Efficient synthesis of 2,6,7,8-tetrahydroxyindolizidines (castanospermine analogues) via the dipolar cycloadditions of N-benzyl-C-(tetrofuranos-4-yl)nitrones to methyl acrylate
| Autor: | Pastora Borrachero, Manuel Gómez-Guillén, Sylvain Favre, Manuel Angulo-Álvarez, Francisca Cabrera-Escribano, Pierre Vogel, Ma Isabel Torres-Sánchez, Eleuterio Álvarez |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Indolizidines
Chemistry Stereochemistry Organic Chemistry Diastereomer Glycosidase inhibitors Indolizidine Dipolar cycloaddition Catalysis Cycloaddition Adduct Tetrahydroxyindolizidines Inorganic Chemistry chemistry.chemical_compound Synthesis Castanospermine Amine gas treating Physical and Theoretical Chemistry Methyl acrylate |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 19 páginas, 4 figuras, 2 tablas, 4 esquemas. The dipolar cycloaddition of (Z)-N-benzyl-(3-O-benzyl-1,2-O-isopropylidene-α-d-ribofuranos-5-ylidene)amine N-oxide to methyl acrylate gives a 53:16:26:5 diastereomeric mixture of isoxazolidine derivatives. The dipolar cycloaddition of the xylo analogue to methyl acrylate is more diastereoselective, producing a 44:13:43 mixture of only three diastereomers. The ribo-configured adducts have been converted (4 steps only) into the new (2R,6S,7S,8R,8aR)-, (2S,6S,7S,8R,8aR)-, (2S,6S,7S,8R,8aS)- and (2R,6S,7S,8R,8aS)-2,6,7,8-tetrahydroxyindolizidines. Similarly, the two xylo-configured major isoxazolidine derivatives were converted into the known derivatives (2R,6S,7R,8R,8aS)- and (2S,6S,7R,8R,8aR)-2,6,7,8-tetrahydroxyindolizidines. The six isomeric indolizidine derivatives obtained have been evaluated for their inhibiting activities towards 15 glycosidases. Only the (2R,6S,7S,8R,8aR)-configured isomer is a selective inhibitor of amyloglucosidases from Aspergillus niger (IC50 = 350 μM) and from Rhizopus mold (IC50 = 90 μM, Ki = 195 μM, non-competitive), the other indolizidines show very little inhibitory activity at 1 mM concentration. We thank the ‘Dirección General de Investigación, Ministerio de Ciencia y Tecnología’ of Spain (Grant No. BQU2000-1155), the ‘Dirección General de Universidades e Investigación, Consejería de Educación y Ciencia’ of Andalusia (FQM 142) and the Swiss Federal Science Foundation for financial support. We also thank Miss Catherine Schuetz for her technical assistance. |
| Databáze: | OpenAIRE |
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