- N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines
-
1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The
- Zhou, Jian,Negi, Arvind,Mirallai, Styliana I.,Warta, Rolf,Herold-Mende, Christel,Carty, Michael P.,Ye, Xin-Shan,Murphy, Paul V.
-
p. 418 - 433
(2019/01/03)
-
- In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 α-L-fucosidases
-
GH29 α-L-fucosidases catalyze the hydrolysis of α-L-fucosidic linkages. Deficiency in human lysosomal α-L-fucosidase (FUCA1) leads to the recessively inherited disorder, fucosidosis. Herein we describe the development of fucopyranose-configured cyclophellitol aziridines as activity-based probes (ABPs) for selective in vitro and in vivo labeling of GH29 α-L-fucosidases from bacteria, mice and man. Crystallographic analysis on bacterial α-L-fucosidase confirms that the ABPs act by covalent modification of the active site nucleophile. Competitive activity-based protein profiling identified l-fuconojirimycin as the single GH29 α-L-fucosidase inhibitor from eight configurational isomers.
- Jiang, Jianbing,Kallemeijn, Wouter W.,Wright, Daniel W.,Van Den Nieuwendijk, Adrianus M. C. H.,Rohde, Veronica Coco,Folch, Elisa Colomina,Van Den Elst, Hans,Florea, Bogdan I.,Scheij, Saskia,Donker-Koopman, Wilma E.,Verhoek, Marri,Li, Nan,Schürmann, Martin,Mink, Daniel,Boot, Rolf G.,Codée, Jeroen D. C.,Van Der Marel, Gijsbert A.,Davies, Gideon J.,Aerts, Johannes M. F. G.,Overkleeft, Herman S.
-
p. 2782 - 2789
(2015/09/02)
-
- Deoxygenative olefination reaction as the key step in the syntheses of deoxy and iminosugars
-
Just a spoonful of sugar! A new synthetic strategy involving the use of a deoxygenative olefination reaction as the key step was developed for the preparation of deoxy and iminosugars in their optically active form (see scheme). This strategy has been proven successful by the use of a pentose, hexose, heptose, and disaccharide as the starting materials. Furthermore, it was applied in a formal total synthesis of iminosugar (-)-1-deoxy-l- fuconojirimycin, which can inhibit a-l-fucosidase.
- Hsu, Yung Chang,Hwu, Jih Ru
-
p. 7686 - 7690
(2012/09/07)
-
- Asymmetric synthesis of the L-fuco-nojirimycin, a nanomolar α-L-fucosidase inhibitor
-
We describe the asymmetric synthesis of the 5-amino-5-deoxy-l-fucose (l-fuco-nojirimycin) which appears as a very potent fucosidase inhibitor with a Ki value of 1 nM.
- Dubernet, Mathieu,Defoin, Albert,Tarnus, Celine
-
p. 1172 - 1174
(2007/10/03)
-
- Looking glass inhibitors: Efficient synthesis and biological evaluation of D-deoxyfuconojirimycin
-
1,6-Dideoxygalactostatin, the mirror image of 1-deoxy-L-fuconojirimycin, was efficiently prepared from 2,3-O-isopropylidene-L-lyxonolactone in four steps and evaluated as a glycosidase inhibitor.
- Bleriot, Yves,Gretzke, Dirk,Kruelle, Thomas M.,Butters, Terry D.,Dwek, Raymond A.,Nash, Robert J.,Asano, Naoki,Fleet, George W.J.
-
p. 2713 - 2718
(2007/10/03)
-
- Glycosidase inhibitors: Synthesis of enantiomerically pure aza-sugars from Schiff base amino esters via tandem reduction-alkenylation and osmylation
-
Nitrogen-in-the-ring 'aza-sugars' have been synthesized in enantiomerically pure form from the amino acid L-alanine in excellent overall yield. The O'Donnell's Schiff base of L-alanine methyl ester 9a was converted to aza-sugar L-fuco-1-deoxy-nojirimycin, 18, and to the epimer L-gulo-1- deoxy-nojirimycin, 20, in eight steps. The overall yields were 20 and 29%, respectively. The methodology for the efficient generation of silyl- and benzyl-protected (E)-3-lithio-2-propen-1-ols, and the use of these alkenyllithiums with iBu5Al2H as nucleophiles in the threo-selective tandem reduction-alkenylation of the Schiff base esters is described. Osmium- catalyzed cis-oxygenation of the resulting olefin products was selective for the galacto (fuco) amino polyols in all cases for the acyclic olefins, and was gulo-selective for the cyclic D-4,5-dihydropyridine pivalate, 17c. TEMPO- NaOCl was selective for oxidation of the primary position of the acyclic Schiff bases, and allowed for minimal protection/deprotection of the intermediates. The resulting N-benzhydryl heterocycles were easily deprotected with H2-Pd at atmospheric pressure.
- Polt, Robin,Sames, Dalibor,Chruma, Jason
-
p. 6147 - 6158
(2007/10/03)
-
- Simple syntheses of L-fucopyranose and fucosidase inhibitors utilizing the highly stereoselective methylation of an arabinofuranoside 5-urose derivative
-
The simple syntheses of L-fucopyranose 1 and its three analogues 2-4 are described. A key reaction is a stereocontrolled elongation by one carbon unit at the side chain of an α-D-arabino-pentodialdo-1,4-furanoside 9 with MeMgI-ZnCl2 or Me3Al. Diastereofacial selectivities of more than 92% were achieved.
- Takahashi, Shunya,Kuzuhara, Hiroyoshi
-
p. 607 - 612
(2007/10/03)
-
- Syntheses of L-Fucopyranose and Its Homologs with Ring Heteroatoms Other than Oxygen. Sterocontrolled Conversion of the Common D-Arabinofuranoside Intermediate
-
L-Fucopyranose and a couple of L-fucosidase inhibitors, 5-deoxy-5-thio-L-fucopyranose and 1,5-dideoxy-1,5-imino-L-fucitol, were prepared from a common pentose intermediate with α-D-arabino configuration.Stereoselectivities on carbon chain elongation of th
- Takahashi, Shunya,Kuzuhara, Hiroyoshi
-
-
- Fluorinated 1,5-Dideoxy-1,5-iminoalditols: Synthesis of 1,5,6-Trideoxy-6-fluoro-1,5-imino-D-glucitol (1,6-Dideoxy-6-fluoronojirimycin) and 1,4,5-Trideoxy-4-fluoro-1,5-imino-D-ribitol (1,2,5-Trideoxy-2-fluoro-1,5-imino-L-ribitol)
-
An efficient synthesis of 1,5,6-trideoxy-6-fluoro-1,5-imino-D-glucitol 13 from inexpensive L-sorbose by way of reductive amination of 12 is described.Synthesis of 1,4,5-trideoxy-4-fluoro-1,5-imino-D-ribitol (1,2,5-trideoxy-2-fluoro-1,5-imino-L-ribitol) 19
- Di, Jie,Rajanikanth, Bandaru,Szarek, Walter A.
-
p. 2151 - 2154
(2007/10/02)
-
- Short efficient synthesis of the α-L-fucosidase inhibitor, deoxyfuconojirimycin [1,5-dideoxy-1,5-imino-l-fucitol] from d-lyxonolactone
-
The only protection required in a five-step synthesis of the α-L-fucosidase inhibitor, deoxyfuconojirimycin [1,5-dideoxy-1,5-imino-L- fucitol] from D-lyxonolactone, a readily available chiral pool material, is a single isopropylidene group.
- Fleet, George W. J.,Petursson, Sigthor,Campbell, Arthur L.,Mueller, Richard A.,Behling, James R.,Babiak, Kevin A.,Ng, John S.,Scaros, Mike G.
-
p. 665 - 666
(2007/10/02)
-
- Monosaccharides Containing Nitrogen in the Ring, XXXVIII. - Synthesis of the α-L-Fucosidase Inhibitor 1,5-Dideoxy-1,5-imino-L-fucitol and of Some of its Derivatives
-
The reaction of 2-azido-2-deoxy-D-galactopyranose (1) with 1,3-propanedithiol yields the open-chained dithioacetal 2, which can be converted to 2-azido-3,4,5-tri-O-benzoyl-2-deoxy-6-O-(methylsulfonyl)-D-galactose trimethylene dithioacetal (9) via 5 and 6.
- Paulsen, Hans,Matzke, Michael
-
p. 1121 - 1126
(2007/10/02)
-
- Synthesis from D-Glucose of 1,5-Dideoxy-1,5-imino-L-fucitol, a Potent &α-L-Fucosidase Inhibitor
-
1,5-Dideoxy-1,5-imino-L-fucitol (1), sythesised from methyl α-D-glucopyranoside, is a potent competitive inhibitor of the hydrolysis of p-nitrophenyl α-L-fucopyranoside catalysed by α-L-fucosidase (ex. bovine epididymis) causing 50percent inhibition of en
- Fleet, George W. J.,Shaw, Antony N.,Evans, Stephen V.,Fellows, Linda E.
-
p. 841 - 842
(2007/10/02)
-
