An Oxidation and Ring Contraction Approach to the Synthesis of (±)-1-Deoxynojirimycin and (±)-1-Deoxyaltronojirimycin

Bagal, Sharan K.; Davies, Stephen G.; Lee, James A.; Roberts, Paul M.; Russell, Angela J.; Scott, P M; Thomson, James E.

doi:10.1021/ol902533b

Cited by 50 publications

(19 citation statements)

References 21 publications

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“…Our groups and others have exploited the ring isomerization of seven-membered polyhydroxylated azacycles to generate new or known piperidine iminosugars. This transformation, based on a β-amino alcohol rearrangement, requires a free alcohol at the β-position and proceeds via a double S N 2 mechanism.…”

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confidence: 99%

Synthesis of 1,2-cis-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement

et al. 2014

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The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these α-D-GlcNAc and α-D-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring α-HGJ and α-HNJ. The α-D-GlcNAc-configured iminosugar was coupled to a glucoside acceptor to yield a novel pseudodisaccharide. Preliminary glycosidase inhibition evaluation indicates that the α-D-GalNAc-configured homoiminosugar is a potent and selective α-N-acetylgalactosaminidase inhibitor.

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confidence: 99%

Synthesis of 1,2-cis-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement

et al. 2014

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“…48 We first considered the epoxidation of the double bond in 12 followed by regioselectively ringopening by azide anion to introduce the amino substituent. Deceivingly, classical methodologies using m-chloroperoxybenzoic acid (MCPBA) or H 2 O 2 proved inefficient while harsher oxidant methods such as CF 3 CO 3 H 51,52 or oxone 49 generated inseparable 1:1 mixtures of the corresponding epoxides in moderate yields. We hypothesized that the rigid bicyclic skeleton of 12 was probably responsible for the low reactivity observed.…”

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confidence: 99%

Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors

et al. 2015

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2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of hexosaminidases and therefore show high therapeutic potential for the treatment of various diseases, including several lysosomal storage disorders. A stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc), the iminosugar analog of N-acetylglucosamine, with high overall yield is here described. This novel procedure further allowed accessing ureidoDNJNAc conjugates through derivatization of the endocyclic amine on a key pivotal intermediate. Remarkably, some of the ureido-DNJNAc representatives behaved as potent and selective inhibitors of β-hexosaminidases, including the human enzyme, being the first examples of neutral sp 2 -iminosugar-type inhibitors reported for these enzymes. Moreover, the amphiphilic character of the new ureido-DNJNAc is expected to confer better drug-like properties.

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“…This kinetically controlled ring opening was preceded via attack of the nucleophile at the site remote from the endocyclic oxygen atom where carbocationic character is better tolerated. 19,20 However, such a ring opening in a trans- bromonium ion is not favored energetically as it will involve a high energy twist boat like transition state. The relative stereochemistry of bromohydrin 16 was confirmed by NMR experiments.…”

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confidence: 99%

An improved asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol (D-142)

Gopishetty

Gogoi

Dutta

2011

Tetrahedron: Asymmetry

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Triple monoamine reuptake inhibitors have been implicated in the development of a new generation of antidepressants with higher efficacy than the currently existing therapies. In this paper, we have developed an alternative efficient synthetic route for triple monoamine reuptake inhibitor D-142 in 18.5% overall yield in 11 steps starting from diphenylmethane. D-142 was developed by us recently. The key step of the present synthetic strategy is the preferential formation of a bromohydrin from olefin via a cis-bromoinum intermediate, which introduced significant efficiency in the overall synthesis. Furthermore, we have developed an efficient way to recycle the optically active intermediate diol back to the desired chiral epoxide.

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An Oxidation and Ring Contraction Approach to the Synthesis of (±)-1-Deoxynojirimycin and (±)-1-Deoxyaltronojirimycin

Cited by 50 publications

References 21 publications

Synthesis of 1,2-cis-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement

Synthesis of 1,2-cis-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement

Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors

An improved asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol (D-142)

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