Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Efficient atropodiastereoselective access to 5,5′-bis-1,2,3- triazoles: Studies on 1-glucosylated 5-halogeno 1,2,3-triazoles and their 5-substituted derivatives as glycogen phosphorylase inhibitors
Δημιουργός/Συγγραφέας:	Goyard D. Chajistamatiou A.S. Sotiropoulou A.I. [EL] Χρυσίνα, Ευαγγελία Δ.[EN] Chrysina, Evangelia D. Praly J.-P. Vidal S.
Εκδότης:	Wiley-VCH Verlag
Ημερομηνία:	2014
Γλώσσα:	Αγγλικά
ISSN:	0947-6539
DOI:	10.1002/chem.201304989
Άλλο:	PubMed ID: 24677199
Περίληψη:	Whereas copper-catalyzed azide-alkyne cycloaddition (CuAAC) between acetylated β-D-glucosyl azide and alkyl or phenyl acetylenes led to the corresponding 4-substituted 1-glucosyl-1,2,3-triazoles in good yields, use of similar conditions but with 2 equiv CuI or CuBr led to the 5-halogeno analogues (>71 %). In contrast, with 2 equiv CuCl and either propargyl acetate or phenyl acetylene, the major products (>56 %) displayed two 5,5′-linked triazole rings resulting from homocoupling of the 1-glucosyl-4-substituted 1,2,3-triazoles. The 4-phenyl substituted compounds (acetylated, O-unprotected) and the acetylated 4-acetoxymethyl derivative existed in solution as a single form (d.r.>95:5), as shown by NMR spectroscopic analysis. The two 4-phenyl substituted structures were unambiguously identified for the first time by X-ray diffraction analysis, as atropisomers with aR stereochemistry. This represents one of the first efficient and highly atropodiastereoselective approaches to glucose-based bis-triazoles as single atropisomers. The products were purified by standard silica gel chromatography. Through Sonogashira or Suzuki cross-couplings, the 1-glucosyl-5-halogeno-1,2,3-triazoles were efficiently converted into a library of 1,2,3-triazoles of the 1-glucosyl-5-substituted (alkynyl, aryl) type. Attempts to achieve Heck coupling to methyl acrylate failed, but a stable palladium-associated triazole was isolated and analyzed by 1H NMR and MS. O-Unprotected derivatives were tested as inhibitors of glycogen phosphorylase. The modest inhibition activities measured showed that 4,5-disubstituted 1-glucosyl-1,2,3-triazoles bind weakly to the enzyme. This suggests that such ligands do not fit the catalytic site or any other binding site of the enzyme. Halide decides: The use excess CuI-halide (X=Br, I) in azide-alkyne cycloadditions leads to predominant formation of 5-halogeno-1,2,3-triazoles (see scheme). In contrast, with CuCl, the major products exhibit two 5,5′-linked triazole rings and represent an efficient and highly atropodiastereoselective access to glucose-based 5,5′-bis-triazoles. Subsequent Pd-catalyzed Sonogashira and Suzuki couplings afforded 5-alkynylated and 5-phenyl derivatives in good yield. The products moderately inhibit glycogen phosphorylase.
Τίτλος πηγής δημοσίευσης:	Chemistry - A European Journal
Τόμος/Κεφάλαιο:	20
Τεύχος:	18
Σελίδες:	5423-5432
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Χημεία (Γενικά)[EN] Chemistry (General)
Λέξεις-Κλειδιά:	atropisomerism carbohydrates click chemistry cross-coupling cycloaddition
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Σημειώσεις:	Seventh Framework Programme, FP7: 245866
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο