19130-96-2 Usage
Chemical Name
(2R,3R,4R,5S)-2-Hydroxymethyl-piperidine-3,4,5-triol
Alkaloids
1-deoxynojirimycin? is referred DNJ for short? , it is an alkaloid extracted from the bark of mulberry leaves and roots, but it also exists in other plants and microorganisms. This product is an effective α-glucosidase inhibitor, it has significant hypoglycemic effect. After 1-deoxynojirimycin goes into the human body, it can inhibit sucrose, maltase, α-glucosidase enzyme, α-amylase decomposing? starch, sugar in the human body , thereby it can block the body's absorption of sugar, inhibiting blood sugar rising to achieve the effect of prevention and treatment of diabetes, the use of it does not cause changes in diet . In addition, DNJ can inhibit glucose modification process of HIV tunica glycoprotein , at the same time, the accumulation of immature glycoproteins may inhibit cell fusion, viral and host cell receptor can combine,which causes? syncytia formation to inhibit the replication of? MoLV ,then the virus activity is inhibited.
Nojirimycin is first discovered from Streptomyces, and natural DNJ is first isolated from the bark of mulberry root. In plants, from mulberry, dayflower, hyacinth and Adenophora plants, DNJ has been isolated and identified ,? DNJ has the highest content in the mulberry and because of mulberry varieties, medicinal parts, seasonal climate, geography, soil, leaf position, different developmental stages? and other factors , there is a big difference. In a microorganism, from a variety of Streptomyces and Bacillus,DNJ is isolated ,it is also found that two kinds of endophytes separated from Mulberry including Stenotrophomonas oligotrophic Pseudomonas and Micrococcus can produce DNJ,fermentation conditions of a variety of? microbial production of DNJ are studied. In insects, in addition to silkworm rich in DNJ , single or oligophagous insects with eating mulberry leaves habit including wild silkworm, mulberry geometrid, Diaphania pyloalis Walker , mulberry white capterpillar are also rich in DNJ , DNJ in insects bodies are from the food , content of DNJ in Bombyx bodies is different due to the different varieties of silkworm, developmental stages, tissues and organs as well as feed and other factors, with the silkworm age of progress ,there is the existence of cyclical changes in absorption and accumulation and excretion of DNJ. Now DNJ biosynthetic pathways in Streptomyces, Bacillus and Commelina bodies are explored and it is found that? synthesis of DNJ has different mechanisms in different species . In addition, three main synthesis methods of 1-deoxynojirimycin are proven , some of the synthetic derivatives of DNJ have been used clinically.
Recent studies show that the active ingredient of mulberry DNJ (l-deoxynojirimycin), only exists in mulberry leaves , by blocking the α-glucosidase enzymes to hinder sugar? becoming to glucose, mulberry leaf extract can inhibit intestinal glucose absorption. This can suppress the blood sugar level and blood pressure rising , and it can have good inhibitory effect on variability of imidazopyridine, benzopyrene and other carcinogenic substances,it has anti-cancer effect, at the same time ,mulberry leaf extract can reduce cholesterol, and improve liver function and eliminate constipation and so on.
Description
Deoxynojirimycin (19130-96-2) inhibits α-glucosidase I and II.1,2 Inhibits human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step.3 May be used to produce an affinity ligand for purifying glucosidase 1.4 Deoxynojirimycin was used to inhibit ER glucosidases I and II allowing for the discovery of a second mechanism for deglucosylation of N-linked oligosaccharides in PhaR1.7, a mouse lymphoma cell line.5
Chemical Properties
White Crystalline Solid
Uses
Different sources of media describe the Uses of 19130-96-2 differently. You can refer to the following data:
1. Deoxynojirimycin inhibits mammalian glucosidase 1. As well, it inhibits intestinal and lysosmal alpha-glucosidases, beta-glucosidase from sweet almonds, pancreatic alpha-amylase and amyloglucosidase.
2. An inhibitor of α-glucosidase I and II
3. An alpha-glucosidase inhibitor. Interferes with normal processing of N-linked glycoproteins.(+)-1-Deoxynojirimycin acts as an inhibitor of alfa-glucosidase I and II and maltase-glucoamylase. It also inhibits mammalian glucosidase, intestinal and lysosmal, beta-glucosidase from sweet almonds, pancreatic alfa-amylase and amyloglucosidase. Further, it serves as a enzyme enhancer for the treatment of Fabry and Pompe disease.
Definition
ChEBI: An optically active form of 2-(hydroxymethyl)piperidine-3,4,5-triol having 2R,3R,4R,5S-configuration.
Biological Activity
Inhibitor of glucosidase I (K i = 2.1 mM) and II (K i = 7 mM).
References
1) Fuhrmann et al. (1985), Inhibitors of oligosaccharide processing; Biochim. Biophys, Acta, 825 95
2) Hughs and Rudge (1994), Deoxynojirimycin: synthesis and biological activity; Nat. Prod. Rep., 11 135
3) Papandreou et al. (2002), The alpha-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step; Mol. Pharmacol., 61 186
4) Hettkamp et al. (1984), Purification by affinity chromatography of glucosidase I, an endoplasmic reticulum hydrolase involved in the processing of asparagine-linked oligosaccharides; Eur. J. Biochem., 142 85
5) Suh et al. (1992), Identification of a novel mechanism for the removal of glucose residues from high mannose-type oligosaccharides; J. Biol. Chem., 267 21671
Check Digit Verification of cas no
The CAS Registry Mumber 19130-96-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,9,1,3 and 0 respectively; the second part has 2 digits, 9 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 19130-96:
(7*1)+(6*9)+(5*1)+(4*3)+(3*0)+(2*9)+(1*6)=102
102 % 10 = 2
So 19130-96-2 is a valid CAS Registry Number.
InChI:InChI=1/C6H13NO4/c8-2-3-5(10)6(11)4(9)1-7-3/h3-11H,1-2H2/t3?,4?,5-,6-/m1/s1
19130-96-2Relevant articles and documents
1,3-Oxazine as a chiral building block used in the total synthesis of (+)-1-deoxynojirimycin and (2R,5R)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine
Park, Seok-Hwi,Kim, Ji-Yeon,Kim, Jin-Seok,Jung, Changyoung,Song, Dong-Keun,Ham, Won-Hun
, p. 657 - 661 (2015)
Concise and stereocontrolled syntheses of (+)-1-deoxynojirimycin and (2R,5R)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine [(+)-DMDP] were achieved via a diastereomerically enriched oxazine intermediate. The key strategies include the use of 1,3-oxazine as a chiral building block and diastereoselective nucleophilic addition to an aldehyde. Starting from readily available (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate, (+)-1-deoxynojirimycin was synthesized in 11 steps and 26.2% overall yield while (+)-DMDP was synthesized in 11 steps and 27.1% overall yield, respectively.
A fluorescence study of isofagomine protonation in β-glucosidase
Lindb?ck, Emil,Laursen, Bo Wegge,Poulsen, Jens Christian Navarro,Kils?, Kristine,Pedersen, Christian Marcus,Bols, Mikael
, p. 6562 - 6566 (2015)
N-(10-Chloro-9-anthracenemethyl)isofagomine 5 and N-(10-chloro-9-anthracenemethyl)-1-deoxynojirimycin 6 were prepared, and their inhibition of almond β-glucosidase was measured. The isofagomine derivative 5 was found to be a potent inhibitor, while the 1-deoxynojirimycin derivative 6 displayed no inhibition at the concentrations investigated. Fluorescence spectroscopy of 5 with almond β-glucosidase at different pH values showed that the inhibitor nitrogen is not protonated when bound to the enzyme. Analysis of pH inhibition data confirmed that 5 binds as the amine to the enzyme's unprotonated dicarboxylate form. This is a radically different binding mode than has been observed with isofagomine and other iminosugars in the literature.
Design, synthesis, and activity evaluation of novel N-benzyl deoxynojirimycin derivatives for use as α-glucosidase inhibitors
Zeng, Fanxin,Yin, Zhongping,Chen, Jiguang,Nie, Xuliang,Lin, Ping,Lu, Tao,Wang, Meng,Peng, Dayong
, (2019/09/19)
To obtain α-glucosidase inhibitors with high activity, 19 NB-DNJDs (N-benzyldeoxynojirimycin derivatives) were designed and synthesized. The results indicated that the 19 NBDNJDs displayed different inhibitory activities towards α-glucosidase in vitro. Compound 18a (1- (4-hydroxy-3-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol) showed the highest activity, with an IC50 value of 0.207 ± 0.11 mM, followed by 18b (1-(3-bromo-4-hydroxy-5- methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol, IC50: 0.276 ± 0.13 mM). Both IC50 values of 18a and 18b were significantly lower than that of acarbose (IC50: 0.353 ± 0.09 mM). According to the structure-activity analysis, substitution of the benzyl and bromine groups on the benzene ring decreased the inhibition activity, while methoxy and hydroxyl group substitution increased the activity, especially with the hydroxyl group substitution. Molecular docking results showed that three hydrogen bonds were formed between compound 18a and amino acids in the active site of α- glucosidase. Additionally, an arene-arene interaction was also modelled between the phenyl ring of compound 18a and Arg 315. The three hydrogen bonds and the arene-arene interaction resulted in a low binding energy (-5.8 kcal/mol) and gave 18a a higher inhibition activity. Consequently, compound 18a is a promising candidate as a new α-glucosidase inhibitor for the treatment of type II diabetes.
Synthesis of 1-deoxynojirimycin: Exploration of optimised conditions for reductive amidation and separation of epimers
Iftikhar, Mehwish,Wang, Lin,Fang, Zhijie
, p. 460 - 464 (2017/08/18)
1-Deoxynojirimycin (DNJ), which has importance with respect to sugar processing enzymes, is a synthetic target for chemists. A key step in the synthesis of DNJ is the preparation of 2,3,4,6-tetra-O-benzyl-D-glucono-δ-lactam. By varying reaction parameters such as temperature, solvent and reducing reagent, improvements on previous methods are described. A novel approach for the synthesis of 2,3,4,6-tetra-O-benzyl-5-dehydro-5-deoxo-D-gluconamide has been developed by using PCC as an oxidising agent. Separation of epimers permitted DNJ to be obtained in 85% yield after reduction and hydrogenolysis steps.
Conformational Behaviour of Azasugars Based on Mannuronic Acid
van Rijssel, Erwin R.,Janssen, Antonius P. A.,Males, Alexandra,Davies, Gideon J.,van der Marel, Gijsbert A.,Overkleeft, Herman S.,Codée, Jeroen D. C.
, p. 1297 - 1304 (2017/07/07)
A set of mannuronic-acid-based iminosugars, consisting of the C-5-carboxylic acid, methyl ester and amide analogues of 1deoxymannorjirimicin (DMJ), was synthesised and their pH-dependent conformational behaviour was studied. Under acidic conditions the methyl ester and the carboxylic acid adopted an “inverted” 1C4 chair conformation as opposed to the “normal” 4C1 chair at basic pH. This conformational change is explained in terms of the stereoelectronic effects of the ring substituents and it parallels the behaviour of the mannuronic acid ester oxocarbenium ion. Because of this solution-phase behaviour, the mannuronic acid ester azasugar was examined as an inhibitor for a Caulobacter GH47 mannosidase that hydrolyses its substrates by way of a reaction itinerary that proceeds through a 3H4 transition state. No binding was observed for the mannuronic acid ester azasugar, but sub-atomic resolution data were obtained for the DMJ?CkGH47 complex, showing two conformations—3S1 and 1C4—for the DMJ inhibitor.
