40% yields from 1-O-benzoate (3). Thus, we proved the potency of the chemo-enzymatic synthesis of 2'F-ANs (2) by the use of alpha-1-phosphate (1).

Enzymatic glycosidation of sugar oxazolines having a carboxylate group catalyzed by chitinase

Enzymatic glycosidation using sugar oxazolines 1– 3 having a carboxylate group as glycosyl donors and compounds 4– 6 as glycosyl acceptors was performed by employing a chitinase from Bacillus sp. as catalyst. All the glycosidations proceeded with full control in stereochemistry at the anomeric carbon of the donor and regio-selectivity of the acceptor. The N, N′-diacetyl-6′- O-carboxymethylchitobiose oxazoline derivative 1 was effectively glycosidated, under catalysis by the enzyme, with methyl N, N′-diacetyl-β-chitobioside ( 4), pent-4-enyl N-acetyl-β- d-glucosaminide ( 5), and methyl N-acetyl-β- d-glucosaminide ( 6), affording in good yields the corresponding oligosaccharide derivatives having 6- O-carboxymethyl group at the nonreducing GlcNAc residue. The N, N′-diacetyl-6- O-carboxymethylchitobiose oxazoline derivative 2 was subjected to catalysis by the enzyme catalysis; however, no glycosidated products were produced through the reactions with 4, 5, and 6. Glycosidation reactions of the β- d-glucosyluronic-(1→4)- N-acetyl- d-glucosamine oxazoline derivative 3 proceeded with each of the glycosyl acceptors, giving rise to the corresponding oligosaccharide derivative having a GlcA residue at their nonreducing termini in good yields.

A New Homobifunctional p-Nitro Phenyl Ester Coupling Reagent for the Preparation of Neoglycoproteins

A new linker system has been designed and applied to neoglycoprotein synthesis. Reaction of oligosaccharide omega-aminoalkyl glycosides with homobifunctional adipic acid p-nitrophenyl diesters in dry DMF gave the corresponding amide half ester in good yields and of sufficient stability to permit chromatographic purification. Subsequent conjugation with bovine serum albumin under very mild conditions afforded the corresponding neoglycoproteins with good efficiency. The method is well suited for the coupling of very small amounts (mg) of oligosaccharide and protein. [structure: see text]

Dehydrative glycosidation and partially benzylated sugar derivatives

Dehydrative glycosidation reactions reported by the authors' group are reviewed. The authors' efforts were concentrated on developing reagent systems usable for one-stage-one-pot glycosidation. Such systems could simplify the glycosidation step using 1-OH sugar derivatives, since any preactivation stage for the hemiacetal OH group could be omitted. The systems, utilizing the dehydration potential of sulfonyl chloride, such as the p-nitrobenzenesulfonyl chloride-silver trifluoromethanesulfonate-triethylamine system as well as the p-nitrobenzenesulfonyl chloride-silver trifluoromethanesulfonate-N,N-dimethylacetamide-triethylamine system, were useful for the syntheses of many kinds of oligosaccharides. As a system free from any metals, the authors developed the trimethylsilyl trifluoromethanesulfonate-pyridine (TP) system. During the study of the system containing cobalt (II) bromide, the authors found that the bromide converts 1-OH sugar into the corresponding 1-Br derivative, which is then activated with the cobalt salt to undergo glycosidation with alcohol. To prepare partially benzylated sugar derivatives used as acceptors in the authors' studies, controlled benzylation and forced tritylation were carried out. Short syntheses of a variety of useful sugar derivatives using such convenient procedures are described. As a novel protecting group for the hemiacetal OH group, the authors used the 2-methoxyethyl group. Many kinds of trehalose-type disaccarides we prepared.

Glycosidation Reactions of Silyl Ethers with Conformationally Inverted Donors Derived from Glucuronic Acid: Stereoselective Synthesis of Glycosides and 2‐Deoxyglycosides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Total Synthesis of Formamicin

The enantioselective total synthesis of the cytotoxic plecomacrolide natural product formamicin (1) is described. Key aspects of this synthesis include the efficient transacetalation reactions of MOM ethers 28 and 38 to form the seven-membered formyl acetals 29 and 39, a late-stage Suzuki cross-coupling reaction of the highly functionalized vinyl boronic acid 6 and vinyl iodide 7, a highly beta-selective glycosidation reaction of beta-hydroxy ketone 4 with 2,6-dideoxy-2-iodoglucopyranosyl fluoride 3, and the global desilylation of penultimate intermediate 77 mediated by in situ generated Et(3)N.2HF.

Total synthesis of (-)-spinosyn A.

A convergent, highly stereoselective total synthesis of (-)-spinosyn A (1) is described. Key features of the synthesis include the transannular Diels-Alder reaction of macrocyclic pentaene 11 and the transannular Morita-Baylis-Hillman cyclization of 12 that generates tetracycle 26. The total synthesis of (-)-spinosyn A was completed by a sequence involving the highly beta-selective glycosidation reaction of 13 and glycosyl imidate 30.

Glycosidation Reactions of Silyl Ethers with Conformationally Inverted Donors Derived from Glucuronic Acid: Stereoselective Synthesis of Glycosides and 2‐Deoxyglycosides

Glycosidation Reactions of Silyl Ethers with Conformationally Inverted Donors Derived from Glucuronic Acid: Stereoselective Synthesis of Glycosides and 2‐Deoxyglycosides

Glycosidation reactions of silyl ethers with conformationally inverted donors derived from glucuronic acid: stereoselective synthesis of glycosides and 2-deoxyglycosides.

The donor makes the difference: The tin(IV) chloride catalyzed coupling of silyl ethers to donors derived from glucuronic acid has shown that the silyl ethers (see scheme) are significantly better acceptors than the corresponding alcohols or phenol. The reactions are highly stereoselective and dependant on the donor structure. They provide 1,2-trans- and 1,2-cis-(deoxy)glycosides in moderate to excellent yields.

Total synthesis of macroviracin D (BA-2836-4).

The first total synthesis of the complex glycolipid macroviracin D (BA-2836-4) (1) is described. This antivirally active metabolite isolated from the mycelium extracts of Streptomyces sp. BA-2836 incorporates a unique 46-membered macrodilactone motif decorated with glycosylated fatty acid appendices. Compound 1 consists of three identical subunits which are closely related to one of the segments found in cycloviracin B(1) (2), another antiviral glycoconjugate previously synthesized in our laboratory. Key steps of the synthesis route to 1 involve the stereoselective, ligand-controlled addition of the functionalized diorganozinc derivative 9 to aldehydes 8 a, b, a series of beta-selective glycosidation reactions using appropriately protected trichloroacetimidate donors, and three esterifications via the Yamaguchi method; one of them is performed intramolecularly to forge the macrocyclic lactone ring of the target in 89 % isolated yield. This total synthesis also firmly establishes the absolute configuration of the subunits of compound 1 as 3R,17S,23R.

Total Synthesis of Apoptolidin: Construction of Enantiomerically Pure Fragments.

A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed, and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is described. The projected total synthesis calls for a dithiane coupling reaction to construct the C20−C21 bond, a Stille coupling reaction to form the C11−C12 bond, and a Yamaguchi macrolactonization to assemble the macrolide ring, as well as two glycosidation reactions to fuse the carbohydrate units onto the molecule. First and second generation syntheses to the required fragments for apoptolidin (1) are described.

2,3-Anhydrosugars in glycoside bond synthesis. Application to the preparation of C-2 functionalized α- d-arabinofuranosides

A novel two-step route has been developed for the synthesis of a panel of oligosaccharides ( 9– 17 ) containing C-2 functionalized α- d-arabinofuranosyl residues. The first step in this route consists of a highly stereocontrolled glycosylation reaction using a 2,3-anhydrosugar thioglycoside ( 6 ). In the second step, the epoxide ring in the 2,3-anhydrosugar glycoside is regioselectively opened at C-2 with sodium methoxide and sodium azide thus providing products with the α- d-arabinofuranosyl stereochemistry. This approach to these targets circumvents the potential stereocontrol problems inherent in glycosylations with arabinofuranosyl donors possessing non-participating groups at C-2. The route is also highly convergent, allowing the preparation of a range of C-2′ and C-2″ modified oligosaccharides upon reaction of epoxy glycosides 27– 29 with nucleophiles.

2-Haloethyl 1-Thioglycosides as New Tools in Glycoside Syntheses. Part 1: Preparation, Characteristics, General Reactions

2-Haloethyl 1-thioglycosides are excellent leaving groups when the 2-haloethyl function is activated with silver salts or Lewis acids. These thioglycosides can be synthesized on the original Černý route or for better compatibility with the needs of a more complex glycoside synthesis, in stepwise procedures via 2-(2-tetrahydropyran-2-yloxy)ethyl glycosides or trityl 1-thioglycosides. The initial step in glycosidation reaction presumably proceeds via a thiiranium ion, which is responsible for their increased reactivity compared with normal thioethers as leaving groups in glycoside syntheses. Basic features of this new system with respect to reactivity and selectivity in disaccharide syntheses are described.

The C‐4 Configuration as a Probe for the Study of Glycosidation Reactions

AbstractThe difference in the electron‐withdrawing powers of axial and equatorial OBn was used as a probe to investigate the glycosidation reaction. The reactivity of perbenzylated glucosyl and galactosyl donors were compared under a range of glycosidation conditions that involved variations in catalyst, solvent, and glycosyl acceptor. Generally, the galactosyl donor had a reactivity four to five times higher than the glucosyl donor, which is in accord with the transition state having positive character. In certain cases, however, particularly when triflate was present, equal reactivity of glucosyl and galactosyl donors were found. The results are explained in terms of changes in the rate‐determining steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Total synthesis of apoptolidin: construction of enantiomerically pure fragments.

A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed, and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is described. The projected total synthesis calls for a dithiane coupling reaction to construct the C(20)-C(21) bond, a Stille coupling reaction to form the C(11)-C(12) bond, and a Yamaguchi macrolactonization to assemble the macrolide ring, as well as two glycosidation reactions to fuse the carbohydrate units onto the molecule. First and second generation syntheses to the required fragments for apoptolidin (1) are described.