A General Approach to the Synthesis of 1-Deoxy-<scp>l</scp>-iminosugars

Guaragna, Annalisa; D’Errico, Stefano; D’Alonzo, Daniele; Pedatella, Silvana; Palumbo, Giovanni

doi:10.1021/ol7014847

Cited by 42 publications

(25 citation statements)

References 16 publications

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“…For the synthesis of racemic 1‐deoxymannojirimycin 2 (Scheme ), ester (±)‐ 15 was reduced to alcohol (±)‐ 19 (73 % after chromatography), which was protected as the SEM [2‐(trimethylsilyl)ethoxymethyl] ether (±)‐ 20 and finally subjected to hydroboration [BH 3 · THF in THF at –78 to 0 °C followed by oxidation with TMANO (trimethylamine N ‐oxide) in THF at reflux] to give diastereopure (±)‐ 21 in 60 % yield. Exhaustive hydrolysis quantitatively gave (±)‐ 2· HCl (11 % overall yield) as a white solid, the 1 H and 13 C NMR spectra of which were identical to those previously reported 16a,24…”

Section: Resultssupporting

confidence: 82%

Expeditious Racemic and Enantiodivergent Synthesis of 1‐Deoxymannojirimycin and 1,4‐Dideoxymannojirimycin

et al. 2012

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The racemic and enantiodivergent syntheses of 1‐deoxymannojirimycin (DMJ) and 1,4‐dideoxymannojirimycin have been realized through key enamide ester intermediates obtained by converting cis‐4,5‐dihydroxylated δ‐valerolactam derivatives into the corresponding enol phosphates and subjecting them to Pd‐catalyzed methoxycarbonylation. Further elaborations of these intermediates included stereocontrolled catalytic hydrogenation, for the synthesis of racemic 1,4‐dideoxymannojirimycin, and hydroboration/oxidation, for the synthesis of DMJ. Enantiodivergency was attained by optical resolution before exhaustive functional group deprotection, through the formation of diastereomeric camphanic esters. As the key racemic intermediate esters were easily prepared in a few steps on a large scale, and the final chromatographic separation of the camphanic esters was straightforward, this approach represents a convenient way to obtain both enantiomers of DMJ for medicinal chemistry studies.

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Section: Resultssupporting

confidence: 82%

Expeditious Racemic and Enantiodivergent Synthesis of 1‐Deoxymannojirimycin and 1,4‐Dideoxymannojirimycin

et al. 2012

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“…It has been recently reported that L ‐ allo ‐deoxynojirimycin ( 4 ; L ‐ allo ‐DNJ) is a moderate inhibitor of human lysosomal α‐mannosidase with an IC 50 value of 64 μ M 21. However, very few syntheses of this azasugar have been reported in the literature 9b,21,22. We realized that 19 could be an ideal precursor for the synthesis of this molecule.…”

Section: Resultsmentioning

confidence: 99%

Facile Aza‐Claisen Rearrangement of Glycals: Application in the Synthesis of 1‐Deoxy‐L‐iminosugars

Gupta

Vankar

2009

Eur J Org Chem

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“…Coupling reaction of this agent with the l-enantiomer of Garner aldehyde (94) led to alcohol 95, whose further elaboration allowed the obtainment of oxirane 96. Base-mediated epoxide ring opening of 96 followed by acidic hydrolysis of protecting groups gave stereoselectively access to the l-gluco configured iminosugar ent-2 [28,186]. l-NBDNJ (ent-4), the non-superimposable mirror image of NBDNJ, was obtained by standard N-alkylation reaction conditions of ent-2, while preparation of ent- (14,16,91,92) was performed by N-alkylation of l-DNJ with reactive alkyl and alkoxyalkyl iodides (98b and 100), in turn prepared by polymer supported triphenylphosphine (PSS-TPP)-mediated iodination reactions (Scheme 12) [187,188].…”

Section: Exploring the Role Of The Chirality In The Anti-inflamatory mentioning

confidence: 99%

Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis

Esposito

D’Alonzo

Fenza

et al. 2020

IJMS

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Iminosugars are sugar analogues endowed with a high pharmacological potential. The wide range of biological activities exhibited by these glycomimetics associated with their excellent drug profile make them attractive therapeutic candidates for several medical interventions. The ability of iminosugars to act as inhibitors or enhancers of carbohydrate-processing enzymes suggests their potential use as therapeutics for the treatment of cystic fibrosis (CF). Herein we review the most relevant advances in the field, paying attention to both the chemical synthesis of the iminosugars and their biological evaluations, resulting from in vitro and in vivo assays. Starting from the example of the marketed drug NBDNJ (N-butyl deoxynojirimycin), a variety of iminosugars have exhibited the capacity to rescue the trafficking of F508del-CFTR (deletion of F508 residue in the CF transmembrane conductance regulator), either alone or in combination with other correctors. Interesting results have also been obtained when iminosugars were considered as anti-inflammatory agents in CF lung disease. The data herein reported demonstrate that iminosugars hold considerable potential to be applied for both therapeutic purposes.

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A General Approach to the Synthesis of 1-Deoxy-l-iminosugars

Cited by 42 publications

References 16 publications

Expeditious Racemic and Enantiodivergent Synthesis of 1‐Deoxymannojirimycin and 1,4‐Dideoxymannojirimycin

Expeditious Racemic and Enantiodivergent Synthesis of 1‐Deoxymannojirimycin and 1,4‐Dideoxymannojirimycin

Facile Aza‐Claisen Rearrangement of Glycals: Application in the Synthesis of 1‐Deoxy‐L‐iminosugars

Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis

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