117781-12-1Relevant articles and documents
A divergent approach for the synthesis of some polyhydroxy pyrrolidines and piperidines from ribosylamine
Chirke, Sahadev S.,Rajender, Anugula,Rao, Batchu Venkateswara
, p. 103 - 109 (2014)
A simple and efficient synthesis of 1,4-dideoxy-1,4-imino-d-ribitol, 1,4-dideoxy-1,4-imino-l-lyxitol, N-benzyl derivative of d-ribitol, 3,4,5-trihydroxy-piperidine, l-4-epi-isofagomine and d-3-epi-isofagomine, which are glycosidase inhibitors has been described from the commercially available d-ribose as a starting material.
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.
A divergent, short, and stereoselective approach to pyrrolidine iminosugars: Synthesis of 1,4-dideoxy-1,4-imino-derivatives of d-allitol, d-ribitol, ethyl-erythritol, and (-)-2,3-trans-3-4-cis-dihydroxyproline
Chirke, Sahadev S.,Rajender, Anugula,Lakshmi, Jerripothula K.,Rao, Batchu Venkateswara
supporting information, p. 1218 - 1221 (2015/03/04)
A highly stereoselective addition of Grignard reagent on lactamine for the synthesis of 1,4-dideoxy-1,4-imino-derivatives of d-allitol, d-ribitol, ethyl-erythritol, and (-)-2,3-trans-3-4-cis-dihydroxyproline has been described from commercially available d-ribose as a starting material.
Effective and one-step stereo-controlled synthesis of benzyloxylated- diiodopentanes for the synthesis of five-membered imino-sugars
Guo, Lina,Liu, Yonghui,Wan, Yue,Wang, Peng George,Zhao, Wei
, p. 2579 - 2582 (2013/06/26)
An effective and stereo-controlled synthesis of 1,3,4-tris(benzyloxy)-2,5- diiodopentane starting from 2,3,5-tris(benzyloxy)pentane-1,4-diol was reported. Synthesis was improved to get the diiodide compound instead of forming the ring-closure product (ben
N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase
Goeminne, Annelies,Berg, Maya,McNaughton, Michael,Bal, Gunther,Surpateanu, Georgiana,Van der Veken, Pieter,Prol, Stijn De,Versees, Wim,Steyaert, Jan,Haemers, Achiel,Augustyns, Koen
, p. 6752 - 6763 (2008/12/21)
A key enzyme within the purine salvage pathway of parasites, nucleoside hydrolase, is proposed as a good target for new antiparasitic drugs. We have developed N-arylmethyl-iminoribitol derivatives as a novel class of inhibitors against a purine specific nucleoside hydrolase from Trypanosoma vivax. Several of our inhibitors exhibited low nanomolar activity, with 1,4-dideoxy-1,4-imino-N-(8-quinolinyl)methyl-d-ribitol (UAMC-00115, Ki 10.8 nM), N-(9-deaza-adenin-9-yl)methyl-1,4-dideoxy-1,4-imino-d-ribitol (Ki 4.1 nM), and N-(9-deazahypoxanthin-9-yl)methyl-1,4-dideoxy-1,4-imino-d-ribitol (Ki 4.4 nM) being the three most active compounds. Docking studies of the most active inhibitors revealed several important interactions with the enzyme. Among these interactions are aromatic stacking of the nucleobase mimic with two Trp-residues, and hydrogen bonds between the hydroxyl groups of the inhibitors and amino acid residues in the active site. During the course of these docking studies we also identified a strong interaction between the Asp40 residue from the enzyme and the inhibitor. This is an interaction which has not previously been considered as being important.
Synthesis and biochemical evaluation of guanidino-alkyl-ribitol derivatives as nucleoside hydrolase inhibitors
Goeminne,McNaughton,Bal,Surpateanu,Van Der Veken,De Prol,Versees,Steyaert,Haemers,Augustyns
, p. 315 - 326 (2008/09/18)
Nucleoside hydrolase (NH) is a key enzyme in the purine salvage pathway. The purine specificity of the IAG-NH from Trypanosoma vivax is at least in part due to cation-π-stacking interactions. Guanidinium ions can be involved in cation-π-stacking interactions, therefore a series of guanidino-alkyl-ribitol derivatives were synthesized in order to examine the binding affinity of these compounds towards the target enzyme. The compounds show moderate to good inhibiting activity towards the IAG-NH from T. vivax.
Enantioselective synthesis of hydroxylated pyrrolidines via Sharpless epoxidation and olefin metathesis
Murruzzu, Caterina,Riera, Antoni
, p. 149 - 154 (2007/10/03)
The enantioselective synthesis of polyhydroxylated pyrrolidines from enantiomerically pure 2,3-epoxy-pent-4-en-1-ol 5 is described herein. The epoxy alcohol, readily available in any configuration by Sharpless epoxidation, was submitted to regioselective C-3 ring-opening with allyl amine, Boc-protection and ring-closing metathesis to yield dehydropyrrole derivative 7. From this key intermediate, 1,4-dideoxy-1,4-imino-d-ribitol (+)-3 and 1,4-dideoxy-1,4-imino-d-allitol (+)-4 were prepared in high yields. The enantiomers of these compounds can be obtained by the same sequence starting from an epoxy alcohol with the opposite configuration.
Chiral oxime ethers in asymmetric synthesis. O-(1-Phenylbutyl)- benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols, α-amino acid derivatives, and 2-hydroxymethyl nitrogen heterocycles including iminosugars
Cooper, Tracey S.,Larigo, Alexander S.,Laurent, Pierre,Moody, Christopher J.,Takle, Andrew K.
, p. 1252 - 1262 (2007/10/03)
Addition of a range of organolithium and Grignard reagents to (E)-O-(1-phenylbutyl)benzyloxyacetaldoxime 1 in the presence of boron trifluoride dietbyl etherate is highly diastereoselective. The resulting hydroxylamines 2 undergo N-O bond cleavage upon treatment with zinc-acetic acid or molybdenum hexacarbonyl to give, after N-protection, protected 1,2-aminoalcohols 3 in high enantiomeric purity. Debenzylation of 3a and 3d gave N-Boc (R)-alaninol and (S)-phenylalaninol respectively. The hydroxylamines 2 also serve as α-amino acid precursors, 2i being converted into N-formyl-(R)-alaninyl-(S)-(4-bromo)phenylalanine ester 7, the N-terminal dipeptide of a natural depsipeptide. The versatility of the 1,2-aminoalcohol derivatives was further illustrated by their conversion into 5-, 6- and 7-membered 2-hydroxymethyl nitrogen heterocycles 15-19 in high enantiomeric excess by a ring-closing metathesis reaction. Further reaction of the dihydropyrrole 15 gave the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol. The Royal Society of Chemistry 2005.
O-(1-phenylbutyl)benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols and 2-hydroxymethyl nitrogen heterocycles
Cooper, Tracey S.,Larigo, Alexander S.,Laurent, Pierre,Moody, Christopher J.,Takle, Andrew K.
, p. 1730 - 1732 (2007/10/03)
Addition of organometallic reagents to O-(1-phenylbutyl)benzyloxyacetaldoxime in the presence of boron trifluoride diethyl etherate is highly diastereoselective; the resulting hydroxylamines are readily converted into protected 1,2-aminoalcohols and 2-hydroxymethyl nitrogen heterocycles, including the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol, in high enantiomeric excess.
Chiral synthesis of both enantiomers of 1,4-dideoxy-1,4-iminolyxitol and 1,4-dideoxy-1,4-iminoribitol
Takano,Moriya,Ogasawara
, p. 681 - 684 (2007/10/02)
Reaction of 2,3-dibromopropionyl chloride with 4-methoxyphenol and (S)-1-methylbenzylamine yielded a 4:5 mixture of readily separable diastereomeric aziridine esters in an excellent yield. Both diastereomers, upon heating with vinylene carbonate, furnished four readily separable diastereomeric pyrrolidine esters, respectively, which were transformed into both enantiomers of 1,4-dideoxy-1,4-iminolyxitol and 1,4-dideoxy-1,4-iminoribitol.
