157363-84-3Relevant articles and documents
Iminosugars: Effects of stereochemistry, ring size, and n-substituents on glucosidase activities
Zamoner, Luís O. B.,Arag?o-Leoneti, Valquiria,Carvalho, Ivone
, (2019/09/03)
N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 μM and 138 μM, respectively, using DNJ as reference (IC50 134 μM). On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 μM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 μM). Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 μM) of the corresponding D-gluco-piperidine miglustat drug (40a). Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 μM.
An efficient approach to 2,5-anhydro-glucitol-based 1′-homo-N- nucleoside mimetics
Bhatt, Beenu,Thomson, Robin J.,Von Itzstein, Mark
scheme or table, p. 2741 - 2743 (2011/06/19)
This Letter describes an efficient synthesis of a range of 1′-homo-N-nucleoside mimetics with a series of 4-substituted 1,2,3-triazoles replacing the natural nucleobase. The synthesis of 6-O-monosulfated 1′-homo-N-nucleoside mimetic derivatives is also discussed.
Polyhydroxylated Piperidines and Azepanes from D-Mannitol. Synthesis of 1-Deoxynojirimycin and Analogues
Poitout, Lydie,Merrer, Yves Le,Depezay, Jean-Claude
, p. 3293 - 3296 (2007/10/02)
D-mannitol and L-iditol bis-epoxides, easily obtained from D-mannitol, are convenient substrates for the synthesis of polyhydroxylated piperidines and azepanes, via a nucleophilic opening of one epoxy function followed by a spontaneous intramolecular ring closure.Using this strategy 1-deoxynojirimycin and analogues were prepared. - Key words: D-mannitol, Piperidine, Azepane, 1-deoxynojirimycin, 1,5-dideoxy-1,5-imino-L-gulitol, β-Glycosidase inhibitor.