Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups

Dhakal, Bibek; Crich, David

doi:10.1021/jacs.8b09654

Cited by 44 publications

(60 citation statements)

References 116 publications

(193 reference statements)

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“… The Zbiral deamination of Pse thioglycoside 37 with a levulinic acid nucleophile, as reported by Dhakal and Crich, which enabled the expedient synthesis of diazido donor 42 . Nap: naphthyl, TIPS: triisopropylsilyl.…”

Section: Chemical Approaches To the Synthesis Of Pses And Glycosidesmentioning

confidence: 84%

“…Dhakal and Crich also developed a synthesis of Pse sugars by using 1 as a starting material . A Zbrial deamination by nitrosylation was similarly employed; on this occasion, a thioadamantyl (Ada) donor, 37 , was used as the substrate (Scheme ).…”

Section: Chemical Approaches To the Synthesis Of Pses And Glycosidesmentioning

confidence: 99%

“…However, the overall selectivity was seemingly still dependent on the acceptor, as demonstrated by glycosylation of serine acceptor 59 , which favoured α‐glycoside formation with both donors. Taking inspiration from Dhakal and Crich's use of an azido‐substituted Pse donor, the authors next screened modified N5‐azido SAda donor 60 , which lacked the potential participating Troc group, in an attempt to maximise β‐stereoselectivity (Scheme ). On this occasion NIS/TfOH activation in dichloromethane‐acetonitrile solvent mix afforded disaccharides 61 with complete stereoselectivity.…”

Section: Chemical Approaches To the Synthesis Of Pses And Glycosidesmentioning

confidence: 99%

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Synthetic Approaches for Accessing Pseudaminic Acid (Pse) Bacterial Glycans

et al. 2020

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Pseudaminic acids (Pses) are a group of non‐mammalian nonulosonic acids (nulOs) that have been shown to be an important virulence factor for a number of pathogenic bacteria, including emerging multidrug‐resistant ESKAPE pathogens. Despite their discovery over 30 years ago, relatively little is known about the biological significance of Pse glycans compared with their sialic acid analogues, primarily due to a lack of access to the synthetically challenging Pse architecture. Recently, however, the Pse backbone has been subjected to increasing synthetic exploration by carbohydrate (bio)chemists, and the total synthesis of complex Pse glycans achieved with inspiration from the biosynthesis and subsequent detailed study of chemical glycosylation by using Pse donors. Herein, context is provided for these efforts by summarising recent synthetic approaches pioneered for accessing Pse glycans, which are set to open up this underexplored area of glycoscience to the wider scientific community.

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Section: Chemical Approaches To the Synthesis Of Pses And Glycosidesmentioning

confidence: 84%

Section: Chemical Approaches To the Synthesis Of Pses And Glycosidesmentioning

confidence: 99%

Section: Chemical Approaches To the Synthesis Of Pses And Glycosidesmentioning

confidence: 99%

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Synthetic Approaches for Accessing Pseudaminic Acid (Pse) Bacterial Glycans

et al. 2020

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“…Carbohydrate chemistry is essential for accessing complex glycans that are used as tool compounds to investigate fundamental biological processes such as protein glycosylation 27 – 29 , as well as for the preparation of synthetic vaccines 30 – 32 . Predicting the outcome of carbohydrate transformations, such as regioselective protection/deprotection of multiple hydroxyl groups or the stereospecificity of glycosylation reactions, is a very difficult task even for experienced carbohydrate chemists 33 , 34 , implying that this field of research might particularly benefit from computer-assisted reaction prediction tools.…”

Section: Introductionmentioning

confidence: 99%

Transfer learning enables the molecular transformer to predict regio- and stereoselective reactions on carbohydrates

et al. 2020

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Organic synthesis methodology enables the synthesis of complex molecules and materials used in all fields of science and technology and represents a vast body of accumulated knowledge optimally suited for deep learning. While most organic reactions involve distinct functional groups and can readily be learned by deep learning models and chemists alike, regio- and stereoselective transformations are more challenging because their outcome also depends on functional group surroundings. Here, we challenge the Molecular Transformer model to predict reactions on carbohydrates where regio- and stereoselectivity are notoriously difficult to predict. We show that transfer learning of the general patent reaction model with a small set of carbohydrate reactions produces a specialized model returning predictions for carbohydrate reactions with remarkable accuracy. We validate these predictions experimentally with the synthesis of a lipid-linked oligosaccharide involving regioselective protections and stereoselective glycosylations. The transfer learning approach should be applicable to any reaction class of interest.

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“…According to precedents in the literature [53] anhydride appeared to be a logical deprotection step [26], the desired fluoro sugars were contaminated with varying quantities of unidentified by-products. However, clean debenzylation was achieved by first converting the azide to an acetamide on reaction with thioacetic acid [54][55]. Hence, the hemiacetals were reacted with thioacetic acid in pyridine to give acetamides 39-48 (Scheme 4) and the target trifluoro analogs 49 and 50.…”

Section: Scheme 3 Deoxyfluorination and O-benzylation Of Thioglycosimentioning

confidence: 99%

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide thiodonors

Hamala¹,

Šťastná²,

Kurfiřt³

et al. 2021

Preprint

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Multiple fluorination of glycostructures has emerged as an attractive way of modulating their protein affinity, metabolic stability, and lipophilicity. Here we described the synthesis of a series of mono-, di- and trifluorinated N-acetyl-D-glucosamine and D-galactosamine analogs. The key intermediates were the corresponding multiply fluorinated glucosazide and galactosazide thiodonors prepared from deoxyfluorinated 1,6-anhydro-2-azido-β-D-hexopyranose precursors by ring-opening reaction with phenyltrimethylsilyl sulfide. Nucleophilic deoxyfluorination at C4 and C6 by reaction with DAST, thioglycoside hydrolysis and azide/acetamide transformation completed the synthesis.

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Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups

Cited by 44 publications

References 116 publications

Synthetic Approaches for Accessing Pseudaminic Acid (Pse) Bacterial Glycans

Synthetic Approaches for Accessing Pseudaminic Acid (Pse) Bacterial Glycans

Transfer learning enables the molecular transformer to predict regio- and stereoselective reactions on carbohydrates

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide thiodonors

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