Synthesis of hybrids of d-glucose and d-galactose with 1-deoxynojirimycin analogues using ring-closing metathesis (original) (raw)
Synthesis of 1-deoxy-l-gulonojirimycin (l-guloDNJ) and 1-deoxy-d-talonojirimycin (d-taloDNJ)
Carbohydrate Research, 2002
Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5-dideoxy-1,5-imino-L-gulitol (L-guloDNJ) and 1,5-dideoxy-1,5-imino-L-talitol (L-taloDNJ) are reported, from D-mannose and D-fructose, respectively. The key steps in both syntheses involved reductive aminative cyclizations. Thus, L-gulo DNJ was obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-O-p-toluenesulfonyl-D-mannononitrile with LiAlH 4 in DME to give the protected azasugar which upon hydrolysis with HCl afforded crystalline L-gulo DNJ as the HCl salt in 29% overall yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-b-D-ribohexulofuranose obtained from D-fructose in six steps, followed by treatment with HCl, afforded L-talo DNJ as an HCl salt in 10% overall yield.
Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors
Beilstein Journal of Organic Chemistry, 2010
N-Alkylation at the ring nitrogen of the D-galactosidase inhibitor 1-deoxygalactonojirimycin with a functionalised C 6 alkyl chain followed by modification with different aromatic substituents provided lipophilic 1-deoxygalactonojirimycin derivatives which exhibit inhibitory properties against β-glycosidases from E. coli and Agrobacterium sp. as well as green coffee bean α-galactosidase. In preliminary studies, these compounds also showed potential as chemical chaperones for GM1-gangliosidosis related β-galactosidase mutants.
Rational design of aza sugars via biocatalysis: mannojirimycin and other glycosidase inhibitors
The Journal of Organic Chemistry, 1993
Mannojirymicin 2a, its C-5 epimer 13, and mannosidase inhibitor 3a have been synthesized from chlorobenzene via enzymatic hydroxylation followed by stereoselective amination and oxidative cleavage of the l-chlorocyclohexa-4,S-diene-2,3-diol. Compounds that selectively inhibit glycosidases have attracted interest because of the significance of such inhibition to both viral expression' and tumor growth.2
Bioorganic & Medicinal Chemistry Letters, 2004
As potential lead structures for a new class of glycosidase inhibitors the novel O-glycosyl amino acid mimetics 3 0-O-[2,6anhydro-d-glycero-l-gluco-heptitol-1-yl]-l-serine 3 and-l-threonine 4 were synthesized, employing regio-and stereoselective aziridine ring opening methodology. They proved to be stable in the presence of glycosidases and showed competitive inhibition of agalactosidase from Aspergillus niger.