First Detection of Unprotected 1,2-Anhydro Aldopyranoses

Serizawa, Kazunari; Noguchi, Masato; Li, Gefei; Shoda, Shin Ichiro

doi:10.1246/cl.170348

Cited by 16 publications

(11 citation statements)

References 27 publications

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“…This data includes the wellknown differences in the rate of alkaline hydrolysis of 1,2-cis-versus 1,2-trans-glycosides, the reduced rate of alkaline hydrolysis of otherwise identical 2-alkylated 1,2-transglycosides 2 , and retention of anomeric stereochemistry in the alkaline methanolysis of 1,2trans-glycosyl fluorides whereas 2-alkylated 1,2-trans-glycosyl fluorides react with inversion 3 . Kinetic isotope effects for the alkaline hydrolysis of 4-nitrophenyl -Dmannopyranoside provided compelling evidence for neighboring-group participation by a C2-oxyanion 4 , and methods have recently been developed allowing for synthesis of 1,2anhydro sugars 5,6 . Over 40 years ago, Wallenfels proposed the biological equivalent of this reaction for LacZ -galactosidase involving nucleophilic participation by a pyranoside 2hydroxy group to form a 1,2-anhydro sugar (or 1,2-epoxide) intermediate 7 ; subsequently this enzyme was shown to utilize a standard retaining mechanism with an enzymatic nucleophile 8 .…”

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confidence: 99%

An Epoxide Intermediate in Glycosidase Catalysis

Sobala¹,

Speciale²,

Zhu³

et al. 2019

Preprint

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<div>Retaining glycoside hydrolases cleave their substrates through stereochemical retention at the anomeric position. Typically, this involves two-step mechanisms using either an enzymatic nucleophile via a covalent glycosyl enzyme intermediate, or neighboring group participation by a substrate-borne 2-acetamido neighboring group via an oxazoline intermediate; no enzymatic mechanism with participation of the sugar 2-hydroxyl has been reported. Here, we detail structural, computational and kinetic evidence for neighboring group participation by a mannose 2-hydroxyl in glycoside hydrolase family 99 endo-α-1,2-mannanases. We present a series of crystallographic snapshots of key species along the reaction coordinate: a Michaelis complex with a tetrasaccharide substrate; complexes with intermediate mimics, β-1,2-aziridine and β-1,2-epoxide; and a product complex. The 1,2-epoxide intermediate mimic displayed hydrolytic and transfer reactivity analogous to that expected for the 1,2-anhydro sugar intermediate supporting its catalytic equivalence. Quantum mechanics/molecular mechanics modelling of the reaction coordinate predicted a reaction pathway through a 1,2-anhydro sugar via a transition state in an unprecedented flattened, envelope (<i>E</i><sub>3</sub>) conformation. Kinetic isotope effects for anomeric-<sup>2</sup>H and anomeric-<sup>13</sup>C support an oxocarbenium ion-like transition state and that for C2-<sup>18</sup>O (1.052 ± 0.006) directly implicates nucleophilic participation by the C2-hydroxyl. Collectively, these data substantiate this unprecedented and long-imagined enzymatic mechanism.</div><div><br></div>

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confidence: 99%

An Epoxide Intermediate in Glycosidase Catalysis

Sobala¹,

Speciale²,

Zhu³

et al. 2019

Preprint

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“…1). [4] Proton NMR showed a doublet peak attributed to the anomeric proton at 5.10 ppm with a small coupling constant of 2.0 Hz. Compared with the 13 C NMR of α-aldopyranose [66] (C1 at 92.9 ppm, C2 at 72.5 ppm), a 15 ppm upfield shift was observed for the 1,2-anhydro aldopyranose (C1 at 78.7 ppm, C2 at 56.5 ppm), which clearly supports the existence of an oxirane ring, because the carbons in an oxirane ring are known to be detected at higher magnetic fields than those of other cyclic ethers due to the large ring distortion.…”

Section: First Detection Of Unprotected 12-anhydro Sugarsmentioning

confidence: 99%

“…Furthermore, in 2017, we firstly detected the unprotected 1,2-anhydro species by low-temperature NMR spectroscopy that allowed optimization of protection-free synthesis of glycosyl compounds. [4] In this review, an account is given of developments in 1,2-anhydro sugar chemistry, including synthetic methodologies of protected and unprotected 1,2-anhydro sugars, and their applications in the synthesis of oligosaccharides and glycoconjugates. glucal (99% yield, gluco-type only), and 3,4,6-tri-O-benzyl D-galactal (99% yield, galacto-type only) in a biphasic system.…”

Section: Introductionmentioning

confidence: 99%

Chemistry of 1,2-Anhydro Sugars

Noguchi

Serizawa

et al. 2018

Chimia

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The 1,2-anhydro sugars are a class of valuable and versatile intermediates in carbohydrate chemistry. In the first part of this article, a review is given on preparation methods of 1,2-anhydro sugars that are suitably protected. Protected 1,2-anhydro sugars have been widely used as glycosyl donors for the synthesis of glycosyl compounds such as oligosaccharides and nucleosides. In the second part, a brief history and the chemistry of unprotected 1,2-anhydro sugars is described. In the past few years, our research group has developed protection-free methods for synthesis of glycosyl compounds through unprotected 1,2-anhydro sugars as reactive intermediates based on the concept of 'direct anomeric activation'. In this article, the one-step preparation of glycosyl compounds such as thioglycoside derivatives and glycosyl azides by using formamidinium-type dehydrating agents is presented. Furthermore, the initial results on the first detection of unprotected 1,2-anhydro sugar intermediates by NMR measurements are shown along with their full structure characterizations.

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“… 15 DMC activation has been expanded to allow the direct synthesis of glycosyl thiols, 16 cyanomethyl thioglycosides, 17 glycosyl thiosulfates, 18 glycosyl dithiocarbamates, 19 and can even effect selective acetylation of the anomeric hydroxyl group of unprotected sugars in aqueous solution. 20 In these examples, high levels of 1,2- trans stereocontrol are generally observed, due to the intermediacy of either 1,2-anhydro sugars 21 or glycosyl oxazolines.…”

Section: Introductionmentioning

confidence: 99%