Showing papers on "Glycal published in 1998"

Convergent synthesis of n-linked glycopeptides on a solid support

Abstract: Solid-supported synthesis can be conducted to produce a variety of glycopeptides in good overall yields. The carbohydrates are formed by the glycal assembly method. The polymer-bound construct terminates in a glycal. The terminal double bond can be functionalized to provide a C2−N-acetyl glucosamine linkage with an amino group in the anomeric position. The latter can be coupled, in a convergent manner, to the γ-carboxyl group of an aspartyl residue on a preformed peptide. Iodosulfonamidation of the polymer-bound glucal to the N-acetyl glucosamine using anthracenesulfonamide was crucial for the success of the solid-phase synthesis. This general method was employed in the formation of a variety of glycopeptides.

Exploration of Modalities in Building α-O-Linked Systems through Glycal Assembly: A Total Synthesis of the Mucin-Related F1α Antigen

Abstract: The total synthesis of the F1α antigen, a member of the tumor-associated O-linked mucin glycopeptides, was achieved via two alternative routes. In the first approach, an α-O-linkage between serine/threonine and GalNAc (2-deoxy-2-N-acetylamino-d-galactose) was fashioned first. This prebuilt cassette was then linked to a lactosamine unit. Alternatively, assembly of the trisaccharide glycal preceded activation of the glycal double bond and the construction of the glycopeptide linkage. Both strategies lead to the desired glycosyl amino acid derivatives. During our investigation, we uncovered remarkable effects of even remote protecting groups on the reactivity and stereoselectivity of glycosidations.

Straightforward Synthesis of (1-->2)-Linked Pseudo Aza-C-disaccharides by the Novel Cycloaddition of Enantiopure Cyclic Nitrones to Glycals.

Abstract: The novel, highly stereoselective, intermolecular cycloaddition reaction of enantiopure cyclic nitrones 8 to 1,2-glycals 9 opens the way to a straightforward synthesis of a broad class of new (1→2)-linked pseudo aza-C-disaccharides 6, suitable substrates for selective inhibition of glycosidase enzymes. The cycloadditions occur with high stereocontrol, displaying preferential interaction between the bottom face of the glycal and the face of the nitrone anti to the substituent on C-3, with the reagents approaching in an exo fashion. The cycloadditions produced tricyclic isoxazolidines 7 that represent nonreducing pseudo aza-C-disaccharides stable to hydrolytic conditions. The target pseudo aza-disaccharides 6 were obtained by sequential deprotection of the hydroxyl groups and isoxazolidine ring-opening.

Solid Support Oligosaccharide Synthesis: Construction of β-Linked Oligosaccharides by Coupling of Glycal Derived Thioethyl Glycosyl Donors

Abstract: A solution to the problem of a solid-phase synthesis of β-(1→4) linked glucosides is described. The method involves conversion of polymer bound glycal to polymer bound thioethyl glucosyl donor bearing an α-oriented pivaloxy group at C2. The latter directs couplings with solution-based glycal acceptors in the β-sense. The ready-reiteratability of the method was demonstrated.

Straightforward synthesis of a derivative of purpurosamine C from d-galactose

Abstract: Purpurosamine C (1) is a component of the aminoglycoside antibiotic gentamicin C1a. A derivative of 1 was synthesized from d -galactose via its 2-acetoxy-3,4,6-tri-O-acetyl glycal (3). Compound 3 undergoes glycosylation with 2-propanol in the presence of SnCl4, with two succesive allylic rearrangements of the double bond to give isopropyl 6-O-acetyl-3,4-dideoxy-α- d -glycero-hex-3-enopyranosid-2-ulose (7). Compound 7 was hydrogenated, and O-deacetylated to afford 8. The free OH group of 8 was tosylated and substituted by azide, and the carbonyl function of the resulting ulose 10 reacted with hydroxylamine to give the E,Z-oximes (11,12). Highly diastereoselective reduction of the oxime acetate (13) by borane, which also reduced the azide function, led to the purpurosamine C derivative 14 (∼40% yield from 3).

Novel Heterocycloaddition Reaction of Glycals

Abstract: Diacyl thione species 1 has been generated and reacted in situ with both pyranoid and furanoid glycals to form novel [4 + 2] cycloadducts. Factors such as protecting groups and configuration of substituents in the glycals along with medium effects were varied to discover influences on face selectivity and reactivity. A qualitative correlation of reactivity with the HOMO−LUMO gap between the glycal (HOMO) and the heterodienic species (LUMO) is observed. In one example, the isolation of byproducts suggests that the cycloaddition may in fact be stepwise.

Exploration of Modalities in Building α-O-Linked Systems Through Glycal Assembly: A Total Synthesis of the Mucin-Related F1α Antigen.

Abstract: The total synthesis of the F1α antigen, a member of the tumor-associated O-linked mucin glycopeptides, was achieved via two alternative routes. In the first approach, an α-O-linkage between serine/threonine and GalNAc (2-deoxy-2-N-acetylamino-d-galactose) was fashioned first. This prebuilt cassette was then linked to a lactosamine unit. Alternatively, assembly of the trisaccharide glycal preceded activation of the glycal double bond and the construction of the glycopeptide linkage. Both strategies lead to the desired glycosyl amino acid derivatives. During our investigation, we uncovered remarkable effects of even remote protecting groups on the reactivity and stereoselectivity of glycosidations.

Facile Preparation of Protected Furanoid Glycals from Thymidine.

Abstract: The synthesis of O-silyl- and O-acyl-protected furanose glycals from free thymidine was investigated. The method of glycal formation reported by Pedersen et al. was successfully expanded to include 5-ester (toluoyl) protected glycals as well as various combinations of 5‘-ester and 3- and 5-tert-butyldimethylsilyl and tert-butyldiphenylsilyl protection. Gram quantities of furanoid glycals can be prepared in a few days in two−four synthetic steps in overall yields ranging from 17 to 80%.

Glycosylation of betulin acetates with glycals

Abstract: Betulin 2-deoxy-α-d-, 2-deoxy-α-l-, and 2,6-dideoxy-α-l-arabino-hexopyranosides were synthesized by acid-catalyzed glycosylation (cationite in the H+ form, LiBr) of betulin 3- and 28-monoacetates with glycal acetates.

Coupling of Glycal Derived Thioethyl Glycosyl Donors with Glycal Acceptors. An Advance in the Scope of the Glycal Assembly.

Abstract: Glycals were converted into thioethyl glycosyl donors through 1,2-anhydrosugar intermediates. Various participating groups in the C-2 position were examined for formation of β-glucosyl, β-galactosyl, and α-mannosyl linkages. A number of disaccharides was prepared employing a novel coupling protocol involving thioethyl 2-pivaloyl glycosyl donors and glycal acceptors. Using this methodology, a linear tetrasaccharide containing exclusively β-glucosyl-(1→4) linkages was prepared in high yields. Ready application to α-mannosylation and C2 branching are other hallmarks of the method.

Electrophilic Addition to 4‐Thio Furanoid Glycal: A Highly Stereoselective Entry to 2′‐Deoxy‐4′‐thio Pyrimidine Nucleosides.

Abstract: 4-Thio furanoid glycals with different types of O-silyl protection have been prepared from benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-d-erythro-pentofuranoside. Face-selectivity for PhSeCl- or N-iodosuccimide-initiated addition of a pyrimidine base to the thioglycal was found to be controlled by O-silyl protecting groups. Using the thioglycal protected with a 3,5-O-di-t-butylsilyl group, a highly stereoselective synthesis of β-2′-deoxy-4′-thio pyrimidine nucleosides has been accomplished.

Glycosylation of Betulin Acetates with Glycals.

Abstract: Betulin 2-deoxy-α-d-, 2-deoxy-α-l-, and 2,6-dideoxy-α-l-arabino-hexopyranosides were synthesized by acid-catalyzed glycosylation (cationite in the H+ form, LiBr) of betulin 3- and 28-monoacetates with glycal acetates.

Concise and Stereospecific Synthesis of Novel Bicyclic Dideoxynucleosides as Potential Antiviral Agents.

Abstract: A novel class of dideoxynucleosides containing a bicyclic sugar moiety, structurally related to the natural griseolic acids, was synthesized starting from the stereochemically defined compound, 1,4:3,6-dianhydro-D-glucitol. The key intermediate in the synthesis was a [3.3.0] fused bicyclic glycal. Glycosylation of this compound with nucleobase proceeded both regiospecifically and stereospecifically in the presence of an auxiliary agent, N-iodosuccinamide. Changes in stereochemistry during the synthesis was monitored by optical rotation data and confirmed by both 1D and 2D NMR experiments. The synthetic approach described possesses general usefulness.

Preparation of Modified Glycosyl Glycerol Derivatives by Glycal Rearrangement.

Abstract: By Lewis acid catalysed allylic rearrangement reactions of various glycals with glycerol derivatives 2,3-unsaturated mono- and disaccharide glycosyl glycerol derivatives were obtained in good yields. A triglycosyl glycerol was successfully synthesized in a straightforward three step way from 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol.