Enantiodivergent Formal Synthesis of (+)- and (−)-Cyclophellitol from <scp>d</scp>-Xylose Based on the Latent Symmetry Concept

Four series of C 7 N aminocyclitol analogues of glucose were synthesized by stereocontrolled epoxide opening of hydroxyl protected forms of the cyclohexane epoxides cyclophellitol and 1,6epi-cyclophellitol. The resulting hydroxymethyl substituted aminocyclitols were tested as glycosidase inhibitors. Cyclitols having an amino group in an α configuration at a position equivalent to the anomeric in the sugar were found to be low micromolar inhibitors of the α-glucosidase from baker's yeast with K i 's near to 2 μM. On the other hand, N-octyl aminocyclitols having the nitrogen substituents in an α or β configuration were found to be good inhibitors of recombinant β-glucocerebrosidase with K i values between 8.3 and 17 μM, and also inhibited lysosomal β-glucosidase activity in live cells at low-micromolar concentrations. A computational docking study suggests a differential binding among the different series of β-glucocerebrosidase inhibitors. In agreement with the experimental results, the binding poses obtained indicate that the presence of an alkyl lipid substituent in the inhibitor mimicking one of the lipid chains in the substrate is critical for potency. In contrast, the matching of hydroxymethyl substituents in the aminocyclitols and the parent glucosylceramide does not seem to be strictly necessary for potent inhibition, indicating the risk of simplifying structural analogies in sugar mimetic design.

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“…NMR data are consistent with those reported in the literature 21,32,33. ((1R,2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-7-oxabicyclo-[4 1…”

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confidence: 89%

Synthesis and Evaluation of Hydroxymethylaminocyclitols as Glycosidase Inhibitors

et al. 2015

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“…(221)) [1117,1118], hybrids of d-galactose with 1-deoxynojirimycin analogs [1119], the tetracyclic core of tetrapentalones [1120], 1-epi aglycon of cripowellins A and B [445], gambieric acid [1121], aspercyclide C [524], radicicol and pochonin C [1122], trachelanthamidine [1123], heliannuols G and H [652], (−)-Geismann-Waiss lactone [1124], tuberostemonines [688], (−)-kendomycin [1125], pochonin D [1126], (−)-223A [1127], coleophomones B-D [1128], brevetoxin B [130], garsubellin A [45], fostriecin [48], 11-acetoxy-4-deoxyasbestin D [1129], (+)-cyclophellitol [1130], ␤-C-glycosides [50], zoapatanol [247], deoxymannojirimycin and swainsonine [1131], valienamine [1132], A 3 adenosine recetor agonists [1133], vincantril [810], (−)-perhydrohistrionicotoxin [1134], annonaceous acetogenins [1135], deoxycombrestatin A-4 analogs [1136], (+)-lentiginosine and analogs [1137], N-malayamycin A [1138], (−)-salicylhalamides A and B [938], oxytocin analogs [1139], steroid-like compounds [440], (−)-isoprelaurefucin [338], halichondrin B [1140], (−)-microcarpalide and (+)-lethaloxin [1141,1142], anamarine …”

Section: Metathesis Reactionsmentioning

confidence: 99%

Transition metals in organic synthesis: Highlights for the year 2005

Söderberg

2008

Coordination Chemistry Reviews

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“…Diene 114 was then converted into cyclophellitol by metathesis, reduction, epoxidation and deprotection to give the natural product in a total of 9 steps and 14 % overall yield from D ‐xylose 59. Another cyclophellitol synthesis from xylose was also recently reported from the group of Kornienko, where the target molecule was assembled in 13 steps by the use of a Wittig methylenation and a 1,4‐addition of a vinylcopper reagent to install the two double bonds 60…”

Section: Application Of Ring‐closing Metathesis In Natural Productmentioning

confidence: 99%

Synthetic Strategies for Converting Carbohydrates into Carbocycles by the Use of Olefin Metathesis

Madsen

2007

Eur J Org Chem

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This microreview covers recent advances in the use of ring‐closing metathesis for the synthesis of carbocycles from carbohydrates. Various strategies for the synthesis of α,ω‐dienes from carbohydrates are presented, which give rise to a large variety of dienes with different stereochemistries, protecting groups and substituents. Subsequent ring‐closing metathesis with a ruthenium carbene complex affords highly functionalized carbocycles with ring sizes ranging from five‐ to eight‐membered rings. The application of these methods for the synthesis of carbocyclic natural products from carbohydrates is also demonstrated.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Enantiodivergent Formal Synthesis of (+)- and (−)-Cyclophellitol from d-Xylose Based on the Latent Symmetry Concept

Cited by 27 publications

References 29 publications

Synthesis and Evaluation of Hydroxymethylaminocyclitols as Glycosidase Inhibitors

Synthesis and Evaluation of Hydroxymethylaminocyclitols as Glycosidase Inhibitors

Transition metals in organic synthesis: Highlights for the year 2005

Synthetic Strategies for Converting Carbohydrates into Carbocycles by the Use of Olefin Metathesis

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