DE2758025A1 - Tri:hydroxy-piperidine derivs. - useful as glucosidase inhibitors for treating diabetes etc. and as animal feed additives - Google Patents

Abstract

Peperidine derivs. of formula (I) are new: (R1 = H, branched, linear or cyclic, opt. unsatd., aliphatic hydrocarbyl, aryl or heterocyclyl, all opt. substd.; R2 = H, OH, OR', SH, SR', NH2, NHR', NR'R", NH2CH2, R'NHCH2, R'R"NCH2, COOH, COOR', HOCH2, R'CONHCH2, R'CONR"CH2, R'SO2NHCH2, R'SO2NR"CH2, R'NHCONHCH2, R'NHCSNHCH2, R'OCONHCH2, SO3H, CN, CONH2, CONHR' or CONR'R"; R3 can be as R1 but is pref H, CH3, CH2OH, CH2NH2, CH2NHR', CH2NR'R", R'CONH.CH2, R'CONR"CH2, HalCH2, R'OCH2, R'COOCH2, R'SO2OCH2, R'SO2NHCH2, R'NH.CONHCH2, R'NHCSNH.CH2, R'OCONHCH2, CN, COOH, COOR', CONH2, CONHR', R'SO2NR"CH2, CONR'R"; R' and R" are as for R1; when (i) R3 = CH2OH; R2 = H or OH; (ii) R3 = CH2NH2 and R2 = OH; and also (iii) when R3=H, R2=H, OH, SO3H, CN or CH2NH2, R1 cannot be H). (I) inhibit alpha-glucosidases, esp. disaccharidases, so are useful in treating pre-diabetes, gastritis, obstipation, caries, gastro-intestinal infections, meterorism, flatulence, hypertension, atherosclerosis and esp. adiposity, diabetes and hyperlipoproteinaemia. They are also useful as animal feed additives to improve the meat-fat distribution.

Description

New derivatives of 3,4,5-trihydroxvpireridin, method

for their preparation and their use The present invention relates to new derivatives of 3,4,5-trihydroxypiperidine, several processes for their Production and their use as pharmaceuticals, in particular as a means against Diabetes, hyperlipemia and obesity, as well as in animal nutrition to influence the meat / fat ratio in favor of the meat content.

The new derivatives can be represented by formula I, in which R, H or an optionally substituted, straight-chain, branched or cyclic saturated or unsaturated aliphatic hydrocarbon radical or a given aromatic or heterocyclic radical, if substituted, and R2 represents -H, -OH, -OR ', -SH, -SR', - NH2, -NHR ', NH2CH2-, NHR'-CH2-, NR'R "-CH2 -, -COOH, -COOR ', HO-CH2-, R'CO-NHCH2-, R'CO-NR" CH2-, R'SO2NHCH2-, R'SO2-NR "denotes CH2-, -SO3H, -CN, -CONH2, -CCNHR 'or -CONR"R' and -R3 can assume the meaning given for R1, but preferably for -H, -CH3, -CH2OH , -CH2-NH2, NER'-CH2-, DiR'R "-CH2-, R'CONH-CH2-, R'CO-NR" CH2-, Hal-CH2-, R'O-CH2-, R ' COCCH2-, R'SO20-CH2-, R'SO2NHCH2-, R'SO2-NR "CH2-, R'NH-CO-NE-CH2-, R'NH-CS-NH-CH2-, R'O- CO-NH-CH2-, -CN, -COOH, -COOR ", -CONH2, -CONHR ', -CONR'R", where R', R "can have the meanings given above for R, and where for the case 5 = -OH2 OH and R2 = H or OH R is an optionally substituted, straight-chain, branched or cyclic, saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical, ie R is not H; and in the case R3 = H and R2 = H, OH, SO3H, -CN and CH2-NH2 R, is an optionally substituted, straight-chain, branched or cyclic, saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical, ie that R is not H; and in the case R3 = -CH2-NH2 and R2 = OH, R is an optionally substituted, straight-chain, branched or cyclic, saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical, ie R is not H.

Preferably R ,, R ', R "denote an alkyl radical with 1 to 30 in particular 1 to 18 0 atoms, an alkenyl radical or alkynyl radical with 2 to 18 in particular 3 to 10 0 atoms, a mono-, b or tricyclic radical with 3 to 10 0 atoms, which can be saturated, singly or doubly unsaturated, an aryl radical with 6 or 10 carbon atoms, a heterocyclic radical with 3 to 8, in particular 3 to 6 ring members, which can contain 1, 2, 3 or 4 heteroatoms, in particular N, O, S and on which one Benzene ring or another heterocycle of the type mentioned can be condensed, where said radicals 1 to 5 in particular bear 1, 2 or 3 substituents can.

Examples of substituents for alkyl include: hydroxy, Alkoxy with preferably 1 to 4 carbon atoms, in particular methoxy and ethoxy; Acyloxy, where the acyl radical of aliphatic carboxylic acids with 1 to 7 0 atoms, aromaticz carboxylic acids, especially phenylcarboxylic acids, which are present in the phenyl radical -OH, -halogen, in particular F, C1, Br, C, -C4-alkyl, C1-C4-alkoxy, nitro and / or Amino can be substituted, heterocyclic carboxylic acids, which differ from 5- or Derive 6-membered heterocycles which contain 1 to 3 heteroatoms (N, O, S) and be substituted in the heterocyclic ring by C1-C4-alkyl, chlorine, bromine, amino can, is derived; Amino, monoalkylamino and dialkylamino with preferably 1 to 4 carbon atoms per alkyl radical, in particular monomethylamino, monoethylamino, Dimethylamino and diethylamino, monoacylamino, the acyl radical being aliphatic Carboxylic acids with 1 to 7 0 atoms, aromatic carboxylic acids, in particular phenylcarboxylic acids, those in the phenyl radical by -OH, -halogen, in particular F, C1, Br, C1-C4-alkyl, C, -C * -alkoxy, Nitro and / or amino can be substituted, heterocyclic Carboxylic acids, which are derived from 5- or 6-membered heterocycles containing 1 to 3 heteroatoms (N, O, S) and in the heterocyclic ring by C1-C4-alkyl, chlorine, bromine, amino may be substituted, is derived; Mercapto, alkylthio with preferably 1 up to 4 carbon atoms, in particular methylthio and ethylthio; Halogen, preferably Fluorine, chlorine and bromine; Alkylcarbonyl with preferably 1 to 4 carbon atoms in the alkyl radical; Carboxy, nitro, cyano, the aldehyde function, the sulfonic acid group; as well as heterocyclic residues of the type mentioned above, in particular also of sugars, very particularly heterocyclic radicals derived from hexose or pentoses which are directly connected to the alkyl radical via a ring atom or via an -O-, -S- or -NH bridge could be.

Examples of heterocyclic substituents of the alkyl radicals are: pnthalimido, Pyridyl, thienyl, furyl, isoxazolyl, thiazolyl, glucopyranosyl, ribofuranosyl, oxiranyl and the like

Furthermore, aromatic substituents are suitable as substituents of the alkyl radicals Radicals such as naphthyl and especially phenyl, one or more, preferably 1 to 3 identical or different substituents from the series -OH, -NH2, Ct-C4-alkyl-NH-, C1-C4-dialkyl-N-, C1-C4-alkoxy, NO2, -CN, -COOH, -COO-alkyl (Ci-C4), C1-C6-alkyl, Halogen, especially fluorine, chlorine or Erom, C1-C4-alkylthio, -SH, Ci -C4-alkylsulfonyl, -SO3H, -302-NH2, -SO2-NH-alkyl (C1-C4).

The alkyl radical can also have a mono-, bi- or tricyclic substituent with preferably 3 to 10 carbon atoms, which in turn is represented by hydroxy, Amino, halogen, in particular fluorine, chlorine, bromine, or -COOH can be substituted.

The alkyl radical preferably has substituents such as hydroxy and alkoxy 1 to 4 carbon atoms, mercapto, alkylthio with 1 to 4 carbon atoms, halogen, Nitro, amino, monoalkylamino with 1 to 4 carbon atoms and acylamino, where the acyl radical is derived from aliphatic carboxylic acids with 1 to 6 carbon atoms.

For the cyclic mono-, bi- or tricyclic radicals R1, R 'and R "are the substituents mentioned for the alkyl radicals.

The aryl radicals can be one or more, preferably 1 to 3, identical or carry different substituents.

The following are exemplified as substituents: alkyl with 1 to 10 C atoms, which in turn is substituted, for example, by chlorine, nitro or cyano can be; optionally substituted alkenyl radicals having 1 to 10 carbon atoms; Hydroxy, alkoxy with preferably 1 to 4 carbon atoms; Amino, monoalkyl and Dialkylamino with preferably 1 to 4 carbon atoms per alkyl radical; Mercapto, Alkylthio having preferably 1 to 4 carbon atoms; Carboxy, carbalkoxy with preferably 1 to 4 carbon atoms, the sulfonic acid group, alkylsulfonyl with preferably 1 to 4 carbon atoms, arylsulfonyl, preferably phenylsulfonyl; Aminosulfonyl, Alkylamino- and dialkylaminosulfonyl with 1 to 4 carbon atoms per alkyl group, preferably methyl and dimethylaminosulfonyl; Nitro, cyano or the aldehyde group; Alkylcarbonylamino preferably having 1 to 4 carbon atoms; Alkylcarbonyl with 1 to 4 carbon atoms, benzoyl, benzylcarbonyl and phenylethylcarbonyl, where the last-mentioned alkyl, phenyl, benzyl and phenylethyl radicals in turn can be substituted for example by chlorine, nitro or hydroxyl.

The heterocyclic radicals Rr are preferably of heteroparaffinic, heteroaromatic or heteroolefinic 5- or 6-membered rings with preferably 1 to 3 identical or different heteroatoms derived. Stand as heteroatoms Oxygen, sulfur or nitrogen. These ring systems can have further substituents such as, for example, hydroxyl, amino or C -C * -alkyl groups carry or can be attached to them Benzene nuclei or further preferably 6-membered heterocyclic rings of the above Kind of fused.

Particularly preferred heterocyclic radicals are derived, for example of furan, pyran, pyrrolidine, piperidine, pyrazole, imldazole, pyrimidine, pyridazine, Pyrazine, triazine, pyrrole, pyridine, benzimidazole, quinoline, isoquinoline or purine away.

In the compounds of the formula I, R2 is preferably -H, -OH, -SO3H, -CN, -CH2NH2, -CH2NH- (C1-C6-alkyl), or Ra very particularly preferably represents —H, —SO3H, —CN.

R3 preferably represents hydrogen, -CH2OH, -OH3, -CH2NH2, -CH2NH- (C1-C6-alkyl) or However, R3 very particularly preferably represents —CH2OH.

It has been found that the new compounds of the formula I are potent Inhibitors for α-glucosidases, especially for disaccharidases. Hence are the new compounds are valuable means of influencing a large number of metabolic processes and thus enrich the treasure trove of medicines.

Compared to the 2-hydroxymethyl-3,4,5-trihydroxypiperidine known from DT-OS 2 o56 602 the new compounds have advantageous therapeutic properties.

It has also been found that compounds of the formula I are obtained if one in compounds of the formula II or IIa in which R1 and R5 have the meaning given above, the isopropylidene or cyclohexylidene protective group is removed by careful acid hydrolysis, it may be useful to remove the compounds of the formula I in the form of adducts of sulfurous acid or hydrocyanic acid (R2 = SO3H or CN). The compounds of the formula I with R2 = OH are set free from the bisulfate dide products by treatment with B-sen, preferably alkaline earth metal hydroxides such as Ca (OH) 2 or Sr (OH) 2, but in particular Ba (OH) 2. By reaction with hydrogen donor reducing agents such as NaBH4, the compounds of the formula I with R2 = OH are obtained from the compounds of the formula I with R2 = H.

It has also been found that compounds of the formula I are obtained if one uses the compounds of the formula I with R2 = OH in a manner known per se Reacts hydrogen cyanide to compounds of the formula I with R2 = CN and optionally off these compounds by catalytic hydrogenation of the nitrile group with R2 = -CH2NH2 and the amino group, if appropriate, in a manner known per se to compounds where R2 = R'CONCH2-, R'CONR "CH2-, NHR'-Ch2-, NR'R" -CH2- or R "is SO2NHCH2-, acylated, alkylated or sulfonylated.

The compounds of the formula I in which R2 -OR ', -SH, -SR', -NH2, -NHR 'or -NR'R "can be obtained by using compounds of the formula l with R = -OH in a manner known per se with alcohols (R'OH), H2S mercaptans (R'SH), Ammonia or amines (H2NR ', HNR'R ").

The compounds of the formula I in which R2 is -COOH are obtained by hydrolyzing compounds of the formula I with R2 = -CN in a manner known per se.

The carboxylic acids obtained in this way can be used in a manner known per se Wise compounds of the formula I with R2 = -COOR 'by reaction with alcohols (R'OH), Compounds of the formula I with R2 = -CONHR 'or -CONR'R "or -CONH2 by aminolysis the ester obtained with NH3, R'NH2 or R'R "NH.

Compounds of the formula I with R2 = -OH can also be obtained when one compounds of the formula II in a reaction step A with trifluoroacetahydride to compounds of the formula III and then in reaction step B by acid hydrolysis the isopropylidene protective group is split off and then in step C in the neutral until alkaline reaction medium removed the trifluoroacetyl group of the compound IV.

The specified reaction sequence can be illustrated as follows: In the formulas, Rs stands for trifluoroacetyl and R5 for trifluoroacetyl or hydrogen.

This sequence of reactions can be carried out analogously to compounds of the formula IIa transferred.

It has also been found that compounds of the formula I with R2 = H are obtained when compounds of the formula V are obtained with carbonyl compounds of the formula VI in which R6 and R7 have either H or the meaning given for Rn or are members of an alicyclic or heterocyclic ring, in the presence of a hydrogen donor reducing agent.

Compounds of the formula I with R2 = H are also obtained if amides of the formula VII in which Rs is either H or has the meaning given for R1, or carbamates of the formula VIII - if appropriate, derivatives of these compounds provided with hydroxyl protective groups - reduced to amines with an amide reducing agent.

Another method of making compounds of the formula I with R2 = H consists in using compounds of the formula V with reactive alkylating agents of the formula IX Z - R1 IX, where R1 has the meaning given above for alkyl and Z is an easily leaving group commonly used for alkylating agents such as, for example Is halide or # 0-SO3H.

In addition, compounds of the formula I are obtained if, for example, in compounds of the formula I where R3 = —CH2OH, the —CH2OH group is selectively converted in a manner known per se Converted group and this either reductively in the -CH3 Grupne or reductively converted into an amino group via a -CH2-N3 group. Compounds of the formula I are also obtained if the amino group in compounds of the formula I with 3 = -CH2NH2 is derivatized in a manner known per se with alkyl halides, aldehydes or ketones in the presence of a hydrogen donor, carbonic acid or sulfonic acid chlorides, chlorocarbonic acid esters, isocyanates and mustard oils .

Compounds of the formula I in which R1 is an acylamino, Substituted sulfonylamino, alkoxycarbonylamino, ureido or a thioureido group is an aliphatic or aromatic radical, is obtained starting from compounds of formula I, in which R1 is an aliphatic substituted by an amino group or aromatic radical, by reacting this amino group with carboxylic acid or sulfonic acid chlorides, with chlorocarbonic acid esters, isocyanates or mustard oils in a manner known per se.

The individual procedures for preparing the active ingredients according to the invention are illustrated below: If a compound of the formula II with R1n-ethyl is used as the starting material, the course of the reaction can be reproduced as follows: With l-deoxynojirimycin of the formula V and formaldehyde as starting materials, the following equation results: With benzaldehyde as the carbonyl component, the reductive alkylation is carried out as follows: Assuming acid amides of the formula VII, the reaction can be described as follows: Urethanes of the formula Vm- - optionally as derivatives provided with hydroxyl protective groups - can be reduced to N-tflethyl-l-deoxynojirimycin with LiAlH4: For the reaction of I-deoxynojirimycin with alkylating agents, the reaction with allyl bromide is given as an example: Some of the compounds of the formula II used as starting materials are known. This is the case when R3 = H, -CH2OH or -CH2NH2 and R1 = H. Other compounds of the formula II and IIa are new; however, they can be prepared from compounds known from the literature by processes known per se.

For example, from the compound of the formula X, which is known from the literature go out and react these with carbonyl compounds of the formula VI in the presence of a hydrogen donor reducing agent to give compounds of the formula II.

The compound X can also be used with reactive acid derivatives to acid amides or urethanes and uraset these with an amide reducing agent reduce to amines.

This is illustrated by an example: The compound of the formula X can also be reacted with reactive alkylating agents of the formula IX Z - Rt IX to give compounds of the formula II.

In addition, instead of the compound X, known partially protected derivatives of the formula XI can also be used in the abovementioned reactions.

and then the trityl and benzyl protective groups in a known way, for example with sodium in liquid; .oniak, remove. To prepare compounds of the formula II, the compound of the formula XII, which is likewise known from the literature, can also be used be reacted with amines of the formula XIII R1 - NH2 XIII in the presence of a hydrogen donor reducing agent, for example in the presence of NaSH3CN.

This reaction usually results in a mixture of diastereomers. The undesired diastereomer is optionally at this stage or on a later stage by the usual chromatographic methods or by fractional crystallization separated. Finally, the trityl and benzyl protecting groups split off in a known way, for example with sodium, in liquid ammonia.

Furthermore, new compounds of the formula II or

IIa also obtained by using the literature-known degradation products of D-glucose of the formulas XIV to XVI with reagents with a carbanine character such as, for example, alkyl-Li or Grignard compounds or the Li salt of 1,3-dithiane to react and the compounds of the formula XVII converts in a manner known per se CS.INOUYE et.al., Tetrahedron 23, 2125-2144J via the ketone and the oxime into the amine, a mixture of gluco and ido compounds usually being formed from which the desired gluco-Verbinaur.g XVIII can be isolated by the usual chromatographic methods.

The removal of the benzyl protecting group by catalytic hydrogenation or with Na in flassi.gen NH3 then gives the compounds of the formula II.

Compounds of the formula XIX are obtained if the aldehydes of the formulas XIV to XVI are reacted in a manner known per se with amines and hydrocyanic acid to give aminonitriles, for example XVI to give XIX Here too, as a rule, the desired gluco compound has to be separated from the ido compound by customary chromatographic methods. The further modification of the nitrile group by hydrogenation or hydrolysis before or after the removal of the benzyl protective group leads to further compounds of the formula II.

The reaction of XIV to XVI with CH-acidic compounds such as nitroalkanes, alkyl nitriles, CH-acidic esters or ketones can also lead to compounds of the formula II. This gives unsaturated compounds, for example of the formula XX, either directly or by dehydrating the aldol addition products, X = -NO2, -CN, -COOAlkyl Y = H, alkyl, aryl XX which by Michael addition of amines after chromatographic separation of gluco and ido isomers yield compounds of the formula IIa.

The splitting off of the isopropylidene protective group from the compounds of formula II takes place in a moderately strongly acidic to weakly acidic solution, preferably in a pE range between 1 and 4, in a hot solution or in a solution with water miscible, water-based organic solvents. As acids can be diluted Mineral acids such as sulfuric acid or organic acids such as acetic acid be used. The reaction is preferred at atmospheric pressure and temperature carried out between room temperature and the boiling point of the solvent.

To work up the reaction mixture, the acid is neutralized and separated off as a salt or with the aid of a basic ion exchanger. The isolation of the compounds of the formula I where R2 = OH is then carried out, if appropriate, by a gentle process Removal of the solvent, for example by lyophilization.

A preferred embodiment of the splitting off of the isopropylidene protective group from compounds of formula II consists in dz one the aqueous or water-containing alcoholic solution of the compounds of formula II with SO2 saturates and several days stored at temperatures between CO and d gCCC. The compounds of formula I Then fall as well crystallizing bisufite adducts (R2 = -SO3H), from which the compounds of formula I can be obtained with the aid of e.g.

-prigem Ba (OH) 2 can be released.

The reduction of compounds of the formula I with R2 = OH to give compounds of the formula I with R2 = H takes place through the use of alkali metal borohydrides, alkali metal cyanoborohydrides or also of dialkylaminoboranes. The use of sodium borohydride is preferred in aqueous solution or in a water-miscible organic water-containing solution Solvent, such as dioxane, at room temperature or where appropriate elevated temperature.

However, the reduction is very particularly preferably carried out catalytically with Pt or Pd as a catalyst or in the presence of Raney Ni. That's where you work preferably in aqueous solution at room temperature.

The starting product of the formula V with R3 = -CH2OH is known and will be either by catalytic hydrogenation from the nojirmycin obtainable by fermentation [s. S.INOUYE et.al., Tetrahedron 25, 2125-2144 (1968)] or by extraction from Mulberry bark (see DT-OS 2 656 602) or fully synthetic gexfonnen. After a new advantageous 1-Deoxynojirimycin can also be produced by using organisms of the family Bacillaceae in usual nutrient solutions at temperatures of about 15 to about 80 ° C. for about 1 to about 8 days with aeration in conventional fermentation vessels cultured, the cells spun off and the deoxy compound from the culture broth or the cell extracts isolated by conventional purification processes. German patent application P 26 58 563.7 - (Le A 17 587)].

The carbonyl compounds of Formula VI are either known or can be manufactured according to standard processes.

Typical examples that may be mentioned are: straight-chain or branched-chain Alkyl aldehydes such as formaldehyde, acetaldehyde, n-propanal, n-butaral, 2-methylpropanal, n-pentanal, 2-methylbutanal, 3-methylbutanal, 2,2-dimethylpropanal, n-hexana 1, 2-ethylbutanal, n-hptanal and n-octanal; Alkenyl aldehydes such as propanal, 2-methylpropanal, 2-butanal, 2-methyl-2-butenal, 2-ethyl-2-hexenal; Cyclic aldehydes such as cyclopropanecarbaldehyde, Cyclopentane carbaldehyde, cyclopentane acetaldehyde, cyclohexane carbaldehyde, benzaldehyde, o-, m- and p-toluene carbaldehydes and phenylacetaldehyde; substituted by hydroxy straight and branched chain alkyl aldehydes such as 5-hydroxypentanal, 2-hydroxy-3-methylbutanal, 2-hydroxy-2-methylpropanal, 4-hyaroxybutanal, 2-hydroxypropanal and 8-hydroxyoctanal; straight and branched chain alkyl aldehydes substituted by amino such as 5-aminopentanal, 2-aminopropanal, 3-aminopropanal, 4-aminobutanal, 2-amino-3-methylbutanal, 8-aminooctanal and mono-N-alkyl derivatives thereof; and straight disubstituted by amino and hydroxy and branched chain Alkyl aldehydes such as 2-hydroxy-5-aminopentanal, 3-hydroxy-3-methyl-4-aminobutanal, 2-hydroxy-4-aminobutanal, 2-hydroxy-3-aminopropanal, 2-hydroxy-2-methyl-3-aminopropanal, 2-amino-3-hydroxyoctanal and mono-N-alkyl derivatives of that.

Furthermore: methoxy-acetaldehyde, ethoxy-acetaldehyde, n-propoxy-acetaldehyde, 1-propoxy-acetaldehyde, n-butoxy-acetaldehyde, i-butoxy-acetaldehyde, tert-butoxy-acetaldehyde, Cyclopropylmethyloxy-acetaldehyde, cyclopropoxyacetaldehyde, 2-methoxy-ethoxy-acetaldehyde, 2-ethoxy-ethoxy-acetaldehyde, 2-methoxy (1-methoxy-ethoxy) -acetaldehyde, 2-ethoxy (1-methyl-ethoxy) -acetaldehyde, Phenyloxyacetaldehyde, 2-methoxy-2-methyl-acetaldehyde, 2-ethoxy-2-methylacetaldehyde, 2-n-propoxy-2-methyl-acetaldehyde, 2- (i-propoxy-) 2-methyl-acetaldehyde, 2- (n-butoxy) -2-methyl-acetaldehyde, 2- (i-butoxy) -2-methyl-acetaldehyde, 2- (tert-butoxy) -2-methylacetaldehyde, 2-cyclopropylmethyloxy-2-methyl-acetaldehyde, 2-Cyclopropyloxy-2-methyl-acetaldehyde, 2-methoxy-ethoxy-α-methyl-acetaldehyde, 2-ethoxy-ethoxy-α-methyl-acetaldehyde, 2-methoxy- (1-methyl-ethoxy) α-methyl-acetaldehyde, 2-methoxy-2,2-dimethyl-acetaldehyde, 2-ethoxy-2,2-dimethylacetaldehyde, 2-cyclopropylmethoxy-acetaldehyde, 2 - # - butoxy-2,2-dimethyl-acetaldehyde, methylthio-acetaldehyde, ethylthio-acetaldehyde, n-propylthioacetaldehyde, i-propylthio-acetaldehyde, cyclopropylmethylthio-acetaldehyde, 3-methoxy-propanal, 3-ethoxypropanal, 3-n- and 3-i-propoxy-propanal, 3-n-, 3-i- and 3-tert-butoxy-propanal, 3-cyclopropyloxy-propanal, 3-cyclopropylmethyloxy-propanal, 3-methoxy-3-methyl-propanal, 3-ethoxy-3-methyl-propanal, 3-n- and 3-i-propoxy-3-methylpropanal, 3-n-, 3-i- and 3-tert-butoxy-3-methyl-propanal, 2,3 and 4-methoxy-butanal, 2,3 and 4-ethoxy-butanal, 2-methylthio-propanal, 2-ethylthio-propanal, 3-methylthiopropanal, 3-ethylthio-propanal, 2-methylthio-butanal, 3-methylthio-butanal, 4-methylthio-butanal, Furfural, tetrahydrofurfural, thiophene, 5-bromothiophene, 5-methylfurfural, pyranocarbaldehyde.

Also mentioned as ketones are, for example: acetone, methyl ethyl ketone, Methyl-n-propyl ketone, diethyl ketone, methyl butyl ketone, cyclopentanone, di-n-propyl ketone, Cyclohexanone, 3-methylcyclohexanone, 4-methylcyclohexanone, acetophenone, propiophenone, Butyrophenone, phenylacetone, p-methoxyacetophenone, m-nitroacetophenone.

An example of a hydrogen-donor reducing agent is formic acid use (Leuckart-Wallach reaction).

The formic acid is used in large excess.

With formaldehyde as the carbonyl component, the reaction can be carried out in an aqueous Be carried out with ketones and less reactive aldehydes in solution anhydrous formic acid. The reaction temperatures are between 100 and 2000 ( if necessary, the reaction must be carried out in an autoclave.

The hydrogen donor reducing agent can also be catalytically excited Use hydrogen. The main catalyst used is Raney nickel however, noble metal catalysts can also be used. The response is in the generally at pressures between 80 and 150 atmospheres H2 pressure and temperatures carried out between 70 and 150 ° C. Protic, polar, Solvents 1, especially alcohols, are preferred.

Alkali metal cyanoborohydrides are also used as hydrogen donor reducing agents, Dialkylaminoboranes and alkali metal borohydrides are used. Particularly preferred in this process variant is the use of sodium cyanoborohydride.

The reaction is generally carried out at room temperature. However, it can also be advantageous to heat to the reflux temperature.

The process is usually carried out in an inert. Solvent carried out. Although anhydrous aprotic solvents can be used (e.g. tetrahydrofuran, if the reducing agent is morpholinoborane) it usually becomes protic after all Solvent used.

A lower alkanol is particularly suitable as such. But it can also water or an aqueous lower alkanol (e.g. aqueous methanol or ethanol) or other aqueous solvent systems such as aqueous dimethylformamide, aqueous Hexamethylphosphoric acid tetramide, aqueous tetrahydrofuran or aqueous ethylene glycol dimethyl ether be used.

The process is usually carried out in a pH range of 1 to 11, a pH range between 4 and 7 is preferred.

The acid amides of the formula VII and urethanes of the formula VIII are for Part known or can be prepared according to known methods from compound V and reactive Acid derivatives, which can also be formed in situ from the free acids, are obtained will.

The reaction can be carried out in such a way that only the amino group of the compound V reacts with the acid derivative, for example by using excess acid anhydride in an aqueous or alcoholic solution or in such a way that the peracylated compounds are initially formed, which then by reaction with alcoholic ammonia or can be converted into the N-acylated compounds by alkali metal alcoholate-catalyzed transesterification. The latter procedure is explained using an example: The acid amides of the formula II can be reduced to amines of the formula I (R = H) with complex metal hydrides or with hydrogen boride compounds. The use of NaBH4 in pyridine or also of sodium acyloxyborohydrides, especially that of sodium trifluoroacetoxyborohydride, is preferred. The reducing agents are usually used in excess. Sodium trifluoroacetoxyborohydride is generated in situ from sodium borohydride and trifluoroacetic acid. In addition to pyridine, possible solvents are polar aprotic solvents such as dioxane, tetrahydrofuran or diglyme. The reaction is preferably carried out at the boiling point of the solvent. If appropriate, LiAlH4 can also be used for the reduction, preferably when the hydroxyl groups are previously protected in the usual ways.

The reactive alkylating agents of the formula IX are known or can can be produced according to common methods. The implementation with the compound V takes place in iner + en organic solvents at room to boiling temperature with or without Addition of an acid-binding agent.

Individual compounds of the formula are listed as new active ingredients Compounds of the formula R1 Rx OH3 - H- OH2- H- CH3CH2CH2- H- CHtCH2) 6) 6-0H2- H- H, H3C-O-CH2- H'02 -0-OH2- H- H, H3C-COO-CH2- OOO-0H2 - H- H2I-CH2- CH3 c; -r, CO-NH-OH2 - V3-MEI-CH, - OH3 H- O OH3 NHOONH-0H2 - H- b NHCONH-CH2- OH3 -OH2 -NO-NH-0H2 - tI 5 H- H5 OCONH-0H2 - HC-CH2 -CH2 - - ps E.- ~ j H- COOK H- H3 C-502 -'T-CH2 - H H3 H3 CH C C-SOG -N-OH2 - H II-% ffiSO2 £ TOH2 - CE - C TJ ~ CLY, - C: i, CE; 2 ~ CH3 - OH OH2 OH2 - CH3 CL, (C ii,) (OH) 6OH2 OH3- H3 C - "- CH2 - CH3 X5 ~;) H5 2 -0-OH - OH3- TH3 -I, 0-000-OH2- OH3 - »'' OO-C4X2- CH3 - H2N-CH2- 0H3 - CH3 CO - NH-CH, - E. C-3 t ~ uC0-! CH2 CEIi Oj - CO-N-CH2- 0H3 - OH3NHOC? -C4- OF3 - 8 Iv ON nC - - R1 R3 SH, OH3 -OH2 -NC-NH-0H2 - F. Is C2 5 öOOH-CH2 - C, L, 3 - HOCH2 -Ch% - CE 'e CiI3- -OOi CH3 - -CONE2 OFr 3C - q0. - 0-SO -NC H H3 - F? I3 C O-H2 O-H2 0-SO2 -N-CH2 - H C.; 3- -N-0H2 - H Compounds of the formula The examples given below include, with regard to the configuration at the C-2 atom, α- and β-form R2 li- H N-CH - -T- CH, CC OO-Ntf-0H2 - H CM-CH2- - - - - / IvCO ~ N ~ wH2 - H- NHOONH-CH2 - »R ~ <N .'- CON-I'-CH2- H CH3-CH2-NC-NH-CH2- H ': .'- T- C2H5OCOIiH-C - r.- -CCOH C} 2 -5 - 2 , "T3C-SO2-N-CH2 H rI H3 C-H2 -h2 C-- C -H-CH2 2 - H h '- SO, -N-0H2 H fle-OH - R1 R2 H -f 2- & o0-cH2 ~ 02-000-OH2 - OH3- H2N-0H2- OH3 - C CO-NrrtOH - OH3 -) -CO-NH-CH2 - cH3 CH3 - CH, - czri, rJHCOT -; - CH - CH. - NHCONH-CH2 - cH3- CH3-CH2-N-CE - H 5 CH, - C2 H OCONH-CH2- -COOI-i Cr J ~ - - -COOC2 H5 C H3 -CONH2 CH3 - H3 C-So2 -N-CH2 - H OH - H3 (H3C-H20-H20-502-N-OH2- H OH3 - SQ -N-0H2 - H OH3 - HO-CH '- OH3-H5 C2 -COO-CH2 ~ CH3 - -OH 0H3 - SO3H C Hs ~ -CN R1 R2 CH3- -CCH3 CH3- -O-CH2-CH2-CH2-CH3-CH3- -SH CH3- -S-CH2-CH3 CH3- -NH2 CH3- -NH-CH3 Compounds of the formula The examples below with respect to the configuration at the C-2 atom, comprise both α- and ß-form R2 R2 -OH -O-CH2-CH2-CH2-CH3 -CH -SH -SO3H -S-CH2-CH3 -OCH3 -NH2 -NH-CH3 Compounds of the formula Compounds of the formula Compounds of the formula The earth-based inhibitors are suitable as therapeutics for the following indications: prediabetes, gastritis, constipation, caries, atheroskelerosis and especially obesity, diabetes and perlipoprotemia.

To broaden the spectrum of activity, it may be advisable to use inhibitors for glycoside hyirclases, which complement each other in their effect, to combine, be it that it is an encapsulation of the inhibitors according to the invention or combinations of the inhibitors according to the invention with already known ones. For example, it can be idle, saccharase inhibitors according to the invention to combine with already known amylase inhibitors.

In some cases, combinations of those according to the invention are also advantageous Inhibitors with known antidiabetics (ß-cytotropic sulfonylurea derivatives and / or blood sugar-active biguanide) scwie with blood lipid-lowering warkstoifan such as B. clofibrate, nicotinic acid, chelestyramine and others.

The compounds can be cloned without dilution, e.g. B. as powder or in a gelatin envelope or in combination with a carrier in a pharmaceutical Composition are applied.

Pharmaceutical grade preparations can be a larger or smaller amount the inhibitor onthaiten, e.g. B. 0.1% to 99.5%, in combination with a pharmaceutical compatible, non-toxic, inert carrier substance, the carrier substance being one or several solid, semi-solid or liquid dilution commat; middle, Fillers and / or non-toxic, inert and pharmaceutically acceptable formulation auxiliary may contain. Such pharmaceutical preparations are preferably in the form of dosage units of, d. H. physical-discrete, a certain amount of the inhibitor-containing units which are a percentage or a multiple correspond to the dose which is embidial to induce the desired inhibitory effect. The dosage units can be 1, 2, 3, 4 or more individual doses or 1.2, 1.3 or 1.4 of a Finzeldose included. A single dose preferably contains a sufficient amount Amount of active ingredient to be used in an application according to a predetermined dosage regimen to achieve the desired weighting of one or more desing units, being a whole, a half, or a third or a quarter of the T @ gosd @ sis usually is given to all main and additional meals during the day.

Other therapeutic agents can also be taken. Though the dosage and dosage regimen in each. Case should be weighed carefully, using thorough professional judgment and taking into account the age, the condition and condition of the patient, the type and severity of the disease, the dosage will usually be in a range between about 1 to about 1 × 10 4 YOU / kg of body weight per day. In some cases you become one sufficient therapeutic effect can be obtained with a lower dose while in other cases a larger dose will be required.

Oral application can be made using solid and liquid dosage units been carried out, such as B. powder, tablets, dragges, capsules, granules, Suspensions, solutions and the like.

Powder is made by crushing the substance into a suitable size and mixing with a likewise crushed pharmaceutical carrier. Although an edible carbohydrate such as B. starch, lactose, sucrose or glucose normally for this purpose use f inet and can also be used here, is it desirable to have a non-metabolizable carbon content such as B.

to use a cellulose derivative.

Suts, flavor additives, preservatives, disguising agents and coloring agents can also be included.

The capsules can be prepared by preparing the powder mixture described above and by filling already formed gelatine casings. The powder mix you can before the filling process with lubricants such. 3. silica gel, talc, magnesium stearate, Add calcium stearate or solid polyethylene glycol. The mixture can be wasted with a disintegrator or solubilizer, such as. B.

Agar agar, calcium carbonate or sodium carbonate add to the Taking the capsule will improve the accessibility of the inhibitor.

The tablets are made, for example, by manufacturing a powder mixture, coarse or fine-grained, and the addition of a lubricant and Disintegrators. This mixture is used to form tablets. Prepare a powder mix one before by mixing the substance, which has been comminuted in a suitable manner and supplements a diluent or other carrier as described above. If necessary, a binder is added: e.g. B. carboxymethyl cellulose, alginates, gelatin or pelyvinyplyrronlidone, a solution retarder such as e.g. B. paraffin, a resorption accelerator such as B. a quaternary salt and / or a Adsorptive agents, such as B. bentonite, kaolin or dicalcium phosphate. The powder mixture can be granulated weden together with a binding agent such. B. syrup, starch paste, acacia slime, or solutions made from cellulosic or polymeric materials. Then you p @@ eat the product through a coarse sieve. As an alternative to this, the powder mixture can be mixed with a Let the tablet machine run and the resulting unevenly shaped Chop pieces down to grain size. So that the resulting grains do not get into the tablet-forming nozzles stick, you can add a lubricant to them, such as B. stearic acid, stearate salt, talc or mineral oil. This made slippery The mixture is then compressed into tablet form. The materials can also be free-flowing inert carriers are combined and brought directly into tablet form omitting the granulate or crushing steps. You can get the product provided with a clear or opaque protective cover, e.g. B. a shellac coating, a coating of growth or polymer substances and a polished shell made of wax. Dyes can be added to these coatings, so between the different ones Dosage units can be differentiated.

The preparation forms to be administered orally, such as. B. Solutions, Syrup and Elixire can be prepared in dosage units, so that a certain Mange preparation contains a certain amount of active ingredient. Syrup can be made like this be that the active ingredient in an aqueous solution, which suitable flavorings contains, is dissolved; Elixirs are made using non-toxic, alcoholic Carriers received. Suspensions can be obtained by dispersing the compound in represent a non-toxic carrier. Solubilizers and emulsifiers, such as B. ethoxylated Isostearzlalkohole and Polyoxyäthylenschbitester, preservatives, Schmachsverbesserbde additions such. B. peppermint oil or saccharin and the like. can also be admitted.

Dosage instructions can be indicated on the capsule.

In addition, the dosage can be assured that the active ingredient is released with a delay, e.g. by keeping the active ingredient in polymer substances, Waxes or the like.

In addition to the pharmaceutical compositions mentioned above foods containing these active ingredients can also be produced: for example Zucher, bread, potato products, fruit juice, beer, chocolate and other Kenfekvartikel, and canned goods, such as B. jam, with these products being a therapeutic-gentle Amount of at least one of the invention. Inhibitors was given.

Those produced using the ingredients according to the invention Foods are also suitable for dieting in patients suffering from metabolic disorders suffer as well as for the nutrition of healthy people in terms of metabolic disorders preventive diet.

The inhibitors according to the invention also have the property on, in animals the ratio of the proportion of unwanted fat to the proportion of Desired low-fat meat (lean meat) in favor of lean meat to a great extent. This is of particular importance for the uproar and keeping of farm animals, e.g.

B. in pig fattening, but nuch ven of considerable importance for the Raising and keeping of other useful and ornamental animals. The utilization of the inhibitors can v @ iterhin lead to an appreciable rationalization of the feeding of the animals, in terms of both quantity and quality. As they have a gavisse 'delay The effect of digestion is the length of time that nutrients remain in the digestive tract lengthened, ad libitum feeding is possible will. Furthermore, the result is the use of the inhibitors according to the invention in many cases the need to spar in valuable protein feed.

The active ingredients can thus be used in practically all areas of animal nutrition as a means of reducing fat deposits as well as saving on feed protein be used.

The effectiveness of the active ingredients is largely independent of this the species and gender of the animals. The raw materials prove to be particularly valuable in animal species that lead to increased fat storage at all or in certain phases of life tend.

As animals in which the inhibitors are used to reduce fat deposits and / or can be used to save feed protein, for example the following livestock and ornamental animals are named: Warm-blooded animals such as cattle, pigs, horses, Sheep, goats, cats, dogs, rabbits, fur animals, e.g. B.

Mink, chinchilla, other ornamental animals, e.g. B. guinea pigs and hamsters, Laboratory and zoo animals, e.g. B. rats, mice, monkeys, etc. Gaflügel, z. B. Broilers, Hünmer, Geese, ducks, turkeys, pigeons, parrots and canaries and Celtic bloods, such as Fiche, e.g. 3. carp ur. Reptiles, e.g. B. Slim.

The amount of active ingredients. the animals to achieve the desired Effect is administered, can because of the favorable properties of the active ingredients be largely lost. It is preferably about 0.5 mg to 2.5 g, in particular 10 to 100 mg / kg feed per day. The duration of administration can range from a few hours or days up to several years. The right amount of active ingredient like that suitable duration of administration are closely related to the feeding goal. They depend in particular on the type, age, gender and state of health and the way the animals are kept and can easily be determined by any specialist.

The active compounds according to the invention are used in animals like the usual ones Wetnodes administered. The type of administration depends in particular on the type of the behavior and general condition of the animals. Administration once or several times a day, at regular or irregular intervals, orally. For reasons of expediency, the zeister. Cases of oral administration, inesendere in the rhythm of the food and / or drink intake of the animals, forgiven.

The active ingredients can be administered as pure substances or in formulated form The formulated form is used both as a pretix and as a mixture with non-toxic ones inert carriers of any kind, as well as part of a total ration in the form of a fine feed or as a constituent part of a single compound feed understand is. The application of suitable preparations is also included about the drinking water.

If appropriate, the active ingredients can also be used together in formulated form with other nutrients and active ingredients, e.g. B. mineral salts, trace elements, vitamins, Proteins, energy sources (e.g. starch, sugar, fats), colorants and / or Flavorings or other feed additives, such as. B.

Growth promoters, are administered in a suitable form. The active substances can be given to animals before, during or after feeding.

Oral administration together with the feed is recommended and / or drink water, weboi je nech Pedarf the active ingredient of the total amount or only Parts of the feed and / or drinking water are added.

The active ingredients can be mixed simply by customary methods as pure substances, preferably finely divided Form or in formulated form in a mixture with edible, toxic carrier substances, if necessary also in the form of a premix or a feed concentrate, the feed and / the dem Drinking water to be added.

The feed and / or drinking water can for example be according to the invention Active ingredients in a concentration of about 0.001 to 5.0%, in particular 0.02 to 2.0% (weight) included. The optimal level of concentration of the active ingredient in the Feed and / or drinking water is particularly dependent on the amount of feed - and / or drinking water intake of the animals and can easily be determined by any person skilled in the art will.

The type of feed and its composition is beer without Beleng. All common, customary or sperial feed compositions can be used are used that preferably include the usual, for a balanced diet, Necessary balance of energy and protein, including vitamins and mineral stiffeners. The feed can be composed, for example from vegetable substances, e.g. B. Oilcake meal, grain meal, grain by-products, but also from hay, fermented fodder, beets and other fodder plants, from animal substances, z. B. Meat and fish products, bone meal, fats, vitamins, e.g. B. A, D, E, K and B complex and special source of protein, e.g. B. yeasts and crooked amino acids and minerals and trace elements such as B. phosphorus and iron, zinc, manganese, Copper, cobalt, Jed use.

Promixes can preferably be about 0.1 to 55%, in particular 0.5 to 5.0% (weight) e.g. N-methyl-l-deoxynojirimacin meban be @@ ebiggen edible carriers and / or mineral salts, e.g. carbonate feed lime and are used according to the common mixing methods.

Compound feeds preferably contain 0.001 to 5.0%, in particular 0.02 up to 2.0% (weight), for example, of N-methyll-deoxynejirimycin in addition to the usual Raw material components of an egg feed, e.g. B. grain meal or by-products, Ölluchonschort, animal protein, minerals, trace elements and vitamins. she can be produced using the usual mixing methods.

The active ingredients can preferably be used in premixes and veal feedstuffs Gegebonenfels also beecheden suitable means due to their surface, e.g. B. with non-toxic waxes or gelatine protected from air, light and / or Pauchtingkeir will.

Babeispiel - for the composition of a ready-to-use compound feed for Poultry containing an active ingredient according to the invention: 200 g wheat, 340 g corn, 360.3 g soy meal, 60 g beef tallow, 15 g dicalcium sulfate, 10g calcium carbonate, 4 g jodfertes @@ be salt, 7.5 g vitamin-mineral mixture and 3.2 g active ingredient premix result in 1 kg of feed after careful mixing.

The vitamin-mineral mixture consists of: 6000 I.U. vitamin A, 1000 I.U. vitamin D3, 10 mg vitamin E, 1 mg vitamin K3, 3 mg riboflavin, 2 mg pyridoxine, 20 meg vitamin B12, 5 mg calcium pantothenate, 30 mg nicotinic acid, 200 mg chelin chloride, 200 mg Mn So4 x H2O, 140 mg Zn SO4 x 7H2O, 100 mg Fe SO4 x 7H2O and 20 mg Cu SO4 x 5H2O.

The active ingredient premix contains z. B. N-Nethzkl-1-deoxynejirizycin in the desired size, e.g. B. 1600 mg and an additional 1 g of DL-methionine and so much soybean meal that 3.2 g premix is produced.

Example of the composition of a mixed feed for pigs, the ainen Active ingredient of formula I contains: 630 g of meal meal (made up of 200 g corn, 150 g barley, 150 g oats and 130 g weirenschret), 80 g fish meal, 60 g soy meal, 58.8 g tapioca flour, 38 g brewer's yeast, 50 g vitamin-mineral mixture for pigs (composition, e.g. like bien chick feed), 30 g flax cake flour, 30 g corn killer feed, 10 g soybean oil, 10 g canned molasses and 2 g active ingredient premix (Composition e.g. for chick feed) result in 1 kg after careful mixing Lining.

The given feed mixtures are preferably for rearing and Masr of chicks or Pigs matched, but they can be similar or similar Together they can also be used for rearing and fattening other animals.

The inhibitors can be used individually or in any desired mixture can be used with each other.

Saccharase inhibition test in vitro The saccharase inhibition test in vitro enables the enzyme-binding activity of a substance to be determined by comparing the activity of the solubilized intestinal dis @ ocharidase complex in the presence or in the absence (so-called 100% value) of the inhibitor. Las substrate, which determines the specificity of the inhibition test included a practically glucose-free sucrose (glucose> 100 ppm), the enzyme activity determination is based on the spectrophotometric determination of released glucose by means of Glucose dehydrogenase and nicotinamide adenine dinucleotide as cofactors.

One sucrose inhibitor unit (SIE) is defined as those inhibitory activity, which in a defined test approach a predetermined saccharolytic activity reduced by one unit (sucrose unit = SE); the sucrose unit is defined as that enzyme activity which Under given conditions, one µmol saccharode per minute cleaves and thus for Release of one µmol each of glucose, which is determined in the test, and fructose, which is not recorded in the test leads.

The intestinal disaccharidase complex is derived from pig small intestine mucosa by tryptic digestion, precipitation from 66% ethanol at -20 ° C, taking up the Precipitate in 100 mM phosphate buffer, pH 7.0 and subsequent dialysis against the same buffer won.

10 µl of a sample solution which is prepared in such a way that the extraction of the test batch at least 10%, but not more than 25% below that of the 100% value are with 100 µl of a dilution of the intestinal disaccharidase complex in 0.1 M maleate buffer, pH 6.25, and preincubated for 10 min at 37 ° C. The dilution of the disaccharidase complex is to an activity of 0.1 SE / ml to adjust.

The saccharolytic reaction is then stopped by adding 100 µl of a 0.4 M solution of sucrose ("SERVA 35579") in 0.1 M maleate buffer, pH 6.25 started and after an incubation period of 20 min at 37 ° C by the addition of 1 ml of glucose dehydration reagent (1 vial of glucose dehydrogenase-muterotase mixture lyophilized ("XEROX 14053") and 331.7 mg ß-nicotinamide-adanine-dinucleotide (free Acid, "BOLMERINEER" purity grade I) dissolved in 250 ml 0.5X Tris buffer, pH 7.6) stopped. To detect the glucose, it is incubated for 50 min at 37 ° C. and finally photometry at 340 nm against a reagent blank (with enzyme, but without sucrose).

The calculation of the inhibitory activity of inhibitors is made more difficult because that even minor changes in the test system, for example a minor 100% value varying from determination to determination, from one that can no longer be neglected Influence on the tenders are. You get around these difficulties by working with runs a standard with each determination; a saccharase inhibitor is used as the standard of the formula C25H13O18N, which has a specific pinching activity of 77 700 SIE / g and when used amounts of 10 to 20 mg in the test to an inhibition specified above Order of magnitude leads. Knowing the difference in absorbance at 340 nm from The 100% value and the approach inhibited by the standard can be derived from the extinction difference of 100% value and the approach inhibited by the sample solution, taking into account the amount of inhibitor used in a known manner, its specific demmactivity calculated, expressed in sucrose inhibitor units per gram (SIE / g).

Specific saccharase-inhibiting activity in vitro 1-deoxynojirimycin 465,000 SIE / g N-methyl-1-deoxynojirimycin 2,330,000 SIE / g Preparation examples Example 1: N-methyl-1-deoxynojirimycin 3.2 g of 1-deoxynojirimycin and 2 ml of 30% aqueous formaldehyde are added to 4 ml of 98% formic acid while cooling with ice. The mixture is then refluxed for 8 hours. After the Ab.'ühlc-n, the reaction mixture is diluted with acetone. A resinous precipitate separates out. The acetone solution is decanted off and the L'arz is washed several times with acetone. The residue is then dissolved in distilled water and the solution is freed from formic acid by adding a basic ion exchanger in the (Amberlite JRA 410). The ion exchanger is filtered off and the aqueous solution is brought to dryness under reduced pressure. 3.0 g of resinous N-methyl-1-deoxynojirimycin remain. The compound can be further purified by chromatography on cellulose. Hydrous butanol is used as the flow agent.

Mass spectrum: The most important peak is found in the upper mass range at m / e = (M-CH2OH).

For further characterization, the compound is converted with acetic anhydride / pyridine 1: 1 at room temperature into the paracetylated compound, N-methyl-2,3,4-tetra-O-acetyl-1-deoxynojirimycin. A proton resonance spectrum of this derivative was measured in CDCl3 at 100 MHz: between # = 2.0 and 2.1 ppm there are 4 siglets for a total of 12 protons, which correspond to the methyl groups of the O-acetyl group The methyl group attached to N is found as a singlet at # = 2.45 ppm. Between # = 2.1 and 2.5 ppm, poorly resolved multiplets absorb two protons on a nitrogen-bonded carbon atom Another such proton appears as a doublet of a doublet (Ji = 11 Hz; J2 = 4 Hz) at # = 3.18 ppm.

At # = 4.16 and # = 4.22 ppm, a methylene group absorbs as an AB system. The remaining three protons by adding as a multiplet between # = 4.9 and 5.2 ppm.

Example 2: Nn-Butyl-1-deoxynojinimycin 12.5 ml of n-butyraldehyde, 0.01 mol of methanolic HCl and 1.5 g of NaCNBH3 are successively added to 3.2 g of 1-deoxynojirimycin (80.02 mol) in 40 ml of absolute methanol, while cooling with ice and stirring. The reaction mixture is stirred for 12 hours at room temperature. Then it is concentrated to dryness on a rotary evaporator.

The residue is dissolved in 50 ml of water and 3 times with 30 ml of CHCl3 each time extracted. The aqueous phase is brought to dryness again, the residue is taken up in 30 ml H2 O and applied to a 50 cm long and 2 cm wide column, those with a strong base ion exchanger in the OH # form (Amberlite RA 400 or Dowex 1 x 2) is filled.

It is eluted with water and the individual fractions are subjected to thin-layer chromatography examined. (Silica gel plates; mobile phase: ethyl acetate / methanol / water / 25% ammonia 100: 60: 40: 2; Spray reagent: KMnO2 solution. The fractions containing N-n-butyl-1-deoxynoj-rimycin contained are combined and the aqueous solution concentrated on a fraction evaporator.

Acetone is added to the residue, and crystallization occurs.

The crystals are sipped off, washed briefly with acetone and dried. There are 3 g of N-n-butyl-1-deoxynojirimycin with a melting point of 126-127 ° C obtain.

Mass spectrum: finds the most important peaks in the upper mass range one until m / e = 188 (M-CH2OH) and m / e = 176 (M-CH2-CH-CH3).

In the case of less reactive aldehydes, the reaction mixture was used Binding of the water of reaction Molecularsiweb 3 Å added.

The following were prepared analogously to this procedure: N-ethyl-1-deoxynojirimycin Measurement spectrum: Intense peak at m / e = 160 (M-CH2OH).

Nn Propyl-1-deoxyjirimycin Measurement spectrum: Intense peak at m / e = 174 (M-CH2OH).

Also peaks at m / e = 206 (M + H) and m / e = 204 (M-H).

N-iso-butyl-1-deoxynojirimycin Mass spectrum: The most important peaks in the upper mass range are wound at m / e = 188 (M-CH2OH), m / e = 176 m / e = 220 (M + H) and m / e = 218 (MH).

Nn-heptyl-1-deoxynojirimycin Measurement spectrum: The most important peak in the upper mass range is at m / e = 230 (M-CH2OH). There are also peaks at m / e = 262 (M + H) and 260 (mH).

N-Benzyl-1-deoxyjirimycin Mass spectrum: The most important peak in the upper mass range is found at m / e = 222 (M-CH2OH).

N- (2-pyridyl) methyl-1-deoxynojirimycin Mass spectrum: The most important peaks in the upper mass range are found at m / e = 255 (M + H), m / e = 236 (MHO) and m / e = 223 (m-CH2OH).

N-2-hydroxyethyl-1-deoxyjojirimycin Mass spectrum: The most important peak in the upper mass range is at m / e = 176 (M-CH2OH).

N-2,3-dihydroxy-n-propyl-1-deoxynojirimycin Mass spectrum: The most important peaks in the upper mass range are m / e = 206 (M-CH2OH) and m / e = 176. The substance is a mixture of two diastereomeric compounds. N- (S-ß-D-clucopyranosyl-2-mercaptoethyl) -1-deoxynojirimycin Mass spectrum: The mass spectrum was measured for the compound peracetylated in pyridine / ethiohydride.

The most important peaks in the upper kase area are found at m / e = 648 m / e = 568 and m / e = 344. The aldehyde required for the reaction was obtained from O-acetylated 1-thioglucose and chloroacetaldehyde. The acetyl groups were split off in the end product by transesterification with catalytic amounts of NaOCH3 in MeOH.

N-Oxiranyl-methyl-1-deoxynojirimycin Mass spectrum: The most important peaks in the upper mass range are found at m / e = 219 (M), m / e = 202, m / e = 188 (M-CH2OH) and r / e = 176 to the substance is a mixture of two diastereomeric compounds. N- (1-deoxynojirimycin-yl) acetic acid Mass spectrum: The most important peaks in the upper mass range are found at m / e = 203 (M-H2O), m / e = 159, m / e = 145 and m / e = 100.

The compound was not purified by chromatography via basic exchanger, but by recrystallization from methanol / water.

F.P. : 187-188 ° C.

No-nitrobenzyl-1-deoxynojirimycin Rf value: 0.85 (au; TLC prefabricated plates from Firserk Kieselgel 60; mobile phase: ethyl acetate / methanol / H2O / 25% ammonia 100: 60: 40: 2).

For comparison: Rf value of 1-deoxynojirimycin: 0.3.

N- (3-N-phthalimido-n-propyl) -1-deoxynojirimycin Mass spectrum: The most important peaks in the upper mass range were at m / e = 348, m / e = 319 (M-CH2OH), m / e = 301, m / e = 200, m / e = 188, m / e = 174 m / e 160 and m / e = 147 found. In this case, chromatography on basic ion exchangers was dispensed with and the compound was purified by boiling with acetone and recrystallization from ethanol.

FP: 208-210 ° C.

Mass spectrum: The most important peaks in the upper mass range are lower at m / e = 89 (M-CH2OH) and m / e = 146.

The compound was obtained from the above phthalimido compound by hydrazinolysis obtained in methanol.

No-carboxybenzyl-1-deoxynojirimycin Rf value: 0.7 (plates and superplasticizers as specified for the above connection).

For purification, the compound was as stated above via basic chromatographed, but eluting with 1% acetic acid at the end.

: -D-crboxybonzyl-1-desovnojirimycin Rf value: 0.7 (plates and flow agents as indicated above).

Here, too, the connection with 1% acetic acid became more basic Exchanger eluted.

Claims (22)

Claims 1) Compounds of the formula in which R1 represents H or an optionally substituted, straight-chain, branched or cyclic saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical and R2 represents -H, -OH, -OR ', -SH, SR', -NH2, - NHR ', NH2CH2-, NHR'-CH2-, NR'R "-CH2-, -COOH-, -COOR ', HO-CH2-, R" CO-NHCH2-, R'CO-NR "CH2-, R'SO2NHCH2- , R'SO2-NR "denotes CH2-, -SO3H-, -CN, -CONH2, -CONHR 'or -CONR'R" and R3 can assume the meaning given for Ri, preferably for -H, -CH3, -CH2OH , -CH2-NH2, NHR'-CH2-, NR'R "-CH2-, R'CONH-CH2-, R'CO-NR" CH2-, Hal-CH2-, R'O-CH2-, R ' COOCH2-, R'SO2O-CH2-, R'SO2NHCH2-, R'SO2-NR "CH2-, R'NH-CO-NH-CH2-, R'NHCS-NH-CH2-, R'O-CO- NH-CH2-, -CN, -COOH, -COOR ', -CONH2, -CONHR', -CONR'R ", where R ', R" can have the meanings given above for R1 and where for the case R3 = -CH2 and R2 = H or OH R1 is an optionally substituted, straight branched cyclic saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical, ie R1 is not H and in the case R3 = H and R2 = H, OH, SO3H, -CN and CH2-NH2 R1 is an optionally substituted, straight-chain branched or cyclis cher saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical, ie that R1 is not H and for the case R3 = -CH2-NH2 and R2 = OH R1 is an optionally substituted, straight-chain branched or cyclic saturated or unsaturated aliphatic hydrocarbon radical or an optionally substituted aromatic or heterocyclic radical, ie Rf is not H. 2. Compounds according to claim 1, in which R1, R 'and R "are an alkyl radical with 1 to 30, in particular 1 to 18, carbon atoms, an alkyl radical or an alkynyl radical 2 to 18, in particular 3 to 10 carbon atoms, a mono-bi- or tricyclic radical with 3 to 10 carbon atoms, which can be saturated, simply doubly unsaturated, one Aryl radical with 6 or 10 carbon atoms, a heterocyclic radical with 3 to 8, in particular 3 to 6 ring members containing 1, 2, 3 or 4 heteroatoms, in particular N, O, S can and to which a benzene ring or another heterocycle of the type mentioned may be condensed on, said radicals 1 to 5 in particular 1, 2 or 3 substituted can carry, 3. Compounds according to claim 1 and 2, in which R2 is -H, -OH, -SO3H, -CN, -CH2NH2, -CH2NH- [C1-C5-alkyl] or stands. 4. Compounds according to claim 3, in which R2 is -H, -SO3H or -CN stands. 5. Compounds according to claim 1 and 2 in which F; stands for -H. 6. Compounds according to claims 1 to 5, in which R3 is -H, -CH2OH, -CH5, -CH2NH2, -CH2-NH- [C1-C6-alkyl] or -CH2NH-CO- [C1-C6-alkyl]. 7. Compounds according to claim 1, in which R5 is -CH2OH. 8. Compounds according to claim 1, in which R2 is hydrogen and R3 stands for -CH2OH. 9. N- (n-heptyl) -1-deoxynojirimycin. 10. N-methyl-1-deoxynojirimycin. 11. N-ethyl-1-deoxynojirimycin. 12. N-Benzyl-1-dexoxynojirimycin. 13. N- (n-Butyl) -l-deoxynojirimycin. 14. N- (β-hydroxyethyl) -1-deoxynojirimycin. 15. Process for the preparation of compounds of the formula I. in which R1, R2 and R3 have the meaning given above, characterized in that nn compounds of the formula II or IIa in da: R1 and P have the meaning given above have, subjected to acid hydrolysis to remove the protective groups and the compounds of the formula I with R1 = -OH molated as such or, if appropriate, converted to further compounds of the formula I. 16. A process for the preparation of compounds of the formula I in which R1 and R3 have the meanings given above and R2 represents hydrogen, characterized in that compounds of the formula V are used a) with carbonyl compounds of the formula VI n which R1 is either H or has the meaning given above for R1 or are members of an alicyclic or heterocyclic ring, reacts in the presence of a hydrogen donor reducing agent or b) .it reactive alkylating agents of the formula IX IX in which R1 is the above for alkyl has the meaning given and Z represents a readily leaving group customary in alkylating agents, converts it and works up the batches in the customary manner. 17. Medicinal product, characterized by a content of a compound according to claims 1 to 14 and optionally pharmaceutically suitable additives. 18. A method for the production of a medicament, characterized in that that a compound according to claim 1, optionally using pharmaceutically formulated suitable additives. 19. Process for influencing the carbohydrate and / or lipid metabolism, characterized in that a compound according to claims 1 to 14 people or applied to animals. 20. Use of a compound according to claims 1 to 14 in the Treatment of obesity, diabetes and / or hyperlipemia. 21. Animal feed, characterized by a content of a compound according to claims 1 to 14 22. Use of a compound according to claims 1 up to 14 in animal nutrition.