161016-87-1

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• 2873-29-2 D-glucal triacetate 

Relevant academic research and scientific papers

β-Configured clickable [18F]FDGs as novel 18F-fluoroglycosylation tools for PET

In oncology and neurology the 18F-radiolabeled glucose analogue 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is by far the most commonly employed metabolic imaging agent for positron emission tomography (PET). Herein, we report a novel synthetic route to β-configured mannopyranoside precursors and a chemoselective 18F-fluoroglycosylation method that employ two β-configured [18F]FDG derivatives equipped with either a terminal azide or alkyne aglycon respectively, for use as a CuAAC clickable tool set for PET. The β-configured precursors provided the corresponding [18F]FDGs in a radiochemical yield of 77-88%. Further, the clickability of these [18F]FDGs was investigated by click coupling to the suitably functionalized Fmoc-protected amino acids, Fmoc-N-(propargyl)-glycine and Fmoc-3-azido-l-alanine, which provided the 18F-fluoroglycosylated amino acid conjugates in radiochemical yields of 75-83%. The 18F-fluoroglycosylated amino acids presented herein constitute a new and interesting class of metabolic PET radiotracers.

Soluble Polymer-Supported Ruthenium Porphyrin Catalysts for Epoxidation, Cyclopropanation, and Aziridination of Alkenes

(Matrix Presented) Attachment of poly(ethylene glycol) (PEG) to ruthenium porphyrin via a covalent etheric bond gives soluble polymer-supported ruthenium catalysts 3-5. These catalysts exhibit high reactivity and selectivity toward alkene epoxidation with 2,6-dichloropyridine N-oxide and alkene cyclopropanation with diazo compounds. The application of these catalysts in the synthesis of unstable organic compounds has been demonstrated.

Conformationally-locked N -glycosides: Exploiting long-range non-glycone interactions in the design of pharmacological chaperones for Gaucher disease

Pyranoid-type glycomimetics having a cis-1,2-fused glucopyranose-2-alkylsulfanyl-1,3-oxazoline (Glc-PSO) structure exhibit an unprecedented specificity as inhibitors of mammalian β-glucosidase. Notably, their inhibitory potency against human β-glucocerebrosidase (GCase) was found to be strongly dependent on the nature of aglycone-type moieties attached at the sulfur atom. In the particular case of υ-substituted hexadecyl chains, an amazing influence of the terminal group was observed. A comparative study on a series of Glc-PSO derivatives suggests that hydrogen bond acceptor functionalities, e.g. fluoro or methyloxycarbonyl, significantly stabilize the Glc-PSO:GCase complex. The S-(16-fluorohexadecyl)-PSO glycomimetic turned out to be a more potent GCase competitive inhibitor than ambroxol, a non glycomimetic drug currently in pilot trials as a pharmacological chaperone for Gaucher disease. Moreover, the inhibition constant increased by one order of magnitude when shifting from neutral (pH 7) to acidic (pH 5) media, a favorable characteristic for a chaperone candidate. Indeed, the fluoro-PSO derivative also proved superior to ambroxol in mutant GCase activity enhancement assays in N370S/N370S Gaucher fibroblasts. The results presented here represent a proof of concept of the potential of exploiting long-range non-glycone interactions for the optimization of glycosidase inhibitors with chaperone activity.

Conformationally-locked N -glycosides with selective β-glucosidase inhibitory activity: Identification of a new non-iminosugar-type pharmacological chaperone for gaucher disease

A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO(TFA)2 as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian β-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an S-(ω-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal β-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance.

Direct epoxidation of d-glucal and d-galactal derivatives with in situ generated DMDO

A multi-gram epoxidation of 3,4,6-tri-O-benzyl-d-glucal and d-galactal with dimethyldioxirane (DMDO) generated in situ from Oxone/acetone in a biphasic system (CH2Cl2-aqueous NaHCO3) resulted in the formation of

Ruthenium meso-tetrakis(2,6-dichlorophenyl)porphyrin complex immobilized in mesoporous MCM-41 as a heterogeneous catalyst for selective alkene epoxidations

A ruthenium complex of meso-tetrakis(2,6-dichlorophenyl)porphyrin, [RuII(TDCPP)(CO)(EtOH)], is immobilized into mesoporous MCM-41 molecular sieves; the supported Ru catalyst can effect highly selective heterogeneous alkene epoxidations using 2,6-dichloropyridine TV-oxide as terminal oxidant. Aromatic and aliphatic alkenes can be efficiently converted to their epoxides in good yields and selectivities, and cis-alkenes such as czs-stilbene, cis-β-methylstyrene, and cis-β-deuteriostyrene are epoxidized stereospecifically. Oxidation of cycloalkenes, e.g., norbornene and cyclooctene, can be carried out effectively using the heterogeneous Ru-catalyzed reaction while these alkenes are unreactive in the zeolite-based titanium silicate (TS-l)-catalyzed conditions (Murugavel, R.; Roesky, H. W. Angew. Chem., Int. Ed. Engl. 1997, 36, 477). On the other hand, the Ru/M-41(m) catalyst displays size selectivity in the (+)-limonene oxidation where the terminal C=C bond (vs internal trisubstituted C=C bond) becomes more readily oxidized. Bulky 3,4,6-tri-O-benzyl-D-glucal has failed to react under the heterogeneous Ru-catalyzed conditions, whereas the smaller acetyl derivative is converted to a 3:1 mixture of α- and β-glycal epoxides. The Ru/M-41(m) catalyst can be used repeatedly, and 67% of its initial activity is retained after 11 691 turnovers (three runs). The loss of activity is attributed to catalyst leaching and/or deactivation. On the basis of Hammett correlation (ρ+ = -0.72, R = 0.997) and product studies (cyclohexene and crs-alkenes as the substrates), a reactive dioxorutheniumCVI) porphyrin intermediate is not favored. An oxoruthenium(V) complex or oxoruthenium(IV) porphyrin cation radical could be the key intermediate for this highly selective epoxidation reaction.

A Stereoselective and Preparative Entry to 1,2-Anhydrosugars through Oxidation of Glycals with Perfluoro-cis-2,3-dialkyloxaziridines

Perfluoro-cis-2,3-dialkyloxaziridines 1 perform the direct epoxidation of glycals 2 to give cleanly corresponding 1,2-anhydrosugars 3 with medium to complete diastereoselection; elaboration of these glycals to glycosyl fluorides and lipid conjugates is al

A simple and highly diastereoselective preparation of glycal epoxides using the MCPBA-KF complex

Glycals are converted ro the corresponding epoxides in high yields by a diastereoselective one-step epoxidation using the m-chloroperoxybenzoic acid-KF complex in anhydrous dichloromethane.