62362-40-7

Upstream product

• 138319-95-6 (4S,5R)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-5-((4R,5S)-5-formyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 123149-59-7 5-amino-5-deoxy-D-mannopyranose hydrogensulfite 
• 78698-43-8 5-amino-5-deoxy-L-altropyranose hydrogensulfite adduct 
• 14635-94-0 2-amino-2-deoxy-D-mannitol 
• 91364-19-1 5-amino-1-O-benzyl-5-deoxy-2,3-O-isopropylidene-α-D-mannofuranose 
• 81703-56-2 5-amino-5-deoxy-D-glucose-1-sulfonic acid 

Downstream Products

• 14904-83-7 nojirimycin-δ-lactam 

Relevant academic research and scientific papers

Medium-chain dehydrogenases with new specificity: Amino mannitol dehydrogenases on the azasugar biosynthetic pathway

Azasugar biosynthesis involves a key dehydrogenase that oxidizes 2-amino-2-deoxy-D-mannitol to the 6-oxo compound. The genes encoding homologous NAD-dependent dehydrogenases from Bacillus amyloliquefaciens FZB42, B. atrophaeus 1942, and Paenibacillus polymyxa SC2 were codon-optimized and expressed in BL21(DE3) Escherichia coli. Relative to the two Bacillus enzymes, the enzyme from P. polymyxa proved to have superior catalytic properties with a Vmax of 0.095 ± 0.002 μmol/min/mg, 59-fold higher than the B. amyloliquefaciens enzyme. The preferred substrate is 2-amino-2-deoxy-D- mannitol, though mannitol is accepted as a poor substrate at 3% of the relative rate. Simple amino alcohols were also accepted as substrates at lower rates. Sequence alignment suggested D283 was involved in the enzyme's specificity for aminopolyols. Point mutant D283N lost its amino specificity, accepting mannitol at 45% the rate observed for 2-amino-2-deoxy-D-mannitol. These results provide the first characterization of this class of zinc-dependent medium chain dehydrogenases that utilize aminopolyol substrates.

Microbial oxidation of aromatics in enantiocontrolled synthesis. 2.1 rational design of aza sugars (endo-nitrogenous). Total synthesis of (+)-kifunensine, mannojirimycin, and other glycosidase inhibitors

A general method of synthesis for lactones and lactams related to carbohydrates has been developed that relies on the biocatalytic generation of 1-chloro-2,3-dihydroxycyclohexa-4,6-diene (1), obtained in excellent yield by fermentation of chlorobenzene with Pseudomonasputida 39D, followed by further functionalization to nitrogen-substituted cyclitols. These amino or azido cyclitols of type 15 are then subjected to controlled ozonolysis, which yields either lactones such as 27 or lactams containing five-membered (28) or six-membered (20 and 23) rings. Such compounds are useful intermediates for the preparation of aza sugars. Mannojirimycin (8a) has been synthesized in seven steps from chlorobenzene. Kifunensine (7) has been prepared in 11 steps from chlorobenzene following an intersection with Hashimoto's procedure. Full experimental and spectral details are provided for all compounds. The potential of this general method and implications of the disclosed design features in the field of amino sugar and aza sugar synthesis are indicated.

Amidine, amidrazone, and amidoxime derivatives of monosaccharide aldonolactams: Synthesis and evaluation as glycosidase inhibitors

The synthesis of amidine, amidrazone, and amidoxime derivatives of D-glucono, D-mannono, and D-galactonolactams, which are potent glycosidase inhibitors, is described. With their sugar-like structures and resonance-stabilized, partially positively charged anomeric carbons, these monosaccharide analogs mimic key conformational and electrostatic features of the corresponding glycopyranosyl cations. In the D-gluco series, all three derivatives are potent inhibitors of sweet almond β-glucosidase. Levels of inhibition remain nearly constant despite a 105 change in basicity, indicating that conformational flattening of the hydrolysis intermediate is more important for transition-state binding by the enzyme than charge development. The same D-gluco derivatives also interact with mannose- and galactose-processing enzymes. Considerably weaker inhibition is observed with 1β-amino-1-deoxynojirimycin, which embodies similar endocyclic and exocyclic nitrogens in an undistorted chair conformation. In the D-manno series, the amidrazone and amidoxime are potent inhibitors of jackbean α-mannosidase, mung bean α-mannosidase, fungal β-mannosidase, Golgi α-mannosidase I, α-mannosidase II, and soluble (or endoplasmic reticulum) α-mannosidase. The mannoamidrazone also inhibits Golgi α-mannosidase I and the endoplasmic reticulum mannosidase in vivo. In the D-galacto series, significant inhibition of almond β-glucosidase, bovine liver β-galactosidase, and green coffee bean α-galactosidase is observed, but little or no inhibition of amyloglucosidase.

Stereocontrolled Total Synthesis of Galactostasin from Serine

An efficient stereoselective total synthesis of (-)-galactostasin (-)-1 from N-tert-butoxycarbonyl-2,3-isopropylidene L-serine methyl ester (21percent overall yield) is described via thiazole intermediates serving as protected aldehydes; the parallel synt

Synthesis of 5-amino-5-deoxy-D-galactopyranose and 1,5-dideoxy-1,5-imino-D-galactitol, and their inhibition of alpha- and beta-D-galactosidases.

A 12-step route is presented starting from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose for the preparation of the title compounds and their L-altro analogues. Their synthesis is based on the reduction with Raney nickel of a protected 5-hydroxyimino derivative of L-arabino-hexofuranos-5-ulose, with the following improvements for the preparation of a D-galactofuranose derivative: oxidation at C-3 with pyridinium dichromate-acetic anhydride, stereospecific reduction of a 3-O-acetyl-hex-3-enofuranose intermediate to the D-gulo derivative, and inversion at C-3 of its 3-tosylate with tetrabutylammonium acetate in chlorobenzene. alpha-D-Galactosidase from coffee beans and from Escherichia coli and beta-D-galactosidase from E. coli and Aspergillus wentii were inhibited with Ki values that ranged from 0.0007 to 8.2 microM. Formation of the enzyme-inhibitor complexes with the D-galactose analogue was on the time-scale of minutes, whereas the D-galactitol analogue showed a slow approach to the inhibition only with alpha-D-galactosidase from coffee beans and beta-D-galactosidase from A. wentii. N-Alkylation of the D-galactitol analogue was detrimental to the inhibition except for beta-D-galactosidase from E. coli and beta-D-glucosidase from almonds, but, even with these enzymes, the observed affinity enhancements were 10(2) to 10(3)-times smaller than those of N-alkylated D-galactosylamine and D-glucosylamine.

SYNTHESIS OF 5-AMINO-5-DEOXY-D-MANNOPYRANOSE AND 1,5-DIDEOXY-1,5-IMINO-D-MANNITOL, AND INHIBITION OF α- AND β-D-MANNOSIDASES

The title compounds and the corresponding L-gulo derivatives were synthesised in 6 steps from benzyl 2,3:5,6-di-O-isopropylidene-α-D-mannofuranoside.The Ki values, determined from inhibition studies with α-D-mannosidases from jack beans, almonds, and calf liver, and β-D-mannosidase from Aspergillus wentii, ranged from 70 to 400 μM for the mannitol derivative and from 1.2 to 20 μM for 5-amino-5-deoxy-D-mannopyranose, i.e., inhibition is E2-E4-fold stronger than with D-mannose.Marked enhancement of inhibition with increasing pH is ascribed to the ionisation of a carboxyl group at the active site, forming an ion pair with the protonated inhibitor.The inhibition equilibrium between the jack-bean enzyme and the mannose derivative was approached slowly with kapp 2.0E5 M-1.min-1.The mannose-derived inhibitor was also inhibitory against β-D-glucosidases from almonds and Asp. wentii, with Ki values only 20-150-times larger than those for the inhibition of these enzymes by 5-amino-5-deoxy-D-glucopyranose.This moderate discrimination in binding of D-gluco and D-manno derivatives is in marked contrast to the high specificity shown by the glucosidase in catalysing the hydrolysis of mannosidases.A similar low specificity with respect to binding, combined with highly specific catalysis, was also seen with the mannosidases acting on inhibitors and substrates with the D-gluco configuration.