36199-02-7Relevant academic research and scientific papers
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.
Synthesis of polyhydroxylated pyrrolidines from sugar-derived bromonitriles through a cascade addition of allylmagnesium bromide/cyclization/reduction
Malik, Micha?,Jarosz, S?awomir
, p. 1764 - 1776 (2016/02/09)
The synthesis of polyhydroxylated 2-allylpyrrolidines from sugar-derived bromonitriles in a cascade addition of allylmagnesium bromide/SN2 cyclization/reduction with Zn(BH4)2 is described. The stereochemical course of the
Simple and efficient synthesis of 2,5-anhydro-d-glucitol
Arag?o-Leoneti, Valquiria,Carvalho, Ivone
, p. 1087 - 1089 (2013/04/10)
The synthesis of 2,5-anhydro-d-glucitol is described via intramolecular cyclization of diepoxide using ammonium formate in MeOH by a microwave-assisted reaction. The overall yield was 32% from d-mannitol derivative involving seven steps.
Stereoselective synthesis of 3-amino-3-deoxy-aldohexoses by aldol condensation of tricarbonyliron-α-Aminodienone complexes: Total synthesis of multiprotected kanosamine
Miesch, Laurence,Welsch, Tania,Toupet, Loic
experimental part, p. 161 - 167 (2011/03/19)
An aldol reaction between the divalent tin enol ether of racemic N-Boc α-aminodienone-tricarbonyliron complex and multiprotected d-glyceraldehyde provided predominantly two enantiomerically pure ketol diastereoisomers. From there, multiprotected kanosamin
Mannitol bis-phosphate based inhibitors of fructose 1,6-bisphosphate aldolases
Mabiala-Bassiloua, Charles-Gabin,Arthus-Cartier, Guillaume,Hannaert, Veronique,Therisod, Helene,Sygusch, Jurgen,Therisod, Michel
supporting information; experimental part, p. 804 - 808 (2011/12/16)
Several 5-O-alkyl- and 5-C-alkyl-mannitol bis-phosphates were synthesized and comparatively assayed as inhibitors of fructose bis-phosphate aldolases (Fbas) from rabbit muscle (taken as surrogate model of the human enzyme) and from Trypanosoma brucei. A l
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.
Direct selective and controlled protection of multiple hydroxyl groups in polyols via iterative regeneration of stannylene acetals
Simas, Alessandro B.C.,da Silva, Angelo A.T.,dos Santos Filho, Tarcizio J.,Barroso, Pedro T.W.
supporting information; experimental part, p. 2744 - 2746 (2009/09/25)
A direct selective protection (O-benzylation) of two or more hydroxyl groups in polyols displaying diverse structural patterns was made possible by the establishment of conditions that enable an efficient turnover for the Bu2Sn group, initially
Synthesis of chiral hydroxyl phospholanes from D-mannitol and their use in asymmetric catalytic reactions
Li, Wenge,Zhang, Zhaoguo,Xiao, Dengming,Zhang, Xumu
, p. 3489 - 3496 (2007/10/03)
Chiral hydroxyl monophosphane 3 [(2S,3S,4S,5S)-3,4-dihydroxy-2,5-dimethyl-1-phenylphospholane] and bisphospholanes 5a [1,2-bis[(2S,3S,4S,5S)-3,4-dihydroxy-2,5-dimethylphospholanyl]benzene] and 5b [1,2-bis[(2S,3S,4S,5S)-2,5-diethyl-3,4-dihydroxyphospholanyl]benzene] were synthesized from readily available D-mannitol in high yields. Strategies for protection and deprotection of OH-groups in the presence of phosphines have been explored. Rate acceleration in the Baylis - Hillman reaction was observed when a hydroxyl phosphine was used as the catalyst. Rhodium complexes with chiral bisphospholanes are highly enantioselective catalysts for the asymmetric hydrogenation of various kinds of functionalized olefins such as dehydroamino acid derivatives, itaconic acid derivatives, and enamides. An interesting feature of the hydroxyl phospholane system is that hydrogenation of some substrates can be carried out in water with >99% ee and 100% conversion (e.g., itaconic acid).
Synthesis of amphiphilic polyhydroxylated pyrrolidines as potential glycosidase inhibitors
Esposito, Annamaria,Falorni, Massimo,Taddei, Maurizio
, p. 6543 - 6546 (2007/10/03)
Several polyhydroxylated pyrrolidines with an aliphatic long chain on the ring nitrogen were prepared starting from D-mannitol. An amphiphilic bis- azasugar scaffold has been also prepared. These products behave as cationic surfactants and show a promising anti HIV-1 activity.
An efficient conversion of D-mannitol into D-fructose and 1,5-dideoxy-1,5-imino-D-mannitol (1-deoxymannojirimycin)
Zou, Wei,Szarek, Walter A.
, p. 25 - 34 (2007/10/02)
The utility of bis(tributyltin)oxide-bromine for the selective oxidation of secondary hydroxyl groups in the presence of primary hydroxyl groups has been further demonstrated by the efficient conversions of D-mannitol into D-fructose and 1,5-dideoxy-1,5-imino-D-mannitol (1-deoxymannojirimycin).
