155501-85-2Relevant articles and documents
Bioconversion of N-butylglucamine to 6-deoxy-6-butylamino sorbose by Gluconobacter oxydans
Landis, Bryan H.,McLaughlin, Joseph K.,Heeren, Robert,Grabner, Roy W.,Wang, Ping T.
, p. 547 - 552 (2002)
Gluconobacter oxydans has the unique ability to regioselectively and rapidly oxidize sorbitol and other erythro saccharides. In this report a new process is described by which N-butylglucamine is regioselectively oxidized by the organism. A largescale process is described by which N-butylglucamine can be converted to an intermediate (6-deoxy-6-butylaminosorbose) which can be readily converted to N-butyldeoxynojirimycin by catalytic hydrogenation. The primary process variables of temperature, pH, and added acids and salts were investigated in laboratory bioreactors. Since degradation of the sorbose product was rapid above room temperature, significant enhancement of the selectivity was achieved by lowering the temperature at which the bioconversion was run. The optimum temperature for this conversion was 12-15°C. The pH maximum of the bioconversion was 5.5-6.0. However, the small gain in rate relative to pH 5.0 was at least offset by the increase in degradation of the product at the higher pH. Nitrate salts of N-butylglucamine could replace chloride salts, but sulfate, acetate, and phosphate salts could not. Sulfate in particular led to inhibition of the conversion, while phosphate and acetate led to increased degradation. At temperatures in the range of 12-15°C, pH of around 5.0 and substrate concentrations of 0.2 M, Gluconobacter oxydans catalyzed bioconversion to 6-deoxy-6-butylaminosorbose with yields approaching 95%. These conditions were used to scale this process to 5500-L scale.
N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease
D'Alonzo, Daniele,De Fenza, Maria,Porto, Caterina,Iacono, Roberta,Huebecker, Mylene,Cobucci-Ponzano, Beatrice,Priestman, David A.,Platt, Frances,Parenti, Giancarlo,Moracci, Marco,Palumbo, Giovanni,Guaragna, Annalisa
, p. 9462 - 9469 (2017)
The highly stereocontrolled de novo synthesis of l-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. l-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor.
A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase
Lahav, Dani?l,Liu, Bing,Van Den Berg, Richard J.B.H.N.,Van Den Nieuwendijk, Adrianus M. C. H.,Wennekes, Tom,Ghisaidoobe, Amar T.,Breen, Imogen,Ferraz, Maria J.,Kuo, Chi-Lin,Wu, Liang,Geurink, Paul P.,Ovaa, Huib,Van Der Marel, Gijsbert A.,Van Der Stelt, Mario,Boot, Rolf G.,Davies, Gideon J.,Aerts, Johannes M. F. G.,Overkleeft, Herman S.
supporting information, p. 14192 - 14197 (2017/10/17)
Human nonlysosomal glucosylceramidase (GBA2) is one of several enzymes that controls levels of glycolipids and whose activity is linked to several human disease states. There is a major need to design or discover selective GBA2 inhibitors both as chemical tools and as potential therapeutic agents. Here, we describe the development of a fluorescence polarization activity-based protein profiling (FluoPol-ABPP) assay for the rapid identification, from a 350+ library of iminosugars, of GBA2 inhibitors. A focused library is generated based on leads from the FluoPol-ABPP screen and assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA), and the cytosolic retaining β-glucosidase, GBA3. Our work, yielding potent and selective GBA2 inhibitors, also provides a roadmap for the development of high-throughput assays for identifying retaining glycosidase inhibitors by FluoPol-ABPP on cell extracts containing recombinant, overexpressed glycosidase as the easily accessible enzyme source.
One pot oxidative dehydration - oxidation of polyhydroxyhexanal oxime to polyhydroxy oxohexanenitrile: A versatile methodology for the facile access of azasugar alkaloids
Khobare, Sandip R.,Gajare, Vikas,Reddy, E. Vishnuvardhan,Datrika, Rajender,Banda, Malavika,Siddaiah, Vidavalur,Pachore, Sharad S.,Timanna, Upadhya,Dahanukar, Vilas H.,Syam Kumar
, p. 1 - 6 (2016/09/28)
A unique oxidative dehydration-oxidation of polyhydroxy-oxime (7) to the corresponding ketonitrile (8) in one pot is reported for the first time in carbohydrate literature. Key ketonitrile intermediate (8) upon palladium hydroxide mediated cascade reaction afforded 1-deoxynojirimycin (DNJ) 1b in moderate diastereoselectivity. The cascade reaction involves the conversion of nitrile to amine, heteroannulation, reduction of the imine and subsequent debenzylation to furnish the azasugars. This oxidative dehydration-oxidation and reductive heteroannulation methodology is successfully utilized for the total synthesis of 1-deoxynojirimycin (1b), miglitol (2) and miglustat (3).
