Direct and Stereoselective Synthesis of β‐Linked 2,6‐Deoxyoligosaccharides

Tanaka, Hiroshi; Yoshizawa, Atsushi; Takahashi, Takashi

doi:10.1002/anie.200604031

Cited by 99 publications

(52 citation statements)

References 30 publications

(3 reference statements)

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“…The sulfonyl protecting group, initially explored as a strongly electron-withdrawing group at the 2-position capable of stabilizing manno- and rhamnopyranosyl triflates and other sulfonates, 71−73 and subsequently employed with varying degrees of success at the 4-position of 2,6-dideoxyglycopyranosyl donors, 74 and at the 3-, 4-, and 6-positions of other pyranosyl donors, 75,76 does not change the population of the side chain when replacing a benzyl ether at the 4-position of a glucosyl donor (Table 2, Figure 7b). The influence of the 4- O -sulfonyl group on glucopyranosylation can therefore be interpreted solely in terms of the change in electron-withdrawing ability.…”

Section: Discussionmentioning

confidence: 99%

Interplay of Protecting Groups and Side Chain Conformation in Glycopyranosides. Modulation of the Influence of Remote Substituents on Glycosylation?

2018

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The synthesis and conformational analysis of a series of phenyl 2,3,6-tri-O-benzyl-β-d-thio galacto- and glucopyranosides and their 6S-deuterio isotopomers, with systematic variation of the protecting group at the 4-position, are described. For the galactopyranosides, replacement of a 4-O-benzyl ether by a 4-O-alkanoyl or aroyl ester results in a small but measurable shift in side chain population away from the trans,gauche conformation and in favor of the gauche,trans conformer. In the glucopyranoside series on the other hand, replacement of a 4-O-benzyl ether by a 4-O-alkanoyl or aroyl ester results in a small but measurable increase in the population of the trans,gauche conformer at the expense of the gauche,gauche conformer. The possible modulating effect of these conformational changes on the well-known changes in the anomeric reactivity of glycosyl donors as a function of protecting group is discussed, raising the possibility that larger changes may be observed at the transition state for glycosylation. A comparable study with a series of ethyl 2,3,4-tri-O-benzyl-β-d-thioglucopyranosides reveals that no significant influence in side chain population is observed on changing the O6 protecting group.

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Section: Discussionmentioning

confidence: 99%

Interplay of Protecting Groups and Side Chain Conformation in Glycopyranosides. Modulation of the Influence of Remote Substituents on Glycosylation?

2018

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“…In discussing the increased β-selectivities observed in rhamnopyranosylation reactions with donor 5 , as compared to 6 , under homogeneous activation conditions, we agreed with van Boeckel and inclined toward the effect of the ester being one of an electron-withdrawing group influencing the tightness of the ion pairs on activation of the donor 9. In line with this hypothesis, Takahashi and coworkers observed excellent β-selectivity in a series of glycosylations conducted with a set of donors carrying electron-withdrawing but non-participating 4- O -sulfonate esters 22. Demchenko and coworkers, on the other hand, recently came down strongly on the side of neighboring group participation from O4 with donors 6 and 7 , even though the best β-selectivity recorded was only 7:1 21…”

Section: Introductionmentioning

confidence: 85%

Does Neighboring Group Participation by Non-Vicinal Esters Play a Role in Glycosylation Reactions? Effective Probes for the Detection of Bridging Intermediates

2008

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Neighboring group participation in glycopyranosylation reactions is probed for esters at the 3-Oaxial and equatorial, 4-O-axial and equatorial, and 6-O-sites of a range of donors through the use tert-butoxycarbonyl esters. The anticipated intermediate cyclic dioxanyl cation is interrupted for the axial 3-O-derivative leading to the formation of a 1,3-O-cyclic carbonate ester, with loss of a tertbutyl cation, providing convincing evidence of participation by esters at that position. However, no evidence was found for such a fragmentation of carbonate esters at the 3-O-equatorial, 4-O axial and equatorial and 6-O positions indicating that neighboring group participation from those sites does not occur under typical glycosylation conditions. Further probes employing a 4-O-(2-carboxy) benzoate ester and a 4-O-(4-methoxybenzoate) ester, the latter in conjunction with an 18 O quench designed to detect bridging intermediates, also failed to provide evidence for participation by 4-Oesters in galactopyranosylation.

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“…Other methods include the use of α-glycosyl phosphites,3 displacement of α-glycosylhalides,4 palladium catalyzed glycosylation reactions,5 utilization of alkoxy-substituted anomeric radicals, 6 and the use of glycosyl imidates as glycosyl donors under oxidative conditions. 7…”

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confidence: 99%

Stereoselective Synthesis of 2-Deoxy-β-glycosides Using Anomeric O-Alkylation/Arylation

Morris

Shair

2008

Org. Lett.

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Anomeric O-alkylation/arylation is applied to the synthesis of 2-deoxy-β-glycosides. Treatment of lactols with NaH in dioxane followed by the addition of electrophiles leads to the formation of 2-deoxy-β-glycosides in high yield and high selectivity. The high β-selectivity observed here demonstrates a powerful stereoelectronic effect for the stereoselective formation of acetals under kinetic control.2-Deoxy-β-glycosides are present in biologically active natural products such as the lomaiviticins, olivomycin A, OSW-1, and durhamycin. The stereoselective preparation of 2-deoxy-β-glycosides is difficult 1 because substituents at C2 often serve as directing groups during the glycosylation event. The synthesis challenge posed by 2-deoxy-β-glycosides coupled with their presence in nature has inspired a variety of approaches aimed at accessing these important glycosides. The most common methods involve the use of a heteroatom substituent at C2 of the glycosyl donor followed by its reductive removal after glycosylation. 2 Other methods include the use of α-glycosyl phosphites, 3 displacement of α-glycosylhalides, *E-mail: shair@chemistry.harvard.edu. Supporting Information Available: Experimental procedures and spectral data for all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org. We became interested in the synthesis of 2-deoxy-β-glycosides since they are present in the lomaiviticins, molecules we are targeting for synthesis (Figure 1). In particular, our recent synthesis of the central ring system of the lomaiviticins involves incorporation of the C4 and C4′ carbinols by S N 2 displacement of allylic sulfones with methoxide anions. 8 This raised the possiblity that the 2-deoxy-β-glycosides at C4 and C4′ might be incorporated via an anomeric O-alkylation using glycosyl-1-alkoxides. NIH Public AccessAnomeric O-alkylation with glycosyl-1-alkoxides generally affords high levels of β-glycosides. 9 An explanation for this selectivity involves rapid equilibrium between axial and equatorial alkoxides with the enhanced nucleophilicity of the equatorial alkoxide leading to selective generation of β-glycosides (Scheme 1). It has been proposed that the enhanced nucleophilicity of the equatorial alkoxide (II), compared to the axial alkoxide (I), is due to increased electron-electron repulsion resulting from the alkoxide of II being gauche to both electron lone pairs of the ring oxygen compared to a single gauche interaction in I. This phenomenon has been referred to as the kinetic anomeric effect, 9 or the β-effect, and may be similar to the α-effect, which is observed in molecules where the nucleophilic atom is directly attached to another heteroatom. To date, most examples of anomeric O-alkylation have been performed with substituents in the C2 position. 10 This has made it difficult to assess the contribution of the β-effect versus steric (or electronic) influences of C2 substitutents in the selective formation of β-glycosides by anomeric O-alkylation. In this paper we r...

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Direct and Stereoselective Synthesis of β‐Linked 2,6‐Deoxyoligosaccharides

Cited by 99 publications

References 30 publications

Interplay of Protecting Groups and Side Chain Conformation in Glycopyranosides. Modulation of the Influence of Remote Substituents on Glycosylation?

Interplay of Protecting Groups and Side Chain Conformation in Glycopyranosides. Modulation of the Influence of Remote Substituents on Glycosylation?

Does Neighboring Group Participation by Non-Vicinal Esters Play a Role in Glycosylation Reactions? Effective Probes for the Detection of Bridging Intermediates

Stereoselective Synthesis of 2-Deoxy-β-glycosides Using Anomeric O-Alkylation/Arylation

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