72432-03-2

Basic information

• Product Name: Miglitol
• Synonyms: 1-(2-hydroxyethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol;GLYSET;N-(B-HYDROXYETHYL)-1-DEOXYNOJIRIMYCIN;MIGLITOL;1,5-dideoxy-1,5-[(2-hydroxyethyl)imino]-D-glucitol;Diastabol;Plumarol;Glyset, N-(b-Hydroxyethyl)-1-deoxynojirimycin,
• CAS NO: 72432-03-2
• Molecular Formula: C₈H₁₇NO₅
• Molecular Weight: 207.22
• EINECS: 276-661-6
• Product Categories: Antidiabetic;Diabetes;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Carbohydrates & Derivatives;AVELOX
• Mol File: 72432-03-2.mol

Chemical Properties

• Melting Point: 114°C
• Boiling Point: 453.7 °C at 760 mmHg
• Flash Point: 284.3 °C
• Appearance: white to light yellow crystal powder
• Density: 1.458 g/cm³
• Vapor Pressure: 3.87E-10mmHg at 25°C
• Refractive Index: 1.597
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in DMSO (up to 50 mg/ml with warming), or in Water (up to 60 mg/ml).
• PKA: 5.9(at 25℃)
• Water Solubility: Soluble
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 1 month.
• Merck: 14,6187
• CAS DataBase Reference: Miglitol(CAS DataBase Reference)
• NIST Chemistry Reference: Miglitol(72432-03-2)
• EPA Substance Registry System: Miglitol(72432-03-2)

Safety Data

• WGK Germany: 3
• RTECS: TN4350170
• Hazardous Substances Data: 72432-03-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Miglitol is used as an inhibitor of alpha-glucosidases for the treatment of non-insulin dependent diabetes (NIDDM). It helps to delay the absorption of complex carbohydrates, reducing postprandial glucose excursions and providing an auxiliary treatment for managing blood sugar levels.
Used in Antidiabetic Drug Development:
Miglitol is used as a potent α-glucosidase inhibitor, serving as a new antidiabetic drug. Its ability to delay carbohydrate absorption makes it a valuable addition to the treatment options for diabetes management.
Used in Antibacterial Applications:
Miglitol is also used in antibacterial applications, although the specific reasons and mechanisms for its use in this context are not detailed in the provided materials.

Indications

Miglitol [Glyset] is the second alpha-glucosidase inhibitor approved in the United States. Like acarbose, miglitol delays conversion of oligosaccharides and complex carbohydrates to glucose and other monosaccharides, and thereby reduces the postprandial rise in blood glucose. In clinical trials, the drug was especially effective among Latinos and African Americans. Hypoglycemia does not occur with miglitol monotherapy, but may occur if the drug is combined with insulin or a sulfonylurea. Like acarbose, miglitol causes flatulence, abdominal discomfort, and other GI effects. In contrast to acarbose, miglitol has not been associated with liver dysfunction. As with acarbose therapy, oral sucrose cannot be used to treat hypoglycemia. Rather, oral glucose must be given. Miglitol is available in 25-, 50-, and 100-mg tablets. The initial dosage is 25 mg 3 times daily before meals. The maintenance dosage is 50 or 100 mg 3 times a day.

Production Methods

Miglitol requires 1-deoxynojirimycin as a precursor which can be obtained via three different routes: extraction from plants such as the mulberry tree, fermentation using various bacterial strains, and a complete chemical synthesis. Industrially feasible production of miglitol was, however, restricted by expensive purification steps or low yields. Hence, a new approach was adopted in which a combination of biochemical and chemical synthesis was employed (Schedel, 2000). In this approach, D-glucose is converted to 1-amino-D-sorbitol by reduction with suitable amines and hydrogen, with nickel as catalyst, and then further reaction of products with appropriate acid esters (Kinast and Schedel, 1979). The oxidation of 1-amino-D-sorbitol to 6-amino-L-sorbose is then carried out in a fermenter using Gluconobacter oxydans grown at temperatures between 20 and 45 C, preferably at roomtemperature and maintaining thepHbetween 2.0 and 9.0. At this pH, 6-amino-L-sorbose is present in the medium as piperidinose, which is reduced to 1-desoxy-nojirimycin in the presence of inert solvents and by choosing the appropriate pH. After this, miglitol is obtained by first centrifuging the biomass followed by clarification using active charcoal. Next, separation of catalyst, evaporation of solvents, and isolation of any remaining salts in the medium is carried out (Kinast and Schedel, 1979). An important modification necessary in this process is the addition of protection groups before feeding 1-amino-D-sorbitol to the G. oxydans cultures and their subsequent removal before the ring-closure reaction. This is necessary since1-amino-D-sorbitol is readily oxidized by G. oxydans strains to form 3-hydroxy-2-hydroxymethyl-pyridine at near-neutral pH as a result of spontaneous ring closure (Schedel, 2000).

Manufacturing Process

50 g (0.23 mole) of 6-amino-6-desoxy-L-sorbose hydrochloride were dissolved in 500 ml of distilled water, and the solution was added in the course of onehour to a solution of 11.2 g of dimethylaminoborane in 500 ml of distilledwater, whilst stirring at a temperature of 50°C. The mixture was stirred forone hour at room temperature and one hour at 50°C, 5 ml of triethylaminewere added to it, and it was then poured over a column containing 800 ml ofstrongly basic ion exchanger ("Lewatit" MP 500 OH--form). The exchangerwas washed with distilled water, and the runnings collected were concentratedto a syrup on a rotary evaporator. The concentrated syrup was crystallised at50°C on addition of a large amount of ethanol. The suspension of crystals wascooled and filtered off under suction, and the crystalline product was dried ina vacuum drying cabinet. Yield: 30 g, 80% of theory. MP: 192°-193°C.25 g (0.115 mole) 1,5-didesoxy-1,5-imino-D-glucitol of 6-amino-6-desoxy-L-sorbose hydrochloride were dissolved in 200 ml of distilled water, and thesolution was added at 5°C to a mixture of 4.8 g of NaBH4, 250 ml ofethanol/water 1:1 and 16.2 ml of triethylamine, whilst stirring. The mixturewas further stirred for one hour at room temperature and one hour at 50°C.,and the reaction mixture was poured over a column containing 400 ml ofstrongly basic ion exchanger ("Lewatit" MP 500 OH-form). The exchanger waswashed with distilled water, and the eluate collected was concentrated to asyrup in a rotary evaporator. Th syrup was taken up with 200 ml of distilledwater, and the mixture was poured over a column containing 400 ml of acidion exchanger ("Lewatit" S 100 H+-form). The column was rinsed withdistilled water, and the product was eluted with 10% strength ammonia water.The runnings, rendered alkaline with ammonia, were collected and wereconcentrated to a syrup in a rotary evaporator. The syrup was crystallized,whilst warm, with a large amount of ethanol, and the suspension of crystalswas cooled and is filtered off under suction, and the crystalline product wasdried in a vacuum drying cabinet. Yield of 1,5-dideoxy-1,5-((2-hydroxyethyl)imino)-D-glucitol 14 g, 74% of theory. MP: 192°-193°C.

Therapeutic Function

Glucosidase inhibitor

Mechanism of action

The mechanism of action of miglitol is very similar to that of acarbose; it has strong binding affinity to digestive enzymes and, as a result, prevents these enzymes from binding to complex carbohydrates thereby delaying glucose absorption and resulting in reduction in postprandial plasma levels. The difference to note is that miglitol is a competitive inhibitor of digestive enzymes as a substitute for glucose, whereas acarbose functions as a substitute for the starch and oligosaccharides. Miglitol shows inhibitory action toward almost all the digestive enzymes present in the brush border of small intestine with the following ranking order: sucrase > glucoamylase > isomaltase > lactase > trehalase, and some inhibitory activity toward a-amylase (Lembcke et al., 1985; Scott and Spencer, 2000). Both acarbose and voglibose are not absorbed in the upper section of upper intestine. Miglitol, however, is almost completely absorbed in the small intestine (Scott and Spencer, 2000; Tan, 1997). The absorption of miglitol is dose dependent, with 25 mg of miglitol rapidly and completely absorbed. However, higher doses of up to 100 mg do not get fully absorbed, and 95% of miglitol is excreted out of the system via urine and feces almost unchanged. The amount excreted depends upon the systemic absorption, and therefore on the dose administered. With the lowest dose of 25 mg, almost 95% excretion is achieved, but with higher dosages this amount drops. The half-life of miglitol in healthy volunteers is 2–3 h for a less potent dose of 50 mg (Ahr et al., 1997; Campbell et al., 2000; Scott and Spencer, 2000).

Clinical Use

One of the widely used a-glucosidase inhibitors for treatment of Type II diabetes is miglitol (C8H17NO5; IUPAC name (2R,3R,4R,5S)-1-(2-hydroxyethyl)- 2-(hydroxymethyl)piperidine-3,4,5-triol; molecular weight 207.2). Miglitol is a second-generation a-glucosidase inhibitor derived from 1-deoxynojirimycin, which is yet another a-glucosidase inhibitor and is structurally similar to glucose (Tan, 1997). It is a white to pale yellow powder and is soluble in water (Campbell et al., 2000). Miglitol was approved by the U.S. Food and Drug Administration (FDA) in 1996 as an additional therapy to diet alone therapy or diet plus sulfonylurea therapy in patients with Type II diabetes. Miglitol’s story begins with the successful attempts for identifying new compounds with inhibitory properties, which initially resulted in the discovery of nojirimycin, deoxynojirimycin, and their derivatives from various Bacillus and Streptomyces strains (Schmidt et al., 1979). During initial attempts, 1-deoxynojirimycin was successfully obtained (Schmidt et al., 1979); however, its N-hydroxyethyl analog (miglitol) later proved to possess better inhibitory activities. It is currently being manufactured by Bayer AG under the trade name of Glysetò in USA and as Diastabolò in Europe. Miglitol is considered to be a good choice for the therapy of patients who have the relative risk of developing hypoglycemia, weight gain, or lactic acidosis (Campbell et al., 2000). It is observed to have the same efficacy as acarbose at lesser dosages (50 and 100 mg tid). Miglitol therapy provides better reduction on fasting and postprandial plasma glucose levels in patients in comparison with sulfonylureas (Scott and Spencer, 2000), whereas voglibose, another a-glucosidase inhibitor, could achieve reduction only for postprandial glucose levels.

Synthesis

1-Deoxynojirimycin and its N-substituted analog N-hydroxyethyl-1- deoxynojirimycin (miglitol) are strong inhibitors of α-glucosidases and are used for the treatment of non-insulin-dependent diabetes (Campbell et al., 2000). The industrial production of these compounds follows a combined biotechnological- chemical synthesis, whereby G. oxydans plays a key-role in the oxidation of 1-aminosorbitol derivatives. As Gluconobacter cannot grow on aminopolyols, whole resting cells (grown on sorbitol) have to be used for this biotransformation process. SYNTHESIS OF 1-DEOXYNOJIRIMYCIN AND MIGLITOL

References

1) Lee et al. (2002), The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics; Diabetes Obes. Metab., 4 329 2) Nomura et al. (2011), Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin level in patients with type 2 diabetes mellitus; Int. J. Gen. Med., 4 539 3) Yokoyama et al. (2007), Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus; Metabolism, 56 1458

InChI:InChI=1/C8H17NO5/c10-2-1-9-3-6(12)8(14)7(13)5(9)4-11/h5-8,10-14H,1-4H2/t5?,6-,7?,8-/m1/s1

Synthetic route

miglitol (72432-03-2) + benzaldehyde (100-52-7) → C15H21NO5 (1194233-02-7)

Conditions	Yield
With zinc(II) chloride at 50℃; for 48h;	90%

Upstream product

• 1203659-54-4 N-(2-benzyloxyethyl)-1-deoxynojirimycin 
• 1221793-46-9 N-(2-hydroxy-ethyl)-2,3,4,6-tetra-O-benzyl-1-deoxynojirimycin 
• 1316108-84-5 (2S,3R,4R,5R)-2,3,4,6-tetrakis(benzyloxy)-5-hydroxyhexyl pivalate 
• 4291-69-4 2,3,4,6-Tetra-O-benzyl-D-glucopyranose 
• 78136-16-0 2,3,4,6-tetra-O-benzyl-D-glucitol 
• 78136-16-0 (2S,3R,4R,5S)-2,3,4,6-tetrakis(benzyloxy)hexane-1,5-diol 
• 157363-84-3 1,2:5,6-dianhydro-3,4-di-O-benzyl-L-iditol 
• 172147-86-3 Methanesulfonic acid (1R,2S,3S,4R)-2,3-bis-benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-1-(tert-butyl-dimethyl-silanyloxymethyl)-4-methanesulfonyloxy-pentyl ester 
• 172147-87-4 (2R,3R,4R,5R)-3,4-Bis-benzyloxy-1,6-bis-(tert-butyl-dimethyl-silanyloxy)-hexane-2,5-diol 
• 36199-02-7 3,4-di-O-benzyl-D-mannitol 
• 139189-61-0 2,3,4,6-tetra-O-benzyl-D-xylo-hex-5-ulosononitrile 
• 19130-96-2 1,5-dideoxy-1,5-imino-D-glucitol 
• 60656-87-3 benzyloxyacetoaldehyde 
• 308273-88-3 [(2S,3R,4R,5S)-3,4,5-Tris-benzyloxy-1-(2-benzyloxy-ethyl)-piperidin-2-yl]-methanol 

Downstream Products

• 1194233-02-7 (R)-4,6-O-benzylidene-N-(2-hydroxyethyl)-1,5-dideoxy-1,5-imino-D-glucitol 
• 1194233-03-8 (R)-4,6-O-benzylidene-N-(2-triphenylmethyloxyethyl)-1,5-dideoxy-1,5-imino-D-glucitol 
• 1258076-55-9 2,3-di-O-acetyl-4,6-O-benzylidene-1,5-dideoxy-N-(2-triphenylmethyloxyethyl)-1,5-imino-D-glucitol 
• 1258076-57-1 2,3-di-O-acetyl-4,6-O-benzylidene-1,5-dideoxy-N-(2-hydroxyethyl)-1,5-imino-D-glucitol 
• 1258076-58-2 2,3-di-O-acetyl-4,6-O-benzylidene-1,5-dideoxy-N-(2-fluoroethyl)-1,5-imino-D-glucitol 
• 1258076-60-6 2,3-di-O-acetyl-N-(2-acetyloxyethyl)-4,6-O-benzylidene-1,5-dideoxy-1,5-imino-D-glucitol 
• 1258076-61-7 2,3-di-O-acetyl-6-O-benzyl-1,5-dideoxy-N-(2-acetyloxyethyl)-1,5-imino-D-glucitol 
• 1258076-62-8 2,3,4-tri-O-acetyl-N-(2-acetyloxyethyl)-6-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol 
• 1194233-02-7 C₁₅H₂₁NO₅ 

Relevant articles and documents

Preparation method of miglitol

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of miglitol. The method comprises the following steps: (1) adding Pd/C and SM-1 into a reaction solvent in a high-pressure reaction kettle, adding an acid, conducting stirring, controlling the temperature and pressure, carrying out hydrogenation reaction, cooling the reaction solution to room temperature after the reaction is finished, conducting filtering, and carrying out reduced pressure concentration until the reaction solution is dry to obtain a solid; and (2) adding an organic solvent into the obtained solid for dissolution, adding a crystallization solvent for crystallization, completely conducting crystallizing, conducting filtering, and carrying out vacuum drying toobtain a target compound miglitol. Compared with the prior art, the invention provides a simple, convenient and efficient method for preparing miglitol, and the whole synthesis method has the advantages of short route, simple operation steps, high reaction yield, high product purity, mild reaction conditions, effective shortening of the production period, and suitableness for industrial scale-upproduction.

Iminosugars: Effects of stereochemistry, ring size, and n-substituents on glucosidase activities

N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 μM and 138 μM, respectively, using DNJ as reference (IC50 134 μM). On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 μM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 μM). Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 μM) of the corresponding D-gluco-piperidine miglustat drug (40a). Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 μM.

Preparation method for miglitol

The invention discloses a preparation method for miglitol. The method comprises the following steps: selecting 6-deoxy-6-hydroxyethylamino-alpha-L-sorbose as a raw material, adding an alcohol solvent,performing a catalytic hydrogenation reaction under a certain pressure condition in the presence of a hydrogen gas, then performing pressure filtration, performing concentration, performing crystallization, performing vacuum filtration, performing washing, and performing vacuum drying to obtain the miglitol crystal. According to the invention, the reaction time is 7-8h, the temperature is 20-30 DEG C, the yield is greater than 90%, and the purity is greater than 99% (HPLC detection); and the reagents used by the method are green, environmentally friendly, pollution-free, economical and practical, the reaction yield is high, and the method is simple and convenient for operation, and suitable for industrialized mass production.

One pot oxidative dehydration - oxidation of polyhydroxyhexanal oxime to polyhydroxy oxohexanenitrile: A versatile methodology for the facile access of azasugar alkaloids

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).

Facile and stereo-controlled synthesis of 2-deoxynojirimycin, Miglustat and Miglitol

A novel and facile synthesis of a series of the biologically significant iminosugar derivatives including 2-deoxynojirimycin, Miglustat and Miglitol is reported. The synthesis features a strategic double inversion mechanism for securing the desired stereochemistry at C5 position of such glucose-type carbohydrate mimetics, representing a practical and remarkable improvement on the previously reported method that suffers from the loss of the stereo-control during the reaction process. Crown Copyright

Dual-action lipophilic iminosugar improves glycemic control in obese rodents by reduction of visceral glycosphingolipids and buffering of carbohydrate assimilation

The lipophilic iminosugar N-[5-(adamantan-1-ylmethoxy)pentyl]-1- deoxynojirimycin (2, AMP-DNM) potently controls hyperglycemia in obese rodent models of insulin resistance. The reduction of visceral glycosphingolipids by 2 is thought to underlie its beneficial action. It cannot, however, be excluded that concomitant inhibition of intestinal glycosidases and associated buffering of carbohydrate assimilation add to this. To firmly establish the mode of action of 2, we developed a panel of lipophilic iminosugars varying in configuration at C-4/C-5 and N-substitution of the iminosugar. From these we identified the L-ido derivative of 2, L-ido-AMP-DNM (4), as a selective inhibitor of glycosphingolipid synthesis. Compound 4 lowered visceral glycosphingolipids in ob/ob mice and ZDF rats on a par with 2. In contrast to 2, 4 did not inhibit sucrase activity or sucrose assimilation. Treatment with 4 was significantly less effective in reducing blood glucose and HbA1c. We conclude that the combination of reduction of glycosphingolipids in tissue and buffering of carbohydrate assimilation by 2 produces a superior glucose homeostasis.

D-fructose-6-phosphate aldolase in organic synthesis: Cascade chemical-enzymatic preparation of sugar-relafed polyhydroxylated compounds

Novel aldol addition reactions of dihydroxyacetone (DHA) and hydroxyacetone (HA) to a variety of aldehydes catalyzed by D-fructose-6-phosphate aldolase (FSA) are presented. In a chemical-enzymatic cascade reaction approach, 1-deoxynojirimycin and 1-deoxymannojirimycin were synthesized starting from (R)- and (S)-3-(N-Cbz-amino)-2-hydroxypropanal, respectively. Furthermore, 1,4-dideoxy1,4-imino-D-arabinitol and 1,4,5-trideoxy-1,4-imino-D-arabinitol were prepared from N-Cbz-glycinal, 1 -Deoxy-D-xylulose was also synthesized by using HA as the donor and either 2-benzyloxyethanal or 2-hydroxyethanal as acceptors. In both cases the enzymatic aldol addition reaction was fully stereoselective, but with 2-hydroxyethanal 17% of the epimeric product at C2, 1-deoxy-D-erythro-2-pentulose, was observed due to enolization/epimerization during the isolation steps. It was also observed that D-(-)-threose is a good acceptor substrate for FSA, opening new synthetic possibilities for the preparation of important novel complex carbohydrate-related compounds from aldoses. To illustrate this, 1-deoxy-D-ido-hept-2-ulose was obtained stereoselectively by the addition of HA to D-(-)-threose, catalyzed by FSA. It was found that the reaction performance depended strongly on the donor substrate, HA being the one that gave the best conversions to the aldol adduct. The examples presented in this work show the valuable synthetic potential of FSA for the construction of chiral complex polyhydroxylated sugar-type structures.

USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS

The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula

New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii

Chromatographic separation of the pod extract of Angylocalyx pynaertii resulted in the isolation of 13 sugar-mimic alkaloids (1-13). The structures of the new alkaloids were elucidated by spectroscopic methods as the 6-O-β-D-glucoside (10) and N-hydroxyethyl derivative (11) of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) (1), 1,6-dideoxynojirimycin (12), and 1,3,4-trideoxynojirimycin (13). 2,5-Imino-1,2,5-trideoxy-L-glucitol (7), 2,5-dideoxy-2,5-imino-D-fucitol (8), and β-homofuconojifimycin (9), isolated from the pods as well as the bark, were very specific inhibitors of α-L-fucosidase with no significant inhibitory activity toward other glycosidases. In this work, 1,4-dideoxy-1,4-imino-D-ribitol (6) was found to be a better inhibitor of lysosomal β-mannosidase than 2,5-imino-1,2,5-trideoxy-D-mannitol (2). N-Hydroxyethyl-1-deoxynojirimycin (miglitol), which is commercially available for the treatment of diabetes, retained its inhibitory potential toward rat intestinal maltase and sucrase, whereas 11 and the synthetic N-hydroxyethyl derivative of 2,5-dideoxy-2,5-imino-D-mannitol markedly lowered or abolished their inhibition toward all enzymes tested.

Lipophilic prodrugs of 1-deoxynojirimycin derivatives

We report a new synthesis of Miglitol, and its conversion to a lipophilic prodrug. The same procedure permits the preparation of a prodrug of 1-desoxynojirimycin and probably of other 1-deoxynojirimycin derivatives. (C) 2000 Elsevier Science Ltd.