100806-53-9Relevant academic research and scientific papers
Synthesis of L-enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides
Satoh, Hiroshi,Yoshimura, Yuichi,Sakata, Shinji,Miura, Shinji,Machida, Haruhiko,Matsuda, Akira
, p. 989 - 992 (1998)
L-Enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides were synthesized from D-xylose. Methyl 2,3,5-tri-O-benzyl-D-xylofuranoside 6 was converted to the corresponding xylitol 7, which was treated with MsCl and then Na2S to give 1,4-anhydro-L-4-thioarabitol 8. As previously reported, Pummerer rearrangement of 8 followed by glycosylation with a silylated thymine and N4-acetylcytosine derivative and deprotection gave the corresponding α- and β-L-4'-thioarabinofuranosyl pyrimidine nucleosides.
Synthesis and Evaluation of Hybrid Structures Composed of Two Glucosylceramide Synthase Inhibitors
Vandenberg, Richard J.B.H.N.,Vanrijssel, Erwin R.,Ferraz, Maria Joao,Houben, Judith,Strijland, Anneke,Donker-Koopman, Wilma E.,Wennekes, Tom,Bonger, Kimberly M.,Ghisaidoobe, Amar B. T.,Hoogendoorn, Sascha,Vandermarel, Gijsbert A.,Codée, Jeroen D. C.,Overkleeft, Herman S.,Aerts, Johannes M. F. G.
, p. 2042 - 2062 (2015/12/23)
Glucosylceramide metabolism and the enzymes involved have attracted significant interest in medicinal chemistry, because aberrations in the levels of glycolipids that are derived from glucosylceramide are causative in a range of human diseases including lysosomal storage disorders, type2 diabetes, and neurodegenerative diseases. Selective modulation of one of the glycoprocessing enzymes involved in glucosylceramide metabolism - glucosylceramide synthase (GCS), acid glucosylceramidase (GBA1), or neutral glucosylceramidase (GBA2) - is therefore an attractive research objective. In this study we took two established GCS inhibitors, one based on deoxynojirimycin and the other a ceramide analogue, and merged characteristic features to obtain hybrid compounds. The resulting 39-compound library does not contain new GCS inhibitors; however, a potent (200nm) GBA1 inhibitor was identified that has little activity toward GBA2 and might therefore serve as a lead for further biomedical development as a selective GBA1 modulator. Taking the best of both: Two established glucosylceramide synthase (GCS) inhibitors were merged via convergent synthesis to obtain hybrid compounds. Members of this 39-compound library have characteristics of both parent GCS inhibitors. No new GCS inhibitors were established, but a potent (200nm) acid glucosylceramidase (GBA1) inhibitor was identified. This adamantanemethyloxypenanoic acid pyrrolidene-substituted derivative of eliglustat can serve as a lead for further biomedical development of selective GBA1 modulators.
GLYCOSIDASE INHIBITORS AND METHODS OF SYNTHESIZING SAME
-
Page/Page column 5, (2010/11/28)
The compounds of the present invention relate to chain-extended and chain-modified analogues of salacinol, including embodiments where the sulfate moiety has been substituted with a carboxylate or phosphate moiety. In other embodiments the sulfate moiety has been shifted by one carbon atom in the zwitterionic structure. In another embodiment the polyhydroxylated side chain may be replaced with a lipophilic alkyl chain and a suitable counterion. The invention also encompasses methods for synthesizing the salacinol analogues and using the analogues for enzyme inhibition applications.
THE SYNTHESIS FROM D-XYLOSE OF THE POTENT AND SPECIFIC ENANTIOMERIC GLUCOSIDASE INHIBITORS, 1,4-DIDEOXY-1,4-IMINO-D-ARABINITOL AND 1,4-DIDEOXY-1,4-AMINO-L-ARABINITOL
Fleet, George W. J.,Smith, Paul W.
, p. 5685 - 5692 (2007/10/02)
Both enantiomers of 1,4-dideoxy-1,4-iminoarabinitol are specific inhibitors of glucosidases.The synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol involves connecting C2 and C5 of xylose together with nitrogen, whereas the synthesis of 1,4-dideoxy-1,4-imino-
POTENT COMPETITIVE INHIBITION OF &α-GALACTOSIDASE AND &α-GLUCOSIDASE ACTIVITY BY 1,4-DIDEOXY-1,4-IMINOPENTITOLS: SYNTHESES OF 1,4-DIDEOXY-1,4-IMINO-D-LYXITOL AND OF BOTH ENANTIOMERS OF 1,4-DIDEOXY-1,4-IMINOARABINITOL
Fleet, G. W. J.,Nicholas, S. J.,Smith, P. W.,Evans, S. V.,Fellows, L. E.,Nash, R. J.
, p. 3127 - 3130 (2007/10/02)
The syntheses of 1,4-dideoxy-1,4-imino-D-lyxitol (3), 1,4-dideoxy-1,4-imino-D-arabinitol (4) and 1,4-dideoxy-1,4-imino-L-arabinitol (5) are reported; (3) is a potent competitive inhibitor of α-galactosidase (green coffee beans) and (4) a competitive inhibitor of α-glucosidase (Brewer's yeast) suggesting that iminopentitols have considerable potential as glycosidase inhibitors. (4) was found to be identical to an alkaloid recently isolated from Angylocalyx boutiqueanus.
