Synthesis of d-galacto-1-deoxynojirimycin (1,5-dideoxy-1,5-imino-d-galactitol) starting from 1-deoxynojirimycin

Heiker, Fred-Robert; Schueller, Alfred Matthias

doi:10.1016/0008-6215(90)80031-w

Cited by 23 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The preparation of the D-galacto isomers of 1 and 5 (4 and 7, respectively) was achieved by the chemical epimerization of the 4-OH group according to the method of Heiker and Scheller. 29 Inhibition of Mammalian -Glucosidases. The IC50 values of nitrogen-in-the-ring pyranoses and furanoses against various mammalian -glucosidases are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Nitrogen-in-the-Ring Pyranoses and Furanoses: Structural Basis of Inhibition of Mammalian Glycosidases

Asano¹,

Oseki²,

Kizu³

et al. 1994

J. Med. Chem.

160

View full text Add to dashboard Cite

Seven pyranoses and three furanoses with a nitrogen in the ring were prepared by chemical synthesis, microbial conversion, and isolation from plants to investigate the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases. The seven pyranoses are 1-deoxynojirimycin (1), the D-manno (2), D-allo (3), and D-galacto (4) isomers of 1, fagomine (1,2-dideoxynojirimycin, 5), and the D-allo (6) and D-galacto (7) isomers of 5, while the three furanoses are 2,5-dideoxy-2,5-imino-D-mannitol (8), 1,4-dideoxy-1,4-imino-D-arabinitol (9), and 1,4-dideoxy-1,4-imino-D-ribitol (10). The 2-deoxygenation and/or 3-epimerization of 1 enhanced the potency for rat intestinal lactase and bovine liver cytosolic beta-galactosidase. Especially compound 6 showed a potent inhibitory activity against both enzymes, and compound 8, a mimic of beta-D-fructofuranose, was a potent inhibitor of both beta-galactosidases as well. Compound 4, which has been known as a powerful alpha-galactosidase inhibitor, exhibited no significant inhibitory activity for most of mammalian beta-galactosidases. In addition, compound 6 fairly retained a potency of 1 toward rat intestinal isomaltase. In this study, compound 8, known as a processing alpha-glucosidase I inhibitor in cell culture, has been found to have no effect on processing alpha-glucosidase II, whereas 9 has been shown to be a good nonspecific inhibitor of intestinal isomaltase, processing alpha-glucosidase II, Golgi alpha-mannosidases I and II, and porcine kidney trehalase. It has been speculated that glycosidase inhibitors have structures which resemble those of the respective glycosyl cations. This Broad inhibitory activity of 9 toward various glycosidases suggest that it superimposes well on the various glycosyl cations.

show abstract

Section: Resultsmentioning

confidence: 99%

Nitrogen-in-the-Ring Pyranoses and Furanoses: Structural Basis of Inhibition of Mammalian Glycosidases

Asano¹,

Oseki²,

Kizu³

et al. 1994

J. Med. Chem.

160

View full text Add to dashboard Cite

show abstract

“…1‐Deoxy‐3‐ epi ‐nojirimycin ( allo ‐DNJ) ( 3 ) was prepared by the microbial redox reaction at C‐3 of the N ‐benzyloxycarbonyl derivative of DNJ as described previously [16]. 1‐Deoxygalactonojirimycin ( 4 ) and 1,2‐dideoxygalactonojirimycin ( 6 ) were prepared by the chemical epimerization of the 4‐OH group of 1 and fagomine, respectively, according to the literature [17]. α‐Homonojirimycin (α‐HNJ) ( 7 ), α‐homomannojirimycin (α‐ manno ‐HNJ) ( 8 ) and α‐homoallonojirimycin (α‐ allo ‐HNJ) ( 9 ) were isolated from the whole plant of Aglaonema treubii (Araceae) as reported previously [18].…”

Section: Methodsmentioning

confidence: 99%

“…1-Deoxy-3-epinojirimycin (allo-DNJ) (3) was prepared by the microbial redox reaction at C-3 of the N-benzyloxycarbonyl derivative of DNJ as described previously [16]. 1-Deoxygalactonojirimycin (4) and 1,2-dideoxygalactonojirimycin (6) were prepared by the chemical epimerization of the 4-OH group of 1 and fagomine, respectively, according to the literature [17].…”

Section: Inhibitorsmentioning

confidence: 99%

In vitro inhibition and intracellular enhancement of lysosomal α‐galactosidase A activity in Fabry lymphoblasts by 1‐deoxygalactonojirimycin and its derivatives

Asano¹,

Ishii²,

Kizu³

et al. 2000

European Journal of Biochemistry

235

135

View full text Add to dashboard Cite

Fabry disease is a lysosomal storage disorder caused by deficient lysosomal alpha-galactosidase A (alpha-Gal A) activity. Deficiency of the enzyme activity results in progressive deposition of neutral glycosphingolipids with terminal alpha-galactosyl residue in vascular endothelial cells. We recently proposed a chemical chaperone therapy for this disease by administration of 1-deoxygalactonojirimycin, a potent inhibitor of the enzyme, at subinhibitory intracellular concentrations [Fan, J.-Q., Ishii, S., Asano, N. and Suzuki, Y. (1999) Nat. Med. 5, 112-115]. 1-Deoxygalactonojirimycin served as a specific chaperone for those mutant enzymes that failed to maintain their proper conformation to avoid excessive degradation. In order to establish a correlation between in vitro inhibitory activity and intracellular enhancement activity of the specific chemical chaperone, a series of 1-deoxygalactonojirimycin derivatives were tested for activity with both alpha-Gal A and Fabry lymphoblasts. 1-Deoxygalactonojirimycin was the most potent inhibitor of alpha-Gal A with an IC50 value of 0.04 microM. alpha-Galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin were effective inhibitors with IC50 values of 0.21, 4.3 and 16 microM, respectively. N-Alkylation, deoxygenation at C-2 and epimerization at C-3 of 1-deoxygalactonojirimycin markedly lowered or abolished its inhibition toward alpha-Gal A. Inclusion of 1-deoxygalactonojirimycin, alpha-galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin at 100 microM in culture medium of Fabry lymphoblasts increased the intracellular alpha-Gal A activity by 14-fold, 5.2-fold, 2.4-fold and 2.3-fold, respectively. Weaker inhibitors showed only a minimum enhancement effect. These results suggest that more potent inhibitors act as more effective specific chemical chaperones for the mutant enzyme, and the potent competitive inhibitors of alpha-Gal A are effective specific chemical chaperones for Fabry disease.

show abstract

“…This resulted in the smooth formation of 4- epi -fagomine ( 4 ) in 92% yield, thus completing this remarkably efficient six-step synthesis with an overall yield of 52%. 4- epi -Fagomine has been prepared on several other occasions. − The first synthesis required 10 steps from 3 using the method of Heiker and Schueller (no yield reported), and the synthesis with the best reported yield (28%) proceeded via an asymmetric route from a benzyl-protected galactal . Although the need for a protecting group here was unavoidable because of the inherent reactivity of the galacto configuration, protecting group manipulation added just one step to the synthesis, and an expedient synthesis of 4 was achieved with the best yield to date.…”

Section: Resultsmentioning

confidence: 99%

Applications and Limitations of the I₂-Mediated Carbamate Annulation for the Synthesis of Piperidines: Five- versus Six-Membered Ring Formation

et al. 2013

View full text Add to dashboard Cite

A protecting-group-free synthetic strategy for the synthesis of piperidines has been explored. Key in the synthesis is an I2-mediated carbamate annulation, which allows for the cyclization of hydroxy-substituted alkenylamines into piperidines, pyrrolidines, and furans. In this work, four chiral scaffolds were compared and contrasted, and it was observed that with both d-galactose and 2-deoxy-d-galactose as starting materials, the transformations into the piperidines 1-deoxygalactonorjirimycin (DGJ) and 4-epi-fagomine, respectively, could be achieved in few steps and good overall yields. When d-glucose was used as a starting material, only the furan product was formed, whereas the use of 2-deoxy-d-glucose resulted in reduced chemo- and stereoselectivity and the formation of four products. A mechanistic explanation for the formation of each annulation product could be provided, which has improved our understanding of the scope and limitations of the carbamate annulation for piperidine synthesis.

show abstract

Synthesis of d-galacto-1-deoxynojirimycin (1,5-dideoxy-1,5-imino-d-galactitol) starting from 1-deoxynojirimycin

Cited by 23 publications

References 19 publications

Nitrogen-in-the-Ring Pyranoses and Furanoses: Structural Basis of Inhibition of Mammalian Glycosidases

Nitrogen-in-the-Ring Pyranoses and Furanoses: Structural Basis of Inhibition of Mammalian Glycosidases

In vitro inhibition and intracellular enhancement of lysosomal α‐galactosidase A activity in Fabry lymphoblasts by 1‐deoxygalactonojirimycin and its derivatives

Applications and Limitations of the I₂-Mediated Carbamate Annulation for the Synthesis of Piperidines: Five- versus Six-Membered Ring Formation

Contact Info

Product

Resources

About

Synthesis of d-galacto-1-deoxynojirimycin (1,5-dideoxy-1,5-imino-d-galactitol) starting from 1-deoxynojirimycin

Cited by 23 publications

References 19 publications

Nitrogen-in-the-Ring Pyranoses and Furanoses: Structural Basis of Inhibition of Mammalian Glycosidases

Nitrogen-in-the-Ring Pyranoses and Furanoses: Structural Basis of Inhibition of Mammalian Glycosidases

In vitro inhibition and intracellular enhancement of lysosomal α‐galactosidase A activity in Fabry lymphoblasts by 1‐deoxygalactonojirimycin and its derivatives

Applications and Limitations of the I2-Mediated Carbamate Annulation for the Synthesis of Piperidines: Five- versus Six-Membered Ring Formation

Contact Info

Product

Resources

About

Applications and Limitations of the I₂-Mediated Carbamate Annulation for the Synthesis of Piperidines: Five- versus Six-Membered Ring Formation