Synthesis and evaluation of sulfamide-type indolizidines as glycosidase inhibitors

被引：32

作者：

Benltifa, Mahmoud ^{[2
]}

Moreno, M. Isabel Garcia ^{[1
]}

Mellet, Carmen Ortiz ^{[1
]}

Fernandez, Jose M. Garcia ^{[3
]}

Wadouachi, Anne ^{[2
]}

机构：

[1] Univ Seville, Fac Quim, Dept Quim Organ, E-41071 Seville, Spain

[2] Univ Picardie, CNRS, Lab Glucides, UMR 6219, F-80039 Amiens, France

[3] Univ Seville, CSIC, Inst Invest Quim, E-41092 Seville, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 09期

关键词：

cyclic sulfamide; indolizidine; mannosidases inhibitor;

D O I：

10.1016/j.bmcl.2008.04.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A practical synthesis of reducing sulfamide-derived iminosugar glycomimetics related to the indolizidine glycosidase inhibitor family is reported. The polyhydroxylated bicyclic system was built from readily accessible hexofuranose derivatives through a synthetic scheme that involves 5,6-cyclic sulfamides. Further intramolecular nucleophilic addition of the sulfamide nitrogen atom to the masked aldehyde group of the monosaccharide in the open chain form afforded the target sugar mimics. By starting from D-glucose and D-mannose precursors, 2-aza-3,3-dioxo-3-thiaindolizidine derivatives with hydroxylation profiles that matched those of (+)-castanospermine and 6-epi-(+)-castanospermine were obtained. In vitro screening against a panel of glycosidases evidenced a high selectivity towards alpha-mannosidase. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2805 / 2808

页数：4

共 31 条

[11] α- and β-Glucosidase inhibitors:: chemical structure and biological activity [J].

de Melo, Eduardo Borges ;

Gomes, Adriane da Silveira ;

Carvalho, Ivone .

TETRAHEDRON, 2006, 62 (44) :10277-10302

[12]

Diaz-Perez P., 2005, EUR J ORG CHEM, P2903

[13] Synthesis and biological evaluation of 6-oxa-nor-tropane glycomimetics as glycosidase inhibitors [J].

Garcia-Moreno, M. Isabel ;

Mellet, Carmen Ortiz ;

Fernandez, Jose M. Garcia .

TETRAHEDRON, 2007, 63 (33) :7879-7884

[14] Synthesis of calystegine B2, B3, and B4 analogues:: Mapping the structure-glycosidase inhibitory activity relationships in the 1-deoxy-6-oxacalystegine series [J].

García-Moreno, MI ;

Mellet, CO ;

Fernández, JMG .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2004, 2004 (08) :1803-1819

[15] Synthesis and evaluation of isourea-type glycomimetics related to the indolizidine and trehazolin glycosidase inhibitor families [J].

García-Moreno, MI ;

Díaz-Pérez, P ;

Mellet, CO ;

Fernández, JMG .

JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (23) :8890-8901

[16] Castanospermine-trehazolin hybrids:: a new family of glycomimetics with tuneable glycosidase inhibitory properties [J].

García-Moreno, MI ;

Díaz-Pérez, P ;

Mellet, CO ;

Fernández, JMG .

CHEMICAL COMMUNICATIONS, 2002, (08) :848-849

[17]

GARCIAMORENO MI, 2000, J ORG CHEM, V65, P136

[18] Gaucher's disease: a paradigm for interventional genetics [J].

Germain, DP .

CLINICAL GENETICS, 2004, 65 (02) :77-86

[19] Cyclic HIV-1 protease inhibitors derived from mannitol: Synthesis, inhibitory potencies, and computational predictions of binding affinities [J].

Hulten, J ;

Bonham, NM ;

Nillroth, U ;

Hansson, T ;

Zuccarello, G ;

Bouzide, A ;

Aqvist, J ;

Classon, B ;

Danielson, UH ;

Karlen, A ;

Kvarnstrom, I ;

Samuelsson, B ;

Hallberg, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (06) :885-897

[20]

Legler G., 1999, IMINOSUGARS GLYCOSID, P31

← 1 2 3 4 →