104292-65-1Relevant academic research and scientific papers
Iminosugar-based galactoside mimics as inhibitors of galactocerebrosidase: SAR studies and comparison with other lysosomal galactosidases
Biela-Banas, Anna,Ouladi, Farah,Front, Sophie,Gallienne, Estelle,Ikeda-Obatake, Kyoko,Asano, Naoki,Wenger, David A.,Martin, Olivier R.
, p. 2647 - 2652 (2014)
Several families of iminosugar-based galactoside mimics were designed, synthesized, and evaluated as galactocerebrosidase (GALC) inhibitors. They were also tested as inhibitors of lysosomal β- and α-galactosidases in order to find new potent and selective pharmacological chaperones for treatment of the lysosomal storage disorder, Krabbe disease. Whereas 1-C-alkyl imino-l-arabinitols are totally inactive toward the three enzymes, 1-C-alkyl imino-L-galactitols were found to be active only toward α-galactosidase A. Finally, 1-N-iminosugars provided the best results, as 4-epi-isofagomine was found to be a good inhibitor of both lysosomal β-galactosidase and GALC. Further elaboration of this structure is required to achieve selectivity between these two galactosidases.
Synthesis and Conformation of Pentopyranoside Nucleoside Phosphonates
Li, Xiaochen,Dumbre, Shrinivas G.,Lescrinier, Eveline,Groaz, Elisabetta,Herdewijn, Piet
, p. 6589 - 6603 (2019)
In contrast to natural nucleosides, where the nucleobase is positioned at the anomeric center, we report the synthesis of pentopyranoside nucleosides with a phosphonate functionality at the 1′-anomeric oxygen. Starting from l-arabinose, key functionalized l-glycero- A nd l-erythro-pentopyranose carbohydrate synthons were prepared and further elaborated into the final six-membered ring nucleosides via nucleobase incorporation and phosphonomethylation reactions. NMR analysis demonstrated that these nucleoside phosphonates exist in solution as conformers predominantly adopting a chair structure in which the base moiety is equatorially positioned. Such conformation prevents unfavorable 1,3-diaxial steric and electronic interactions. Notably, the stereochemical outcome of the Vorbrüggen glycosylation step utilized en route to the thymine analogue clearly suggests the absence of anchimeric assistance, as opposed to what is usually observed during nucleoside synthesis using protected furanose precursors. The finding that the diphosphates of the compounds developed in this study are recognized by DNA polymerases is important in view of the future selection of artificial genetic systems and dedicated polymerases as well as applications in therapy.
Chiral Multifunctional Isoprene Units by Ring-Contraction of Riboside Oxiranes
Sundin, Anders,Frejd, Torbjoern,Magnusson, Goeran
, p. 3927 - 3930 (2007/10/02)
Lithium bromide induced ring-contraction of benzyl 2,3- and 3,4-anhydro-β-D(and L)-ribopyranoside (1 and 4) in HMPA/toluene or tetramethylurea (TMU)/toluene gave (R)(and S)-2-(benzyloxy)-2,5-dihydrofufan-4-carboxaldehyde (2 and 5) together with a small amount of benzyl 4-bromo-4-deoxy-β-L(and D)-lyxopyranoside (3 and 6).The latter compound was formed with lithium bromide in 1,1,1-trichloroethane.Benzyl 2,3- and 3,4-anhydro-2-deuterio-β-L-ribopyranoside (4d and 8d) gave the deuterated aldehyde 5d, which carried a vinylic deuterium atom, wheraes benzyl 2,3-anhydro-4-deuterio-β-L-ribopyranoside (4d' ) gave the nondeuterated aldehyde 5.On the basis of these experiments, the mechanism of the ring-contraction as postulated.
