CH636887A5 - Process for the preparation of novel immunological adjuvant compounds - Google Patents

Description

The present invention relates to a process for the preparation of new immunological adjuvant compounds of the formula:

CH2OR

NHCOR

t v

(I)

in which R, R1, R2, R6, X and Y have the meanings given in claim 1 and the wavy line means the a or β configuration or a mixture thereof,

if a wavy line means a, the other means ß.

The exclusion conditions specified in claim 1 are intended to preclude any overlap with Swiss Patent No. 613 709.

In the following formulas, the part that is represented by formula I in formula I:

(a)

is shown, for brevity and simplicity, as a grouping of the formula:

(b)

reproduced, wherein the compounds containing sub-formula b actually have the configuration of sub-formula a.

Those compounds of formula I in which X is L-alanyl, L-a-aminobutyryl, L-valyl, L-seryl, L-threonyl or L-prolyl and Y is D-isoglutamine are particularly preferred.

Those compounds of the formula I in which X is L-a-aminobutyryl, L-valyl, L-threo-ionyl or L-prolyl and Y is D-isoglutamine are very particularly preferred.

Those compounds of the formula I in which X denotes L-valyl or L-prolyl and Y denotes D-isoglutamine are even more preferred.

In the field of immunology, an injection of a vaccine or bacterial vaccine is usually required to achieve an immunological response in a patient that is sufficient to ward off a virus or bacterial infection. This is because the virus or bacterial antigen contained in the vaccine or bacterial vaccine is too quickly removed from the injection site by the animal or human patient and the patient does not have enough time to build up his immune response.

To delay the release of the virus or bacterial antigen and generally stimulate the patient's immunological systems, vaccines or bacterial vaccines were added to immunological adjuvants to avoid the need for multiple injections. However, many of these known immunological adjuvants, e.g. Kaolin, tragacanth, bentonite, carbopole, calciumphos-30 phatgele, tapioca, alum, aluminum hydroxide, calcium chloride, sodium alginate and the like, the disadvantage that they are not subject to metabolism after injection and thus themselves became a source of irritation.

It has long been sought for an immunological adjuvant 35 that is readily degraded by the patient's metabolism and at the same time delays the release of the antigen and generally stimulates the patient's immune response.

Immunological adjuvants commonly used in the laboratory are a) Freund's complete adjuvant (FCA), which is a suspension of killed whole Mycobacterium tuberculosis in mineral oil plus emulsifier, and b) Freund's incomplete adjuvant (FIA), which consists only of mineral oil plus emulsifier. In spite of the fact that Freund's complete adjuvant and Freund's incomplete adjuvant are used as standard laboratory samples, they are not used in practice because Freund's complete adjuvant is derived from the virulent microorganism Mycobacterium tuberculosis and Freund's incomplete adjuvant which does not contain any killed Mycobacterium tuberculosis high immunological response generated.

Ellouz et al., Biochemical and Biophysical Research Communications, Vol. 59, No. 4, pages 1317-1325 (1974) (see also BE-PS 821 385) disclose that certain peptidoglycans obtained from microorganisms have an immunological adjuvant activity and can be used in complete Freund's adjuvant instead of all of the killed Mycobate-rium tuberculosis.

The new peptidoglycans of formula I have significant immunological adjuvant activity, e.g. by antibody-6o pertiter to either bovine serum albumin (BSA) or ovalbumin [see WJ. Herbert, Chapter 20, Volume 1, Handbook of Experimental Immunology, Editor D.M. Weir, Blackwell Scientific Publications, Oxford (1973)] and delayed hypersensitivity to either bovine serum 65 albumin or ovalbumin [see J.H. Humphrey and R.G. White, Immunology for Students of Medicine, pages 493-545; F.A. Davis Co., Philadelphia, 3rd edition (1970)] or by delayed hypersensitivity to Arsanil-

636 887

acid / tyrosine [see S. Laskowitz, J. Exp. Med. 119, 291 (1963) and S. Laskowitz, Science 155, 350 (1975)], as described in more detail in Example 16. In addition, it has also surprisingly been found that the compounds of the formula I, when incorporated into a vaccine or bacterial vaccine which also contains a mineral oil or a vegetable oil, do not show the disadvantageous side effects which are usually observed when mineral and vegetable oils can be used in vaccines or bacterial vaccines that contain Freund's complete adjuvant.

Furthermore, the compounds of formula I per se have activity against infectious organisms, e.g. Klebsiella pneumoniae, Escherichia coli, Candida albicans or Staphylococ-cus aureus.

The new compounds of formula I are prepared according to the invention by the process defined in claim 1.

In the following reaction scheme, the

moderate processes and a preferred way to synthesize the starting materials illustrated. In the formulas, R3 is an acyl radical with 1 to 22 carbon atoms, R4 and R5 are identical or different acyl radicals with 1 to 22 carbon atoms, R6 is hydrogen or an alkyl radical with 1 to 16 carbon atoms, R7 is hydrogen or methyl, n is 1 or 2, Ph phenyl and X1 glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl, O-benzyl-L-seryl, O-benzyl-L-threonyl, L-methionyl, S-benzyl-L-cysteinyl, L-phenylalanyl, O-ben-lo zyl-L-tyrosyl, L-tryptophanyl, e-carbobenzyloxy-L-lysyl, 8-car-bobenzyloxy-L-ornithyl, the y-benzyl ester of L-glutamyl, L-glutaminyl, the β-benzyl ester of L-asparagyl, L-asparaginyl, L-prolyl or O-benzyl-L-hydroxyprolyl.

It can be seen that if in the compound of the formula 15 13 n = 1 or 2, the compounds thus obtained are those compounds of the formula I in which Y is D-isoasparagine or D-isoglutamine.

h2nçhcooh

ooh

(1)

h-nchcooh cooch2ph

(2)

(ch3) 3cochnchconh2

'fVn

COOCH, Ph

i

#

I.

(4)

(ch3) 3cochnchcooh

Wn

: oocH2Ph

(3)

hjnchconh, -

<k'n cooch2ph

HCl

(ch3j 3coc-x1-oh

(5)

(6)

(ch3) 3coc-x -nhchconh2

«RH2> n cooch2ph

h-x -nhchconh-

, I ^

(CHp) _ I d n cooch2ph hcl

(7)

(10)

5

636 887

Ph

H

, OCH.

och2ph niicoch.

(8th)

(8a)

och2ph

.och

6/7

rchcqor

CH2Ph nhcor

(9)

(8b)

CH2Ph nhcor h-x -nhchconh2

«RH2> n -HC1

cooch2ph

(10)

och

ÌCH2Ph nhcor r6ôîc-x1-nhchconh,

II I 0 <f2'n coocii2ph

(il)

636 887 6

7

636 887

An advantageous embodiment of the synthesis of the starting products and the process according to the invention is described in detail below.

First, a D-amino acid of Formula 1 with an aralkyl alcohol such as benzyl alcohol, p-methoxybenzyl alcohol, p-nitrobenzyl alcohol and the like, preferably with benzyl alcohol, in the presence of a strong acid such as hydrogen chloride, p-toluenesulfonic acid and the like, preferably sulfuric acid, at one temperature from about 0 to about 40 ° C, preferably from 20 to 25 ° C, for about 8 to about 40 hours, preferably for 14 to 18 hours, to obtain a compound of formula 2.

The amino group of the amino ester of formula 2 thus obtained is protected by blocking with a selectively removable group, such as the protecting groups well known in the field of polypeptide synthesis, commonly known as acyl, e.g. Formyl, trifluoroacetyl, phthaloyl and the like, urethane e.g. tert-butyloxycarbonyl, p-methoxybenzyloxycarbonyl, 2- (p-biphenyl) isopropyloxycarbonyl, isonicotinyloxycarbonyl and the like, sulfenyl, e.g. o-nitrophenyl-sulfenyl, tritylsulfenyl and the like, or alkyl, e.g. Tri-phenylmethyl, benzhydryl and the like. In particular, the protected amino ester of formula 3, namely the Na-tert-butyloxycarbonyl derivative, is prepared by reacting the amino ester of formula 2 with a suitable reagent, e.g. tert-butyl fluoroformate, tert-butyl azidoformate, tert-butyl phenyl carbonate or the like, preferably tert-butyl azidoformate, in an aqueous-organic mixture or in an anhydrous organic solvent, e.g. Dioxane, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide and the like, preferably anhydrous dimethyl sulfoxide, in the presence of a base, e.g. Sodium hydroxide, magnesium oxide, tetramethylguanidine, triethylamine and the like, preferably triethylamine, for about 12 to about 48 hours, preferably for 20 to 24 hours, at about 0 to about 40 ° C., preferably at 20 to 25 ° C. .

The carboxyl group of a protected amino ester of Formula 3 is activated by one of the reagents commonly used to form amide bonds, e.g. Dicyclohexylcarbodiimide, diisopropylcarbodiimide or another carbodiimide either with or without an additive, such as N-hydroysuccinimide or 1-hydroxybenzotriazole, isobutyl chloroformate or another chloroformate, 2-ethyl-5- (3-sulfophenyl or oxazol), 2 another 1,2-oxazolium salt, thionyl chloride or phosphorus pentachloride, 2,2'-dipyridyl disulfide / triphenylphosphine and the like, preferably isobutyl chloroformate, and with anhydrous ammonia in an anhydrous organic solvent, e.g. Dioxane, tetrahydrofuran and the like, preferably tetrahydrofuran, are treated for about 30 minutes to about 12 hours at about −20 to about +40 ° C., preferably over a period of one hour to about - 15 to about + 25 ° C warmed to give the compounds of formula 4, namely ß-benzyl-tert-butyloxy-carbonyl-D-isoaspartate (n = 1) or y-benzyl-tert-butyloxy-carbonyl-D-isoglutaminate (n = 2) .

The Na protecting group, as described above tert-butyloxy-carbonyl, is removed from the blocked isoaspartine-β-benzyl ester or isoglutamin-y-benzyl ester of the formula 4 by methods which are used for this class of protecting groups and are well known to the person skilled in the art are, e.g. by treatment with p-toluenesulfonic acid, methanesulfonic acid, hydrogen chloride, trifluoroacetic acid, formic acid, boron trifluoride or other moderately strong proton donors or electron acceptors in an inert organic solvent, preferably a saturated solution of hydrogen chloride in ethyl acetate, by treatment for about 1 to about 60 Minutes at about -15 to about +40 ° C, preferably for about

15 to about 30 minutes at about 15 to about 25 ° C, followed by a solvent with a low dielectric constant, e.g. Hexane, ether, benzene and the like, preferably ether, diluted, the compounds of the formula 5, näm-5 lent β-benzyl-isoasparaginate hydrochloride (n = 1) or y-benzyl-isoglutaminate hydrochloride (n = 2) be preserved.

The tert-butyloxycarbonyl compounds of the formula 6 are then reacted with the compounds of the formula 5 to give the compounds of the formula 7. This reaction is carried out in an io polar solvent, e.g. Ethyl acetate, acetonitrile, tetrahydrofuran, dimethylformamide and the like, preferably dimethylformamide, in the presence of a base, e.g. Triethylamine, diisopropylethylamine, N-methylmorpholine and the like, preferably diisopropylethylamine, is carried out and is obtained by adding suitable additives, e.g. the reagents described above for the preparation of the compounds of formula 4, preferably diisopropylcarbodiimide / l-hydroxy-benzotriazole, for a period of about 30 minutes to about 40 hours at about -10 to about +80 ° C, preferably about 30 to 20 minutes to about 1 hour at about 10 to about 25 ° C., whereby the Na-protected dipeptide of the formula 7 is obtained, in which n = 1 or 2 and X1 has the meaning given above. Other Na protecting groups can also be used in place of the tert-butyloxycarbonyl group shown in Formula 6, 25 e.g. the protecting groups described above for the preparation of compounds of formula 3.

The N-acetylglycopeptides of Formula 13, wherein R = R1 = hydrogen and R2 = methyl, n = 1 or 2 and X and R6 have the above meanings, are obtained as illustrated by the sequence of reactions from Formula 8 to Formula 13 runs.

The starting material for this reaction sequence is benzyl-2-acetamido-4,6-benzylidene-2-deoxy-a-D-glucopyranoside of formula 8, the production of which by P.H. Gross and R.W. Jeanloz 35 inj. Org. Chem. 32, 2762 (1967). In addition, all subsequent stages can be carried out equally well with the β-benzylglycoside of formula 8, the synthesis of which is also described in J. Org. Chem. 32, 2762 (1967). These steps are all carried out under conditions that are generally comparable to those described when starting from the a-benzylglycoside of Formula 8.

The alkylation of the free hydroxyl group of the compound of formula 8 can easily be achieved by first using a suitable base, such as sodium hydride, potassium hydride 45 and the like, in an inert organic solvent, such as dimethylformamide, tetrahydrofuran, dioxane and the like, at about 0 to about 50 ° C in the course of about 30 minutes to about 3 hours, preferably in dimethylformamide at about 10 to about 30 ° C in the course of about 15 to about 60 minutes, the corresponding anion forms. This anion is then, preferably in the same solvent, with a salt, e.g. the sodium salt, potassium salt and the like, an unbranched a-halocarboxylic acid having 2 to 18 carbon atoms; representative examples of such a-halocarboxylic acids 55 are chloroacetic acid, a-chloropropionic acid, a-bromopropionic acid, a-chlorobutyric acid, a-bromobutyric acid, a-bromovaleric acid, a-bromocaproic acid, a-bromocapric acid, a-bromomyristic acid and a- Bromostearic acid. This stage is advantageously carried out in dimethylformamide at about 20 to about 100 ° C. for about 15 60 minutes to about 5 hours, preferably at about 50 to about 80 ° C. for about 0.5 to about 2 hours , or at approx. 20 to approx. 30 ° C for approx. 10 to approx. 48 hours.

The resulting compounds of formula 9, wherein R2 = methyl, R7 = hydrogen and R6 has the meaning given above, are then isolated by conventional work-up methods and purified by crystallization or other methods known to the person skilled in the art.

The compounds of formula 9, wherein R2 = methyl, R7 =

636 887

8th

Hydrogen and R6 has the above meanings, but can also preferably be converted by conventional methods into the corresponding methyl esters of formula 9, in which R2 = R7 = methyl, which can then be converted by conventional methods, e.g. fractional crystallization or chromatography on silica. Processes for the preparation of the methyl esters are the reaction of the acids of the formula 9, in which R2 = methyl and R7 = hydrogen, with diazomethane in methanol, tetrahydrofuran, dioxane and the like, preferably in tetrahydrofuran at a temperature of about 5 to about 40 ° C. , preferably at about 20 to about 25 ° C, for about 5 minutes to about 2 hours, preferably about 15 to about 30 minutes, or with methyl iodide or dimethyl sulfate in the presence of a suitable base, for example Potassium carbonate, sodium hydroxide, triethylamine and the like, in a solvent such as tetrahydrofuran, dioxane, dimethylformamide and the like, at about 5 to about 50 ° C for about 30 minutes to about 16 hours. The esterification is preferably carried out in situ in the alkylation medium by adding water and dimethyl sulfate in succession and then reacting at about 20 to about 25 ° C. for about 14 hours to about 18 hours.

According to a further embodiment of this process, the alkylation of the free hydroxyl group of the compound of formula 8 takes place by reacting the anion thereof, which was prepared as above, with an ester, e.g. the methyl ester, ethyl ester, n-propyl ester and the like, an unbranched a-halocarboxylic acid having 2 to 18 carbon atoms; Examples of such a-halocarboxylic acid esters are methyl chloroacetate, methyl 2-bromopropionate, methyl 2-bromobutyrate, methyl 2-bromo caproate, methyl 2-bromo caprate, methyl 2-bromomyristate and methyl 2-bromostearate. This process is particularly useful for the preparation of compounds of formula 9, wherein R6 represents an unbranched alkyl group with 5 to 16 carbon atoms, and has the advantage that it proceeds directly to the methyl esters of formula 9, where R2 = R7 = methyl, which are purified by crystallization, chromatography on silica or other processes known to the person skilled in the art. This reaction is carried out in an inert organic solvent such as dimethylformamide, tetrahydrofuran, dioxane and the like at about 0 to 100 ° C. for about 15 minutes to about 24 hours, preferably in dimethylformamide at about 10 to about 30 ° C. for about 30 minutes to 2 hours. In some cases, higher yields of the compounds of the formula 9 are obtained if a solution of the anion of the compound of the formula 8 in dimethylformamide is added dropwise with stirring to a solution of the corresponding ester of the unbranched a-halocarboxylic acid.

The compounds of formula 9, wherein R2 = R7 = methyl, are then converted into the corresponding carboxylic acids of the formula

9, wherein R2 = methyl and R7 = hydrogen, by hydrolysis with a suitable base such as sodium hydroxide, potassium hydroxide, barium hydroxide and the like, preferably sodium hydroxide, in a mixture of water and a suitable organic solvent such as methanol, ethanol, Dioxane, tetrahydrofuran and the like, preferably methanol, at a temperature from about 20 ° C to the reflux temperature of the solvent mixture, preferably at about 60 to 90 ° C, for about 10 minutes to about 4 hours, preferably for about 15 Minutes to an hour.

The condensation of the compound of formula 9, wherein R2 = methyl and R7 hydrogen, with the various, suitably protected benzyl-a-aminoacyl-D-isoglutaminate and benzyl-a-aminoacyl-D-isoasparaginate derivatives of the formula

10, wherein X1 is glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, L-a-aminobutyryl, O-benzyl-L-seryl, O-benzyl-L-threonyl,

L-methionyl, S-benzyl-L-cysteinyl, L-phenylalanyl, O-benzyl-L-tyrosyl, L-tryptophanyl, e-carbobenzyloxy-L-lysyl, 8-carbo-benzylkoxy-L-ornithyl, the y-benzyl ester of L-glutamyl, L-glutaminyl, the β-benzyl ester of L-asparagyl, L-asparaginyl, L-prolyl or O-benzyl-L-hydroxypropyl and n = 1 or 2 is carried out according to various methods, which are known to the person skilled in the art of peptide synthesis. For example, the dipeptide hydrochlorides of the formula 10 are converted into the free base by adding a suitable, strongly basic tertiary amine, such as diisopropylethylamine. The resulting free amino compound corresponding to a compound of formula 10 is then linked to the carbonyl group of a compound of formula 9, e.g. R2 = methyl, R7 = hydrogen and R6 has the above meanings, condensed, e.g. a carbodiimide such as dicyclohexylcarbodiimide or diisopropylcarbodiimide in an inert organic solvent such as dimethylformamide, dichloromethane, ethyl acetate, dioxane, acetonitrile and the like. Optionally and preferably, the reaction is carried out in the presence of well known suitable additives such as 1-hydroxybenzotriazole, N-hydroxysuccinimide, p-nitrophenol, pentachlorophenol and the like. It has been found that condensation using diisopropylcarboddimide and 1-hydroxybenzotriazole in dimethylformamide at about 0 to about 50 ° C for about 2 to about 60 hours, preferably at about 10 to about 30 ° C for about 10 to approx. 40 hours, deliver excellent results. The resulting products of formula 11, wherein R6, X1 and n are as defined above, are isolated and purified by conventional methods, including crystallization and chromatography on silica. The free bases of the formulas 10 and 9, in which R7 = hydrogen, can also be condensed by other methods known to those skilled in the peptide art. For example, the use of mixed anhydrides of compounds of formula 9 in the presence of chloroformic acid esters, e.g. Isobutyl chloroformate, or l-ethoxycarbonyl-2-ethoxy-l, 2-dihydroquinoline effective. Other types of carbonyl activation, e.g. by using oxazolium salts or triphenylphosphine in the presence of dipyridyl disulfide or tetrahalocarbons are useful. A general summary of such condensation methods can be found in LS review articles. Klausner and M. Bodansky, Synthesis 453 (1972) and J.H. Jones, Chemistry and Industry, 723 (1974).

The sequence of reactions leading from the compound of formula 8 to a compound of formula 9, wherein R7 = hydrogen ,. leads can also be changed in such a way that the nature of the N-acyl function of the formula R2CO- can be varied. Thus, the N-acetyl function in the compound of formula 8 can be hydrolyzed with strong base, as described in J. Org.

Chem. 32,2762 (1967), whereby benzyl-2-amino-4,6-benzylidene-2-deoxy-a-D-glucopyranoside of the formula 8A is obtained. This reaction can also be applied to the β-anomer of Formula 8, as also described in J. Org. Chem. 32, 2762 (1967), and the resulting benzyl-2-amino-4,6-benzylidene-2-deoxy -ß-D-glucopyranoside can be used in subsequent reactions under essentially the same conditions as described starting from the compound of formula 8A. The selective N-acylation of the compounds of the formula 8A takes place by reaction with carboxylic acid anhydrides in a lower alcohol, preferably methanol. The anhydrides include those of unbranched and branched aliphatic carboxylic acids of the formula R2COOH, in which R21 contains from 21 to 21 carbon atoms and are optionally substituted by compatible substituents, such as methoxy, benzyloxy, halogen, e.g. Fluorine, or aryl groups with up to 10 carbon atoms, optionally by lower alkyl, lower alkoxy or halogen

5

to

15

20th

25th

30th

35

40

45

50

55

60

65

9 636 887

are substituted. Thus, the acyl group of the formula comprises acyl radicals and X, R2, R6 and n have the above meanings — R2CO — groups such as formyl (R2 = hydrogen).

provided using formic acid-acetic acid-The preferred acyl radicals contain unbranched or branched

drid), acetyl, trifluoroacetyl, methoxyacetyl, butyryl, isobutyl branched alkyl, aralkyl, alkylaryl or aryl radicals with 1 to 21 ryl, valeryl, octanoyl, lauroyl, myristoyl, palmitoyl, behenoyl, 5 carbon atoms, e.g. Acetyl, butyryl, isovaleryl, hexanoyl, phenylacetyl, benzoyl, p-fluorobenzoyl, p-methoxybenzoyl, octanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, behenoyl, naphthoyl, 7-methoxynaphthoyl and the like. The exact benzoyl, p-toluoyl, phenylacetyl, naphthoyl and the like. Conditions for selective N-acylation also depend on the selective synthesis of 4-0 and

Reactivity of the acid anhydride used. Developed in all-6-O-acyl derivatives of the formula 13, in which one of the common the reaction proceeds satisfactorily in methanol with io symbols R and R1 an acyl radical of the type defined above about 20 to about 65 ° C for periods of about 15 Minutes to means while the other (R1 or R) represents hydrogen about 6 hours, and most of the reactions can also and X, R2, R6 and n have the above meanings.

Unreflux is carried out for about 30 to about 60 minutes. When synthesizing all three types of compounds we will be the first. In the case of certain, highly reactive stage, the selective acid hydrolysis of the 4,6-O-benzylidene radio

Anhydrides, such as trifluoroacetic anhydride, use the reaction from the protected glycopeptide of formula 11, wherein X1, ion preferably using a slight excess R2, R6 and n have the above meanings. This shot of the anhydride in an inert solvent, such as hydrolysis, is carried out using a wide variety of acidic tetrahydrofuran. Treatments in the field of carbohydrate chemistry

The compounds of formula 8B are known from the above reaction. These include treatment with 50 to 90 ° C using sodium hydride and 20% acetic acid, formic acid or propionic acid at about 50 a sodium a-halogen carboxylate or an a-halogen car- to about 100 ° C or the short treatment with strong acids, bonic acid methyl ester in dimethylformamide as described above, such as approx. 90% trifluoroacetic acid, at room temperature. Alkylated above, with the various benzyl-2-acylamido-4,6- partially the reaction taking place using about 0-benzylidene-3-0- (l-carboxylakyl) -aD-glucopyranoside of 60% to about 80 % acetic acid at about 100 ° C during about 5 formula 9, wherein R7 = hydrogen and R2CO- and R6 the above- 25 to about 8 minutes. After a conventional workup gene meanings are obtained. The coupling of these is the completely protected 4,6-diol of the formula derivatives with the free base, which was isolated from the compound of formula 12A and was obtained by crystallization or chromatography with 10, according to the above for the manufacturer a suitable adsorbent, such as silica, cleaned, the compounds of formula 9, wherein R2 = methyl, the acylation of the two free hydroxyl groups of the methods described Ver and gives the blocked glycopeptide bond of formula 12A is carried out by treatment with 2 or tide of Formula 11, wherein the acyl group of Fomel R2CO-, the more molar equivalents of a conventionally aminoacyl group X1, n and R6 have the above meanings. activated acylating agent, such as an acyl anhydride,

The protective groups are removed from the blocked acyl chlorides, acyl cyanides or acylimidazolides in a glycopeptides of the formula 11 by catalytic hydro-suitable inert organic solvents in the presence of genolysis, preferably using a palladium 35 a tertiary base. Suitable solvents are pyridine, talysators. This reaction is normally carried out in an acidic methylene chloride, acetonitrile, dimethylformamide, tetrahydro medium under a hydrogen pressure of 1 to 2 atmospheres, dioxane and the like, while pyridine, triethyls at a temperature close to room temperature with amine, N- Methylmorpholine, diisopropylethylamine and the like-use of 5 to 10% palladium on carbon, palladium are suitable bases. The use of 2 to 10 moles of barium sulfate, palladium black or related catalyst equivalents of either the acyl chloride or the acyl analyzer was carried out. Preferably, a palladium on carbohydride in pyridine at room temperature while about 10 to about 10% catalyst in about 60 to about 90% aqueous acetic acid is generally advantageous for 24 hours, and the resultant is used. Under these conditions, the removal of all the 4,6-di-O-acyl derivatives of the formula 12E, in which R4 and R5 protective groups terminate within approximately 24 to approximately 72 hours and mean the same acyl radicals, which can in the same way as R and R1 if desired defined by thin layer chromatography 45, will be monitored by crystallization or chromatogra, using the glycodipeptide products, e.g. Phie isolated over an adsorbent, such as silica, and cleaned-2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-nigt. The removal of the protective groups from the compounds D-isoglutamine, the formula 13, in which R = R1 = hydrogen and the formula 12E is carried out by catalytic hydrogenolysis under R6 and R2CO- which have the above meanings, can be obtained using a catalyst derived from palladium, the , with the exception that if R2 in formula 11 means benzyloxy-50 as it stands above for the transfer of the compounds of methyl, the benzyl ether is split simultaneously, formula 11 into the compounds of formula 13, wherein R and R1 being compounds of the formula 13 can be obtained, in which R2 is hydrogen. The resulting hydroxymethyl means and X has the meaning given above. These products are compounds of the formula 13, in which R and R1 compounds are denoted by conventional chromatography-identical acyl groups and R2, R6, X and n proceed the above, such as chromatography on a column with Biorex 70.55 meanings, but also R2 Hydroxymethyl is a weakly acidic polyacrylic acid resin, purified. Occasionally can.

only minor impurities are removed by this chromatography. The acylation of the compounds of the formula 12A cannot be completely removed. In these cases, however, even using only a small excess, basic contaminants become effective by passing through a i.e. from approx. 1.0 to 1.2 molar equivalents, an acylanhy column with Dowex 50 (H +), a sul-6o drides crosslinked with divinylbenzene, acylchlorides, acylcyanides or acylimidazolides in formulated polystyrene resin, or removed by chromatography-inert organic solvent containing a tertiary phie over a column of Amberlite XAD-2, one with 2% divinyl base, as outlined above, with a selective benzene crosslinked polystyrene, in water or aqueous metha-acylation of the primary 6-hydroxyl group . These noi are all partially unblocked glycopeptides. The reaction is preferably separated by the gradual addition of. 65 acylating agent to a solution of a compound of the form

A further embodiment of the invention relates to 12A carried out at approximately 0 to approximately 20 ° C. and is monitored by the synthesis of 4,6-di-O-acyl derivatives of glycodipep thin-layer chromatography until the starting material of the formula 13 wherein R and R1 the same or different material is essentially consumed. According to a conventional

636 887 10

The 6-O-acyl derivatives of the formula are worked up using the compounds of the formula 12D using Acy-12F, in which R3 denotes an acyl group which is the same as R and the detergent defined by carboxylic acids of the formula R4OH-R1 and X1 , n, R2 and R6 have the above meanings, under the conditions set forth for the preparation of the compounds shown by chromatography over a suitable adsor formula 12E or 12C. The resultie-bens, such as silica, or isolated by crystallization and 5 renden products of formula 12E, wherein the acyl residues R4 and purified. The catalytic hydrogenolysis of the compounds R5 are either the same or different and correspond to the above definitions of the formula 12F as described above with uses and R2, R6, X1 and n have the above meaning of a catalyst derived from palladium and have resulted , can be isolated by conventional methods, compounds of the formula 13, in which R and R2CO acyl residues and are purified.

of the type defined above, but with benzyloxyacetyl 10. The compounds of the formula 12E can also be replaced by a hydroxyacetyl group (glycolyl group). tere acylation of compounds of the formula 12F with Ver- and R1 is hydrogen. Expression of acylating agents derived from acids of the formula

In order to selectively introduce an acyl group into the 4-O-position- R5OH derived as described above, it is necessary to first selectively become a protecting group on the turn. Again, the resulting compounds of the For-6-hydroxyl group of the compound of formula 12A to be introduced with 12E, in which the acyl groups R4 and R5 are either the same. This can expediently be carried out using one or different and corresponding to the above definitions of trityl ether or substituted trityl ether, ie one in which chen and R2, R6, X1 and n have the above meanings, according to the well-known method of carbohydrate chemistry. Conventional methods are thus isolated and purified, the compounds of the formula 12A with triphenylmethyl chloride. The removal of protective groups from the compounds (trityl chloride) or with related reagents, such as anisyldi 20 of the formulas 12D, 12E and 12F, is carried out by catalytic hydrophenylmethyl chloride (methoxytrityl chloride), Dianisylphenyl genolysis using palladium-derived methyl chloride (dimethoxytrityl chloride) or trianisylme catalysts in an acidic medium, as described above for the thylchloride (trimethoxytrityl chloride), in pyridine or in inert conversion of the compounds of the formula 11 into compounds, such as dimethylformamide, dimethyl sulfogen of the formula 13 has been described. The resulting proxy, acetonitrile and the like containing pyridine, products are the compounds of formula 13 wherein R6, X, n and [see e.g. M. Smith et al. J. Amer. Chem. Soc. 84,430 R2CO- have the above meanings and R and R1 are the same

(1962) for the representative application of these reagents]. or mean different acyl groups or one of the sym- In general, the reactions at about 10 to about 50 ° C, bole R and R1 represents hydrogen, while the other means an acyl group advantageously carried out in pyridine at room temperature. In any case, the acyl group will correspond. The reaction time depends on the reagent used R, R1, R6 and R2CO- the above definition, with the exception of genz and varies from about 2 to about 5 hours in that the benzyloxyacetyl group by the hydroxyacetyl

Trianisylmethylchloride until about 3 to about 6 days for the triphenyl group (glycolyl group) is replaced. These compounds of methyl chloride. The resulting 6-O-trityl esters or substitute formula 13 are obtained by precipitation from methanol by addition of 6-O-trityl esters of the formula 12B by conventional or a less polar solvent, such as ethyl acetate, or by methods such as precipitation, crystallization or chromatography Ether, isolated and then further purified by chromatography on Biorex phy over a suitable adsorbent such as silica, light 70 or Amberlite XAD-2, as isolated for the above. In formula 12B, R6, X1, n and R2CO have the transformation of the compounds of formula 11 into the meanings above. fertilize the formula 13 described. It is clear that others

The acylation of the free 4-hydroxyl group of the compound chromatographic methods, which are known to the peptide and glycopeptides of the formula 12B using conventional methods, also for these purifications of various acylating agents, such as acyl chlorides, acyl anhydrides, acyl can be applied.

Cyanides or acylimidazolides, which are derived from acids. Of course, the isolation of the

the rest of which R3 has the meaning given above. If desired, the reaction can be carried out using any suitable compound.

under the separation or purification methods used for the acylation of the compounds of the formula 12A, as is carried out under the conditions described, and results, for example, by extraction, crystallization, thin-layer bonds of the formula 12C, but with the molar ratio of the chromatography, thick-layer chromatography or acid acylating agent possibly only about 1 to about 5 equivalents chromatography or a combination of these process elements. The resulting aeylated products of the ways. Explanations of suitable separation and isolation mel 12C, in which R2, R3, R6, X1 and n proceed the above meanings can be found in the following examples. However, other equivalent separation or graphing over a suitable adsorbent, such as silica, could of course also be used by crystallization, precipitation, or chromatographic techniques.

gated and cleaned. With the expression «room temperature» a temperature

The selective hydrolysis of the trityl group or substitution from approx. 15 to approx. 25 ° C denotes.

trityl group can under defined acidic conditions The following examples illustrate the invention.

be carried out. This is advantageously done by treating 55 with 70% acetic acid at 100 ° C. until a clear solution is obtained, example 1

forms, and then about 2 minutes longer. These conditions can be 50 ml of concentrated sulfuric acid are carefully added to 500 ml in terms of temperature, duration and acid strength ml of anhydrous ether, whereupon the mixture can be varied by 500 by a person skilled in the art, but excessively strong ml of benzyl alcohol is added. The ether will have to be avoided by conditions. If the methoxy-60 vapor is removed in vacuo and the residue is used in the course of trityl derivatives of the formula 12C, those of 30 minutes with 67 g of D-aspartic acid (formula 1, n = 1) are in

Conditions for acidic hydrolysis are much milder, and the multiple portions are mixed. The resulting suspension of 80% acetic acid at room temperature is stirred at 22 ° C. for 16 hours, a clear rend from about 5 minutes to about 5 hours being sufficient. The resulting solution forms. This vigorously stirred solution is mixed with 1 liter of 4-O-acyl derivatives of the formula 12D, in which X1, n, R6, R3 and R2 63 95% ethanol and 250 ml of pyridine. According to some of the above meanings, crystallization is started by minutes, and the mixture is isolated or purified by chromatography on silica. Stored at 0 ° C for hours. The product is isolated by Fil-Die further acylation of the 6-hydroxyl group and washed thoroughly with ether, whereby

11 636 887

77.9 g of a white solid with a melting point of analysis for C16H22N2O5 (322.35):

172 to 177 ° C can be obtained; the solid substance is calculated from 1: C59.61 H6.88 N8.69

Liter of water containing 10 drops of pyridine, recrystallized: C59.81 H 6.80 N 8.87

and gives 44.3 g of D-aspartic acid-β-benzyl ester (formula 2, n provides.

= 1) with a melting point of 220 to 221 ° C and [cc] d s If you use a stoichiometrically equivalent amount of tert. Propyloxycarbonyl-D-glutamic acid y-benzyl ester (formula 3, in the same way, but using a stoichiometric n = 2) instead of tert-butyloxycarbonyl-D-aspartic acid-β-trically equivalent amount of D-glutamic acid (formula 1, n = 2) benzyl ester used, 1.92 g of d-spartic acid are obtained in the same way, 56.3 g of D-glutamine-zyl-tert-butyloxycarbonyl-D-isoglutaminate (formula 4, n = 2) acid-y -benzyl ester (formula 2, n = 2) with a melting point 10 with a melting point of 125 to 126 ° C; [a2-2.6 ° (13.3 of 161 is 162 ° C and [a] o -19.3 ° (6 mg / ml, acetic acid). mg / ml, dimethylformamide).

Example 4

eispie. A. 2.95 g of benzyl tert-butyloxycarbonyl-D-isoglutaminate

250 ml of anhydrous] 5 (formula 4 n = 2) with 14 ml of a saturated solution are placed in a 500 ml round-bottomed flask

Dimethyl sulfoxide 1 15 g of D-aspartic acid-β-benzyl ester VQn hydrogen chloride in ethyl acetate. The reaction mixture (formula 2, n = 1), 13.5 ml of methylamine and 9 ml of tert-butyl azimix is kept for 1Q minutes at 22 ° C. and then added with doformate, whereupon the resulting solution is mixed with 42 hours of 80 ml of ether to mail out the product that is kept by the lang at 22C. The reaction mixture is isolated by centrifugation and carefully dried in vacuo, then it is poured into 700 ml of water and the mixture is extracted three times with ^ 2, extracting 2 33 Y.Benzyl-D-isoglutaminate hydrochloride with 200 ml of ether. The aqueous layer is obtained in ice (formula 52) which is cooled in stage B without further purification, 200 ml of ethyl acetate are added and the aqueous phase of this egg is used.

brought to pH = 2.8 by adding citric acid. The B A solution of 201 g of tert-butyloxycarbonyl-L-alanine

Layers are separated, whereupon the aqueous phase is extracted further (Formd 6 x, = L_Ala l) with 10 ml of dry dimethylforma three times with 200 ml of ethyl acetate. The combined a mid is mk j-hydroxybenzotriazole and 2.19 g of dicyclo-organic phases are successively five times with 200 ml of hexylcarbodiimide. The resuiting mixture is 90 minutes, then extracted with 200 ml of saturated sodium chloride solution for minutes, kept at 22 oC and then dried in a solution and then over magnesium sulfate. The Athy-ßenzyl-D-isoglutaminate hydrochloride (Formula 5, n = 2)

Laceta solution is filtered and the filtrate is dry and ml diisopro yläth lamin in 10 ml dimethylformamide

RU? H! e / f'n r T ■ lì 30 filtered. The insoluble cake obtained in this filtration is crystallized from a mixture of ethyl acetate and hexane • * • ici rv i * -aucj ii n * * r> * 1 t_ 1 i ~ * v ni 1 is washed twice with 5 ml of dimethylformamide, followed by and l3,2gtert-butyloxycarbonyl-D-aspartic acid-ß-benzyle- .. • ia _ ü i • u V. / -c i -> i \ • 0 u 1 1 * the washing liquids are added to the reaction mixture (formula 3, n = 1) with a melting point of 102 to -, ... 1C * j i ru u 4 • j r-.

lAion r i25. müo / u / 1 * i_ ir -jx which is kept at 22 C for 1 hour. The

103 ° C; [<x] d> + 19.4 ° (14mg / ml, dimethylformamide); t> i ^ • t, • a • enn i wt j j-

a t c »r * TT x a, ->% -> -> À \ reaction mixture is poured into 500 ml water and the

Analysis for C. ^ NO, (323 34): 35 resulting solution twice with 250 ml of ethyl acetate

e ^ "„ '^ H,' Q XT, '~ R hiert. The combined organic phases are successively

®e '"' '' four times with 200 ml water, three times with 150 ml 5% aqueous

. .... potassium bicarbonate solution and with 150 ml of saturated cooking

If you wash a stochiometric / equivalent amount of saline. The ethyl acetate solution is then dried over D-glutamic acid y-benzyl ester (formula 2, n = 2) instead of 4o magnesium sulfate, filtered and dried to dryness.

D-Aspartic acid-ß-benzy ester is used to obtain in the same way fti, whereby a solid residue is obtained, which is crystallized from a mixture of ethanol and ether with 16 9g tert-butyloxcycarobnyl-D-glutamic acid and y-benzyl ester (Formula 3, n = 2) as a pale yellow oil that is sufficiently pure 2 2 benzyl-tert-butyloxycarbonyl-L-alanyl-D-isoglutaminate to be used directly in the next step. (Formd 7, n = 2j X, = L-alanyl) with a melting point of

45 140 to 141 ° C; [a] D20 ° (7.6 mg / ml, dimethylformamide);

Example 3 Analysis for C20H29N3O6 (407.45):

A solution of 3.23 g, stirred with a magnetic stirrer: C58.95 H7.17 N 10.31 tert-butyloxycarbonyl-D-aspartic acid-β-benzyl ester (formula found: C59, II H 6.80 N 10, 50 3, n = 1) and 1.6 ml of triethylamine in 20 ml of tetrahydrofuran.

is cooled to -15 ° C. A solution of 1.55 ml of chlorine-50. If a stoichiometrically equivalent amount of isobutyl formate in 5 ml of tetrahydrofuran is added to tert-butyloxycarbonylglycine,

added to the above solution, whereupon the temperature was tert-butyloxycarbonyl-L-valine,

Is held at -15 ° C for 25 minutes. Then you leave tert-butyloxycarbonyl-L-leucine,

bubble dry ammonia gas into the reaction mixture, tert-butyloxycarbonyl-L-isoleucine,

Maintaining the temperature at -15 ° C for 30 minutes. 55 tert-butyloxycarbonyl-L-a-aminobutyric acid,

Thereafter, the temperature of the reaction mixture is left in tert-butyloxycarbonyl-O-benzyl-L-serine,

Rise over a period of 15 minutes to 0 ° C., whereupon the conductance tert-butyloxycarbonyl-O-benzyl-L-threonine,

ammonia. The tetrahydrofuran tert-butyloxycarbonyl-L-methionine,

is evaporated in vacuo and the residue between 80 ml of tert-butyloxycarbonyl-S-benzyl-L-cysteine,

Distributed water and 200 ml of ethyl acetate. The ethyl acetate layer 60 tert-butyloxycarbonyl-L-phenylalanine,

is successively twice with 50 ml of 5% aqueous tert-butyloxycarbonyl-O-benzyl-L-tyrosine,

Sodium bicarbonate and tert-butyloxycarbonyl-L-tryptophan with 50 ml of saturated saline,

washed and then dried over magnesium sulfate. The filter tert-butyloxycarbonyl-e-carbobenzyloxy-L-lysine,

trated solution is evaporated to dryness and gives 3.22 g of tert-butyloxycarbonyl-y-carbobenzyloxy-L-ornithine,

a solid substance which recrystallizes from 50 ml of ethyl acetate 65 tert-butyloxycarbonyl-gu-nitro-L-arginine,

and 2.72 g of benzyl tert-butyloxycarbonyl-D-isoaspartate tert-butyloxycarobnyl-NIm-benzyl-L-histidine,

(Formula 4, n = 1) with a melting point of 159 to 169 ° C; y-benzyl-tert-butyloxycarbonyl-L-glutamate,

[a] o + 17.0 ° (10 mg / ml, dimethylformamide); tert-butyloxycarbonyl-L-glutamine,

636 887

12

ß-benzyl-tert-butyloxycarbonyl-L-aspartate, tert-butyloxycarbonyl-L-asparagine, tert-butyloxycarobnyl-L-proline and tert-butyloxycarbonyl-O-benzyl-L-hydroxypyroline used instead of tert-butyloxycarbonyl-L-alanine, this gives the corresponding protected dipeptide derivatives (benzyl esters), namely

Benzyl tert-butyloxycarbonylglycyl-D-isoglutaminate with a melting point of 113 to 114 ° C; [a] o + 0.7 ° (7 mg / ml, dimethylformamide);

Analysis for C19H27N3O6 (393.45): »

calc .: C 58.00 H 6.92 N 10.68 found: C 58.00 H 7.20 N 10.67

Benzyl tert-butyloxycarbonyl-L-valyl-D-isoglutaminate with a melting point of 152 to 153 ° C.; [a] o + 9.1 ° (10 mg / ml, dimethylformamide);

Analysis for C22H33N3O6 (435.50):

calc .: C 60.67 H 7.64 N9.65 found: C 60.88 H 7.90 N9.67

Benzyl tert-butyloxycarbonyl-L-leucyl-D-isoglutaminate with a melting point of 105 to 106 ° C; [a] o -3.4 ° (10 mg / ml, dimethylformamide);

Analysis for C46H52N4O11 (836.95):

calc .: C 66.01 H 6.26 N6.69 found: C 65.79 H 6.24 N6.52

Benzyl tert-butyloxycarbonyl-L-isoleucyl-D-isoglutaminate; Benzyl tert-butyloxycarbonyl-L-a-aminobutyryl-D-isoglutaminate with a melting point of 102 to 104 ° C; [oc] d5 + 3.1 ° (10 mg / ml, dimethylformamide);

Analysis for C21H31N3O6 (421.50):

calc .: C 59.84 H 7.41 N9.97 found : C 59.60 H 7.56 N 10.00

Benzyl-tert-butyloxycarbonyl-O-benzyl-L-seryl-D-isoglutaminate with a melting point of 64 to 66 ° C; [a] o4 + 1.0 ° (8.2 mg / ml, dimethylformamide);

Analysis for C27H35N3O7 (513.57):

calc .: C 63.14 H 6.87 N8.18 found: C 63.41 H 6.92 N8.29

Benzyl tert-butyloxycarbonyl-O-benzyl-L-threonyl-D-iso-glutaminate with a melting point of 117 to 120 ° C [a] o + 7.1 ° (5.0 mg / ml, dimethylformamide);

Analysis for C28H37N3O7 (527.63):

Calc .: C 63.74 H 7.07 N7.96 Found: C 63.59 H 6.81 N7.84

Benzyl tert-butyloxycarbonyl-L-methionyl-D-isoglutaminate with a melting point of 114 to 115 ° C; [cc] d5 + 25 ° (10 mg / ml, dimethylformamide);

Analysis for C22H33N3O6S (467.59):

calc .: C 56.51 H 7.11 N8.99 found: C 56.59 H 7.24 N8.93

Benzyl tert-butyloxycarbonyl-S-benzyl-L-cysteinyl-D-iso-glutaminate,

Benzyl tert-butyloxycarbonyl-L-phenylalanyl-D-isoglutamate with a melting point of 139 to 140 ° C; [a] o -10.7 ° (10 mg / ml, dimethylformamide);

Analysis for C26H33N3O6 (483.57):

calc .: C 64.58 H 6.88 N8.69 found: C 64.62 H 7.17 N8.68 '

Benzyl tert-butyloxycarbonyl-O-benzyl-L-tyrosyl-D-isogluaminate with a melting point of 172 to 173 ° C; [a] o4 + 4.2 ° (4.6 mg / ml, dimethylformamide);

Analysis for C33H39N3O7 (589.66);

calc .: C 67.21 H 6.67 N7.13 found : C 67.44 H 6.88 N7.06

Benzyl-tert-butyloxycarbonyl-L-tryptophanyl-D-isoglutami-

nat,

Benzyl tert-butyloxycarbonyl-e-carbobenzyloxy-L-lysyl-D-isoglutaminate with a melting point of 94 to 97 ° C; [a] o5 -3.5 ° (8 mg / ml, dimethylformamide);

Analysis for C31H42N4O8 (598.68):

calc .: C62.19 H 7.07 N9.36 found: C 62.19 H 7.03 N9.44

Benzyl-tert-butyloxycarbonyl-ô-carbobenzyloxy-L-orniethyl-D-isoglutaminate,

Benzyl-tert-butyloxycarbonyl-gu-nitro-L-arginyl-D-isoglutaminate,

Benzyl-tert-butyloxycarbonyI-NIm-benzyl-L-histidyl-D-iso-glutaminate,

Benzyl-tert-butyloxycarbonyl-y-benzyl-L-glutamyl-D-iso-glutaminate,

Benzyl-tert-butyloxycarbonyl-L-glutaminyl-D-isoglutami-

nat,

Benzyl-tert-butyloxycarbonyl-β-benzyl-L-asparagyl-D-iso-glutaminate,

Benzyl-tert-butyloxycarbonyl-L-asparaginyl-D-isoglutami-

nat,

Benzyl tert-butyloxycarbonyl-L-prolyl-D-isoglutaminate, a colorless oil with [a] è4 -9.0 ° (14.4 mg / ml, dimethylformamide); Analysis for C22H31N3O6 (433.49);

calc .: C 60.95 H 7.21 N9.69 found : C 61.06 H 7.49 N9.85

and benzyl-tert-butyloxycarbonyl-O-benzyl-L-hydroxypro-lyl-D-isoglutaminate as an oil with [aß5 -2.4 ° (5 mg / ml, dimethylformamide).

If a stoichiometrically equivalent amount of benzyl-tert-butyloxycarbonyl-D-isoasparticulate hydrochloride (formula 4, n = 1) is used instead of benzyl-tert-butyloxycarbonyl-D-isoglutaminate hydrochloride (formula 4, n = 2), the corresponding protected dipeptide derivatives (benzyl esters) are obtained in the same way, namely

Benzyl tert-butyloxycarbonylglycyl-D-iso-aspartate, benzyl-tert-butyloxycarbonyl-L-alanyl-D-iso-aspartate with a melting point of 126 to 127 ° C; [a] è5 -6.4 ° (10 mg / ml, dimethylformamide);

Analysis for C19H27N3O6 (393.43);

calc .: C 58.00 H 6.92 N 10.68 found : C 57.98 H 7.10 N 10.66

Benzyl-tert-butyloxycarbonyl-L-valyl-D-isoaspartate, benzyl-tert-butyloxycarbonyl-L-leucyl-D-isoaspartate, benzyl tert-butyloxycarbonyl-L-isoleucyl-D-isoaspartate, benzyl-tert-butyloxycarbonyl-La- aminobutyryl-D-isoaspa-raginate,

Benzyl-tert-butyloxycarbonyl-O-benzyl-L-seryl-D-isoasparaginate,

Benzyl-tert-butyloxycarbonyl-O-benzyl-L-threonyl-D-isoa-asparaginate,

Benzyl-tert-butyloxycarbonyl-L-methionyl-D-isoasparagi-

nat,

Benzyl tert-butyloxycarbonyl-S-benzyl-L-cysteinyl-D-isoa-asparaginate,

Benzyl-tert-butyloxycarbonyl-L-phenylalanyl-D-isoasparaginate,

Benzyl-tert-butyloxycarbonyl-O-benzyl-L-tyrosyl-D-isoaspa-raginate,

Benzyl tert-butyloxycarbonyl-L-tryptophanyl-D-isoasparaginate,

Benzyl tert-butyloxycarobnyl-e-carbobenzyloxy-L-lysyl-D-isosparaginate,

Benzyl-tert-butyloxycarbonyl-5-carbobenzyloxy-L-ornithyl-D-isoaspartate,

Benzyl-tert-butyloxycarbonyl-gu-nitro-L-arginyl-D-isoaspa-raginate,

Benzyl-tert-butyloxycarbonyl-NIm-benzyl-L-hystidyl-D-isoa-asparaginate,

Benzyl tert-butyloxycarbonyl-y-benzyl-L-glutamyl-D-isoa-asparaginate,

Benzyl-tert-butyloxycarbonyl-L-glutaminyl-D-isoasparagi-

nat,

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

13

636 887

Benzyl tert-butyloxycarbonyl-β-benzyl-L-asparagyl-D-isoa-asparaginate,

Benzyl-tert-butyloxycarbonyl-L-asparaginyl-D-isoasparagi-

nat,

Benzyl-tert-butyloxycarbonyl-L-propyl-D-isoaspartate and

Benzyl tert-butyloxycarbonyl-O-benzyl-L-hydroxyprolyl-D-isoasparticate.

Example 5

A. A solution of 3.57 g of benzyl-2-amino-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside (Formula 8A) and 2.49 g of benzoic anhydride in 200 ml of methanol is for 45 minutes heated to reflux. The resulting mixture is allowed to cool to 22 ° C. and the crystalline solid is isolated by filtration, washed with methanol and recrystallized from hot methanol, giving 3.46 g of benzyl-2-benza-mido-4,6-0- benzylidene-2-deoxy-aD-glucopyranoside (Formula 8B, R2 = Ph) with a melting point of 218 to 220 ° C; [a5 + 119 ° (10 mg / ml, pyridine);

Analysis for CîtHîiNOs-HîO (479.54);

calc .: C 67.63 H 6.10 N2.92 found : C 68.09 H 5.81 N2.87.

B. A solution of 3.57 g of benzyl-2-amino-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside (formula 8A) and 2.31 g of tri-fluoroacetic anhydride in 100 ml of tetrahydrofuran is 1 hour heated to reflux for a long time. The resulting solution is allowed to cool to about room temperature and then added to 1 liter of ice water. The precipitated solid is isolated by filtration, washed thoroughly with water and dried in vacuo to give 4.51 g of benzyl-4,6-0-benzylidene-2-deoxy-2-trifluoroacetamido-aD-glycopyranoside with a melting point of 242 to 243 ° C; [a5 + 115.2 ° (9 mg / ml, dimethylformamide);

Analysis for C22H22NO6F3 • H2O (471.44);

calc .: C56.05 H5.13 N2.97 found: C 56.43 H 5.18 N3.07

C. A solution of 5.4 g benzyl-2-amino-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside (Formula 8A) and 2.7 g methoxy-acetic anhydride in 250 ml methanol is for 30 minutes heated to reflux. The resulting solution is then concentrated in vacuo and the residue is triturated with 150 ml of ether, after filtration 5.99 g of benzyl-4,6-0-benzylidene-2-deoxy-2-methoxyacetamido-aD-glucopyranoside (formula 8B, R2 = -CH2OCH3) with a melting point of 198 to 199 ° C; [a] p + 82.0 ° (10 mg / ml, chloroform);

Analysis for C23H27NO7 (429.47);

calc .: C 64.32 H 6.34 N3.26 found: C 64.19 H 6.28 N3.06 obtained.

If a stoichiometrically equivalent amount of the corresponding acylating agent is used instead of benzoic anhydride and, depending on the physical properties of the product, the modified process B or C is used, the corresponding 2-acylamino-glucose derivatives of the formula 8B are obtained in the same way:

Benzyl-2-formamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-propionamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-butyramido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-valeramido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside with a melting point of 202 to 204 ° C; [a5 + 108.2 ° (10 mg / ml, dimethylformamide);

Analysis for C26H33N06.0.5 HaO (464.57):

calc .: C 76.22 H 7.38 N3.02 found: C 67.65 H 7.36 N3.10

Benzyl-2-heptanamido-4,6-0-benzylidene-2-deoxy-a-D-glu-copyranoside,

Benzyl-2-caprylamido-4,6-0-benzylidene-2-deoxy-a-D-glu copyranoside,

Benzyl-2-nonanamido-4,6-0-benzylidene-2-deoxy-a-D-glu-copyranoside,

Benzyl-2-capramido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-lauramido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-myristamido-4,6-0-benzylidene-2-deoxy-a-D-glu-copyranoside with a melting point of 182 to 184 ° C; [a5 + 55.5 ° (5 mg / ml, chloroform);

Analysis for C34H49N06-0.5 H2O (576.78):

calc .: C 70.80 H 8.74 N2.43 found: C 70.50 H 8.61 N2.53

Benzyl-2-palmitamido-4,6-0-benzylidene-2-deoxy-a-D-glu-copyranoside,

Benzyl-2-stearamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside,

Benzyl-2-arachidamido-4,6-0-benzylidene-2-deoxy-a-D-glu-copyranoside,

Benzyl-2-behenamido-4,6-0-benzylidene-2-deoxy-a-D-glu-copyranoside,

Benzyl-2-benzyloxyacetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside with a melting point of 168 to 169 ° C; [a5 + 72.1 ° (5 mg / ml, chloroform);

Analysis for C29H31NO7 (505.55):

calc .: C68.89 H6.18 N2.77 found: C 68.82 H 6.03 N 2.90 and

Benzyl-2-phenylacetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside.

Example 6

A solution of 41.7 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside (formula 8) in 500 ml of dry dimethylformamide is added in portions with 19.2 g of a 50% solution Dispersion of sodium hydride in oil added. The resulting mixture is stirred at 22 ° C for 30 minutes, 23.3 g of sodium chloroacetate are added and the reaction mixture is heated to 75 ° C for 1 hour. The reaction mixture is cooled in an ice water bath, 125 ml of ethanol are added dropwise until the foaming subsides (about 30 minutes), and the resulting solution is evaporated to dryness in vacuo. The residue thus obtained is mechanically stirred with a mixture of 500 ml of chloroform and 500 ml of water until the sodium salt of the product crystallizes. The crystals are isolated by filtration, resuspended in 3 liters of chloroform, and approximately 450 ml of Dowex 50 (H +) (sulphonated polystyrene resin cross-linked with divinylbenzene) are added, and the mixture is stirred at 22 ° C. for 1 hour. The resin is removed by filtration, the chloroform filtrate dried over magnesium sulfate, filtered again and evaporated to dryness in vacuo, 39 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0-carboxymethyl- aD-glucopyranoside (formula 9, R2 = methyl) with a melting point of 215 to 216 ° C.

If a stoichiometrically equivalent amount of the various compounds obtained in Example 5 is used instead of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyra-noside, the corresponding compounds of the formula are obtained in the same way 9, of which the following are representative examples:

Benzyl-2-benzyloxyacetamido-4,6-0-benzylidene-2-deoxy-3-O-carboxymethyl-a-D-glucopyranoside with an enamel5

10th

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point from 172 to 173 ° C; [a] D + 81.4 ° (5 mg / ml, chloroform); Analysis for C32H35NO7 (577.61):

calc .: C66.06 H 5.90 N2.49 found: C66.17 H 5.96 N2.58

Benzyl-2-methoxyacetamido-4,6-0-benzylidene-2-deoxy-3-O-carboxymethyl-aD-glucopyranoside with a melting point of 209 to 210 ° C; [<x] d + 88.1 ° (10 mg / ml, methanol); Analysis for C25H29NO9 (487.52):

calc .: C 61.59 H 6.00 N2.87 found: C 61.40 H 6.40 N2.77

Benzyl-2-benzamido-4,6-0-benzylidene-2-deoxy-3-0-carboxymethyl-aD-glucopyranoside with a melting point of 257 to 258 ° C; [cc] d + 121.8 ° (10 mg / ml, dimethylformamide); Analysis for C20H29NO8 (519.56):

calc .: C 67.04 H 5.63 N2.70 found: C 67.23 H 5.36 N2.73

Benzyl-2-trifluoroacetamido-4,6-0-benzylidene-2-deoxy-3-0-carboxymethyl-a-D-glucopyranoside,

Benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-3-0-carboxymethyl-aD-glucopyranoside with a melting point of 217 to 218 ° C; [oc] d5 + 106.1 ° (5th mg / ml, chloroform);

Analysis for C28H35NO8 (513.60):

calc .: C65.48 H 6.87 N2.73 found: C 65.06 H 6.74 N2.75

and benzyl-2-myristamido-4,6-0-benzylidene-2-deoxy-3-0-carboxymethyl-a-D-glucopyranoside with a melting point of 188 to 190 ° C.

Example 6 '

A solution of 41.7 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside (formula 8) in 500 ml of dry dimethylformamide is added in portions with 9.6 g of 100% Sodium hydride (crystalline) was added, whereupon the resulting mixture was stirred at 22 ° C. for 30 minutes to give the sodium derivative of the compound of formula 8. Meanwhile, 7.0 g of 100% sodium hydride is carefully added to an ice-cooled solution of 26 g of D, L-2-chloropropionic acid (or a stoichiometrically equivalent amount of D, L-2-bromopropionic acid) in 200 ml of dry dimethylformamide. The resulting mixture is then added to the above sodium derivative and the reaction mixture is stirred at 75 ° C for 3 hours. The reaction mixture is cooled to about 5 ° C. in an ice bath and then mixed with 100 ml of water over a period of 2 hours and then with 100 ml of dimethyl sulfate. The temperature of the reaction mixture is allowed to rise to 22 ° C. and the mixture is then stirred at 22 ° C. for 16 hours, after which it is poured into a large excess of water. The resulting precipitate is isolated by filtration, washed with water, then dissolved in 500 ml of chloroform and the aqueous layer removed. The chloroform solution is dried over magnesium sulfate and then concentrated in vacuo to give 49.6 g of crude ester (Formula 9, R2 = R6 = R7 = methyl). This mixture is chromatographed on a column with 1 kg of silica, which is prepared and eluted with a mixture of ethyl acetate and chloroform (1: 1). The corresponding fractions are combined and evaporated to dryness and give 26.6 g of benzyl-2-acetamido-4,6-0-ben-zyliden-2-deoxy-3-0- (Dl-carbomethoxyethyl) -aD-glucopyra-noside (Formula 9, R2 = R6 = R7 = methyl), which is recrystallized from methanol and has a melting point of 212 to 214 ° C and [aß5 + 126.8 ° (10 mg / ml in chloroform).

A suspension of 26.6 g benzyl-2-acetamido-4,6-0-ben-cylidene-2-deoxy-3-0- (Dl-carbomethoxyethyl) -aD-glucopyra-noside (formula 9, R2 = R6 = R7 = methyl) in 1 liter of methanol is mixed with a solution of 20 g of sodium hydroxide in 1 liter of water, whereupon the mixture is heated to 100 ° C. for 90 minutes and then cooled to room temperature. The resulting solution is concentrated in vacuo to a volume of approximately 500 ml and this solution is then treated with 6-normal hydrochloric acid until the pH is 2.5. The resulting white solid is isolated by filtration, washed thoroughly with water, dried in vacuo over phosphorus pentoxide and then crystallized from methanol to give 21.9 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy -3-0- (Dl-carboxyethyl) -aD-glucopyranoside (formula 9, R2 = R6 = methyl, R7 = hydrogen) with a melting point of 239 to 241 ° C.

10 If a stoichiometrically equivalent amount of other D, L-2-haloalkanoic acids with 4 to 6 carbon atoms is used instead of D, L-2-chloropropionic acid, the compounds (benzyl esters) of the formula 9 in which R6 is alkyl with 2 up to 4 carbon atoms and R7 15 = hydrogen; representative examples of these compounds are:

Benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (Dl-carboxy-l-propyl) -aD-glucopyranoside with a melting point of 216 to 217 ° C; [cx] d + 126.7 ° (5 mg / ml, dimethyl-20 formamide);

Analysis for C26H31NO8 (485.55):

calc .: C 64.32 H 6.44 N2.88;

found: C 64.56 H 6.22 N2.98

and benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (D-25 l-carboxy-l-pentyl) -a-D-glucopyranoside with a melting point of 232 to 233 ° C; [a5 + 113.2 ° (5 mg / ml, dimethylformamide);

Analysis for C28H35NO8 (513.60):

calc .: C 65.48 H 6.87 N2.73 30 found: C 65.68 H 7.02 N2.77.

If a stoichiometrically equivalent amount of the various compounds obtained in Example 5 is used instead of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyra-noside, the corresponding-35 den are obtained in the same way Compounds of formula 9; representative examples are: Benzyl-2-benzyloxyacetamido-4,6-0-benzylidene-2-deoxy-3-0- (Dl-carboxyethyl) -aD-glucopyranoside with a melting point of 220 to 221 ° C; [aß5 +76, 8 ° (5 mg / ml, chloroform); Analysis for C32H35NO9 (577.61):

40 calc .: C 66.54 H 6.11 N2.43: C 66.48 H 6.37 N2.46;

Benzyl-2-methoxyacetamido-4,6-0-benzylidene-2-deoxy-3-0- (D-1-carboxyethyl) -a-D-glucopyranoside with a melting point of 209 to 210 ° C; [a5 + 107 ° (3 mg / ml, methanol); 45 Analysis for C26H31NO9 (501.55):

calc .: C 62.27 H 6.23 N2.79 found: C 63.00 H 6.24 N2.78

Benzyl-2-benzamido-4,6-0-benzylidene-2-deoxy-3-0- (D-l-carboxyethyl) -a-D-glucopyranoside with a melting point 50 of 275 to 276 ° C; [a5 + 114.7 ° (5 mg / ml, dimethylformamide);

Analysis for CsoHsiNOs (533.59):

calc .: C 67.53 H 5.86 N2.63 found: C 67.36 H 5.94 N2.54 55 benzyl-2-trifluoroacetamido-4,6-0-benzylidene-2-deoxy-3-0 - (D-1-carboxyethyl) -aD-glucopyranoside,

Benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-3-0- (Dl-carboxyethyl) -aD-glucopyranoside with a melting point of 234 to 236 ° C; [aßs + 117.2 ° (5th mg / ml, dimethylforma-6omide);

Analysis for C29H37NO8 (527.62):

calc .: C 66.02 H 7.07 N2.65 found: C 66.01 H 6.88 N2.69;

65 and benzyl-2-myristamido-4,6-0-benzylidene-2-deoxy-3-0- (D-1-carboxyethyl) -a-D-glucopyranoside with a melting point of 177 to 178 ° C; [a5 + 95.5 ° (5 mg / ml, dimethylformamide);

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Analysis for C37H53NO8 (639.84):

calc .: C 69.46 H 8.35 N2.19 found: C69.38 H 8.21 N2.16.

Example 6 "

4.17 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside (formula 8) are dissolved in 30 ml of dry pyridine, whereupon the solution is evaporated to dryness in vacuo. This process is repeated and the residue is then dissolved in 75 ml of dry dimethylformamide and 0.72 g of 100% sodium hydride (crystalline) is added in portions; the resulting mixture is stirred at 40 ° C for 1 hour to give the sodium derivative of the compound of formula 8. This solution is then added dropwise over 15 minutes to a vigorously stirred solution of 5.3 g of D, L-2-bromo-decanoic acid methyl ester ( prepared from 5.0 g of D, L-2-bromo-decanoic acid and an ethereal solution containing 31 mmol of diazo-methane) in 25 ml of dimethylformamide. The resulting mixture is stirred at 22 ° C for 16 hours and then evaporated to dryness in vacuo. The resulting residue is then partitioned between 500 ml of ethyl acetate and 250 ml of water. The ethyl acetate phase is washed further with 100 ml of water, dried over magnesium sulfate and then concentrated in vacuo to give 7.7 g of crude ester (formula 9, R2 = R7 = methyl, R6 = n-CsHn). This mixture is chromatographed on a column with 400 g of silica, which is prepared with a mixture of ethyl acetate and chloroform (1: 9) and with a linear gradient of 2 liters of a mixture of ethyl acetate and chloroform (1: 9) to 2 liters a mixture of ethyl acetate and chloroform (3: 7) eluted. The appropriate fractions are combined and evaporated to dryness to give 2.46 g of benzyl-2-aceta-m ido-4,6-0-benzylidene-2-deoxy-3-0- (D-1-carbomethoxy-1-nonyl) ) -aD-glucopyranoside (Formula 9, R2 = R7 = methyl, R6 = n-CsHn) with a melting point of 146 to 148 ° C; [a5 + 89.0 ° (5 mg / ml, chloroform);

Analysis for C33H45NO8 (583.73):

calc .: C 67.90 H 7.77 N2.40 found: C 68.29 H 7.77 N2.44.

A solution of 1.17 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (D-1-carbomethoxy-1-nonyl) -aD-glucopyra-noside (formula 9, R2 = R7 = methyl, R6 = n-CsHn) in 35 ml of warm (about 60 ° C.) methanol, a solution of 0.8 g of sodium hydroxide in 35 ml of water is added dropwise, at such a rate, that no precipitation of the starting material is observed. The resulting solution is heated to reflux for 25 minutes and, after cooling to 22 ° C., brought to pH = 2.5 with 6 normal hydrochloric acid. The resulting mixture is immediately mixed with 250 ml of ice water and the precipitated white solid is isolated by filtration, washed thoroughly with water and then dried in vacuo over phosphorus pentoxide and gives 1.13 g of benzyl-2-acetamido-4,6-0-benzylidene. 2-deoxy-3-0- (Dl-carboxyl-1-nonyl) -aD-glucopyranoside (formula 9, R2 = methyl, R6 = n-CsHn, R7 = hydrogen) with a melting point of 194 to 196 ° C;

[a5 + 94.7 ° (5 mg / ml, dimethylformamide);

Analysis for C32H43NO8 (569.70):

calc .: C 67.47 H 7.61 N2.46 found: C 67.39 H 7.62 N2.55.

If a stoichiometric equivalent amount of another D, L-2-bromoalkanoic acid methyl ester with 5 to 18 carbon atoms is used instead of D, L-2-bromo-decanoic acid methyl ester, the compounds of the formula 9 in which R6 is alkyl with 5 to 18 carbon atoms are obtained in the same way means and R7 = hydrogen; are representative examples of these compounds

Benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (D-l-

carboxy-l-tridecyl) -a-D-glucopyranoside with a melting point of 157 to 159 ° C; [a5 + 77.2 ° (5 mg / ml, dimethylformamide) and

Benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (Dl-carboxy-l-heptadecyl) -aD-glucopyranoside with a melting point of 155 to 158 ° C; [aß5 + 81, 4 ° (5 mg / ml, dimethylformamide).

If a stoichiometrically equivalent amount of the various compounds obtained in Example 5 is used instead of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside, the corresponding compounds of the formula are obtained in the same way 9.

Example 7

A. 0.44 g of benzyl tert-butyloxycarbonyl-L-valyl-D-isoglutaminate (formula 7, n = 2, X1 = L-valyl) are at 22 ° C. with 5 ml of a saturated solution of hydrogen chloride in ethyl acetate transferred. After 20 minutes, 40 ml of ether are added, the precipitated salt is isolated by centrifugation and carefully dried in vacuo, giving benzyl-L-valyl-D-isoglutaminate hydrochloride (formula 10, n = 2, X1 = L-valyl) becomes.

B. A solution of the above benzyl-L-valyl-D-isoglutaminate hydrochloride (formula 10, n = 2, X1 = L-valyl) in 5 ml of dimethylformamide is mixed with 0.17 ml of diisopropylethylamine and then with a solution of 0.139 g Diisopropylcarbodiimide, 0.178 g of 1-hydroxybenzotriazole and 0.512 g of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (D-1-carboxyethyl) -aD-glucopyranoside (formula 9, R2 = R6 = methyl, R7 = hydrogen) in 5 ml of dimethylformamide. The resulting reaction mixture is stirred at 22 ° C. with a magnetic stirrer and the reaction is monitored by the Kaisertest, further amounts of the reagents being added until the reaction is complete. After the reaction has ended, the reaction mixture is poured into an excess of water and the resulting solid is isolated by filtration, washed thoroughly with water and then twice with ethanol and dried in vacuo over phosphorus pentoxide to give 0.74 g of benzyl-2- (benzyl-2 -acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate (formula 11, n = 2, X1 = L-valyl , R2 = R6 = methyl) with a melting point of 275 to 277 ° C (decomposition); [a5 + 76.0 ° (10 mg / ml in methanol: chloroform, 15:85);

Analysis for C41H50N.O11 (774.84):

calc .: C 63.55 H 6.50 N7.23 found: C 63.45 H 6.51 N7.06.

If a stoichiometrically equivalent amount of the various products of Example 4 is used instead of benzyl tert-butyloxycarbonyl-L-valyl-D-isoglutaminate, the corresponding protected glycopeptide derivatives (benzyl esters) are obtained in the same way:

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-glycyl-D-isoglutaminate with a melting point of 252 to 253 ° C; [a5 + 80.6 ° (2.1 mg / ml, dimethylformamide);

Analysis for C38H44N4O11 (732.80):

calc .: C 62.28 H 6.05 N7.65 found: C 62.03 H 6.27 N7.53

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-alanyl-D-isoglutaminate with a melting point of 238 to 239 ° C; [a5 + 88.9 ° (6 mg / ml, dimethylformamide);

Analysis for C40H48N4O11 (760.86):

calc .: C 63.14 H 6.36 N7.36 found: C 62.93 H 6.07 N7.31

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) propionyl-L-leucyl-D-isoglutaminate with a melting point of 248 to 250 ° C; [a3 + 89.4 ° (6 mg / ml in dimethylformamide);

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Analysis for C43H54N4O11 (802.94):

calc .: C 64.32 H 6.78 N6.98 found: C 64.38 H 6.98 N6.91

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-isoleucyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-la-aminobutyryl-D-isoglutaminate with a melting point of 241 up to 262 ° C; Md + 95.4 ° (10 mg / ml, dimethylformamide);

Analysis for C41H50N4O11 (774.88):

calc .: C 63.55 H 6.50 N7.23 found: C 63.66 H 6.48 N7.23

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-seryl-D-iso- glutaminate with a melting point of 268 to 269 ° C; [oc] d + 19.1 ° (2.3 mg / ml, dimethylformamide);

Analysis for C47H54N4O12 (866.98):

calc .: € 65.11 H 6.28 N6.46 found: C 65.21 H 6.20 N6.47

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-threonyl-D-isoglutaminate with a melting point of 220 to 225 ° C; [a] nS + 76.6 ° (3 mg / ml, dimethylformamide);

Analysis for C4sH56N40i2 (881.01):

calc .: C 65.44 H 6.41 N6.36 found: C 65.78 H 6.82 N6.68

Benzyl 2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-methionyl-D-isoglutaminate with a melting point from 256 to 258 ° C (decomposition); [a] o + 79.8 ° (5 mg / ml, dimethylformamide);

Analysis for C42H52N4O11S (820.98):

calc .: C 61.45 H 6.39 N6.82 found: C 61.38 H 6.38 N6.72

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-S-benzyl-L-cysteinyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-phenylalanyl-D-iso-glutaminate with a melting point from 273 to 277 ° C; [<x] d + 98.9 ° (4.5 mg / ml in dimethylformamide);

Analysis for C46H52N4O11 (836.95):

calc .: C 66.01 H 6.26 N6.69 found: C 66.29 H 6.27 N6.49

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-tyrosyl-D-isoglutaminate with a melting point of 276 ° C (decomposition); [a4 + 85.4 ° (2.5 mg / ml, dimethylformamide);

Analysis for C53H58N4O12 (943.08):

calc .: C 67.50 H 6.20 N5.94 found: C 67.49 H 6.16 N5.77

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-tryptophanyl-D-iso-glutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-e-carbobenzyloxy-L-lysyl-D-isoglutaminate with a melting point of 253 to 259 ° C (decomposition); [a] o + 79.2 ° (10 mg / ml, dimethylformamide);

Analysis for CsiHóiNsOu (952.08):

calc .: C 64.34 H 6.46 N7.36 found: C 64.07 H 6.72 N7.31

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-8-carbobenzyloxy-L-ornithyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-gu-nitro-L-arginyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-NIm-benzyl-L-histidyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-y-benzyl-L-glutamyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-glutaminyl-D-isogluaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-ß-benzyl-L-asparagyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-asparaginyl-D-isogluaminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamate with a melting point from 179 to 180 ° C; [<x] d4 + 98.2 ° (3 mg / ml, dimethylformamide);

Analysis for C42H50N4OU (786.89):

calc .: C64.ll H 6.40 N7.12 found: C 64.36 H 6.29 N7.01

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-hydroxypro-lyl-D- isoglutaminate with a melting point of 75 to 79 ° C; Md + 93.5 ° (10 mg / ml, dimethylformamide);

Analysis for C49H56N4O12 (893.02):

calc .: C 65.90 H 6.32 N6.27 found: C 65.71 H6.55 N6.17

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-glycyl-D-iso-aspartate, benzyl-2- (benzyl -2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoaspartate with a melting point of 226 to 228 ° C ; [a] o5 +107.1 ° (10 mg / ml, dimethylformamide);

Analysis for C39H46N4O11 (746.83):

calc .: C 62.72 H 6.21 N7.50 found : C 62.78 H 6.11 N7.04

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-iosoasparagi-nate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-leucyl-D-isoaspartate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-isoleucyl-D-isoasparaginate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-a-aminobutyryl-D-iso-aspartate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-seryl-D-iso-aspartate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-threonyl-D-iso-aspartate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a - D-glucopyranosid-3-0-yl) -D-propionyl-L-methionyl-D-iso-aspartate ,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-S-benzyl-L-cysteinyl-D-iso-aspartate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a - D-glucopyranosid-3-0-yl) -D-propionyl-L-phenylalanyl-D-iso-aspartate ,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-0-benzyl-L-tyrosinyl-D-iso-aspartate,

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Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a - D -glucopyranosid-3-0-yl) -D-propionyl-L-tryptophanyl-D-iso- D-glucopyranosid-3-0-yl) -acetyl-L-isoleucyl-D-isoglutaminate, aspartate, benzyl- (benzyl- 2-acetamido-4,6-0-benzylidene-2-deoxy-a-

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-la-aminobutyryl-D-isogluta-D-glucopyranoside- 3-0-yI) -D-propionyl-e-carbobenzyloxy-L- 5 minutes with a melting point of 218 to 230 ° C; [a5 + 81.8 ° lysyl-D-isoaspartate, (10 mg / ml, dimethylformamide);

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a analysis for C40H48N4O11 (760.86): D-glucopyranosid-3-0-yl) -D-propionyl-8 -carbobenzyloxy-L- calc .: C63.14 H 6.36 N7.36 ornithyl-D-isoaspartate, found: C62.94 H 6.29 N7.31

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-10 Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside -3-0-yl) -D-propionyl-gu-nitro-L-arginyl-D-D-glucopyranosid-3-0-yl) -acetyl-0-benzyl-L-seryl-D-isoglutan-iso-aspartate, min with a melting point of 211 to 214 ° C; [a3 + 69.3 °

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a- (4.6 mg / ml, dimethylformamide); D-glucopyranosid-3-0-yl) -D-propionyl -Nlm-benzyl-L-histidyl analysis for C46H52N4O12 (852.91):

D-isoasparagint, 15 calc .: C64.77 H 6.15 N 6.57

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a- found: C 64.66 H 6.46 N 6.54 D-glucopyranosid-3-0-yl) -D-propionyl-y-benzyl-L-glutamyl-D-benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-isoaspartate, D-glucopyranosid-3-0-yl) -acetyl-0-benzyl-L-threonine-D-isoglu-

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-aminate with a melting point of 182 to 188 ° C; [aß5 D-glucopyranosid-3-0-yl) -D -propionyl-L-glutaminyl-D-isoaspa- 20 + 76.3 ° (10 mg / ml, dimethylformamide),

raginate, benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-methionyl-D-isoglutaminate D-glucopyranoside-3 -0-yl) -D-propionyl-ß-benzyl-L ^ asparagyl-D- with a melting point of 234 to 238 ° C; [a5 + 78.0 ° (10 isoasparaginate, mg / ml, dimethylformamide);

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a- 25 Analysis for C41H50N4O11S (806.95): -D-glucopyranosid-3-0-yl) -D-propionyl -L-asparaginyl-D-isomer: C 61.03 H 6.25 N6.94 asparaginate, found: C 60.98 H 6.38 N6.86

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside- 3-0-yl) -D-propionyl-L-prolyl-D-isoasparagi-D-glucopyranosid-3-0-yl) -acetyl-S-benzyl-L-cysteinyl-D-isogluonate and 30 taminate,

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside- 3-0-yl) -D-propionyl-0-benzyl-L-hydroxypro-D-glucopyranosid-3-0-yl) -acetyl-L-phenylalanyl-D-isoglutami-lyl-D-iso-aspartate. nat with a melting point of 229 to 231 ° C; [a5 + 78.6 ° (5th

If you have a stoichiometric equivalent amount of benzyl mg / ml, dimethylformamide); 2-acetamido-4,6-0-benzylidene-2-deoxy-3-0-carboxymethyl-a- 35 Analysis for C45H50N4O11 (822.93):

D-glucopyranoside (Formula 9, R2 = methyl) instead of calc .: C 65.68 H 6.12 N6.81

Benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (D-l-carbofound: C 65.63 H 6.02 N6.62

xyethyl) -aD-glucopyranoside used and this with each of the benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-corresponding compounds obtained in Example 4 D-glucopyranoside-3-0- yl) -acetyl-0-benzyl-L-tyrosyl-D-isogluta-

reacted, the corresponding 40 minutes with a melting point of 241 to 243 ° C. are obtained in the same way; [a3 + 66.7 ° (4.2 protected glycopeptide derivatives: mg / ml, dimethylformamide);

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a- Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

D-glucopyranosid-3-0-yl) -acetylglycyl-D-isoglutaminate with D-glucopyranosid-3-0-yl) -acetyl-L-tryptophanyl-D-isoglutami - a melting point of 258 to 259 ° C .; [a5 + 72.5 ° (3 mg / ml, nat,

Dimethylformamide); 45 benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

Analysis for C38H44N4011 (732.80): D-glucopyranosid-3-0-yl) -acetyl- e-carbobenzyloxy-L-lysyl-D-

calc .: C62.28 H6.05 N7.65 isoglutaminate with a melting point of 215 to 219 ° C;

Found: C 62.31 H 6.18 N7.60 [a] è5 + 66.7 ° (5.5 mg / ml, dimethylformamide);

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a analysis for C50H59N5O13 (938.06): D-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D -isoglutaminate with 50 calc.: C 64.02 H 6.34 N 7.47 a melting point of 223 to 224 ° C; [a5 + 76.9 ° (2.6 found: C 63.79 H 6.51 N7.44

mg / ml, dimethylformamide); Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

Analysis for C39H46N4O11 (746.79): D-glucopyranosid-3-0-yl) -acetyl- ô-carbobenzyloxy-L-ornithyl-

calc .: C 62.72-H 6.21 N7.50 D-isoglutaminate,

found: C 62.57 H 6.51 N7.32 55 benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-gu-nitro-L-arginyl-D-isogluta-D- glucopyranosid-3-0-yl) acetyl-L-valyl-D-isoglutaminate with minate,

a melting point of 237-239 ° C [a5 + 80.9 ° (9 mg / ml, benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-dimethylformamide); D-glucopyranoside -3-0-yl) -acetyl-NIm-benzyl-L-histidyl-D-iso-

Analysis for C41HsoN40ii (774.84): 60 glutaminate,

calc .: C 63.55 H 6.50 N7.33 benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

found: C 63.45 H 6.51 N7.06 D-glucopyranosid-3-0-yl) -acetyl-y-benzyl-L-glutamyl-D-isoglu-

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-aminate, D-glucopyranosid-3-0-yl) -acetyl-L-leucyl-D-isoglutaminate with benzyl- (benzyl -2-acetamido-4,6-0-benzylidene-2-deoxy-a-

a melting point of 209 to 211 ° C; 65 D-glucopyranosid-3-0-yl) -acetyl-L-glutaminyl-D-isoglutaminate,

Analysis for C42H52N4O11 (788.91): benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-

calc .: C63.94 H 6.64 N7.10 D-glucopyranosid-3-0-yl) -acetyl-ß-benzyl-L-asparagyl-D-isoglu-

found: C 63.72 H 6.59 N6.95 taminate,

636 887

18th

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-asparaginyl-D-isoglutamate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-asparaginyl-D-isoglutamate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-prolyl-D-isoglutaminate with a melting point of 224 to 225 ° C ; [a] o4 + 68.1 ° (3.1 mg / ml, dimethylformamide);

Analysis for C41H48N4O11 (772.82):

calc .: C 63.72 H 6.26 N7.25 found: C 63.49 H 6.39 N7.14

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-0-benzyl-L-hydroxyprolyl-D-isoglutaminate with a melting point of 219 up to 221 ° C; Md + 73.2 ° (9 mg / ml, dimethylformamide);

Analysis for C48H54N4O12 (878.89):

calc .: C 65.59 H 6.19 N6.37 found: C 65.49 H 6.42 N6.33

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetylglycyl-D-isoaspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) acetyl-L-alanyl-D-isoasparticate, melting point 222-225 ° C; [a5 + 97.10 (10 mg / ml, dimethylformamide);

Analysis for C38H44N4O11 (732.80):

calc .: C 62.28 H 6.05 N7.65 found: C 62.48 H 6.18 N7.60

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-valyl-D-isoasparticate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-leucyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-isoleucyl-D-iso-aspartate, benzyl- (benzyl-2-acetamido -4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-la-aminobutyryl-D-isoaspa-raginate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-0-benzyl-L-seryl-D-isoasparaginate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-0-benzyl-L-threonyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-methionyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) acetyl-S-benzyl-L-cysteinyl-D-iso-asparaginate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-phenylalanyl-D-isoasparagate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a ~ D-glucopyranosid-3-0-yl) -acetyl-0-benzyl-L-tyrosinyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-tryptophanyl-D-isoasparagate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-e-carbobenzyloxy-L-lysyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-8-carbobenzyloxy-L-ornithyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) acetyl-gu-nitro-L-arginyl-D-isoaspa-raginate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a ~

D-glucopyranosid-3-0-yl) -acetyl-NIm-benzyl-L-histidyl-D-iso-aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-y-benzyl-L-glutamyl-D-iso-5 aspartate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-glutaminyl-D-isoasparagate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a ~ 10 D-glucopyranosid-3-0-yl) -acetyl-ß-benzy 1-L ^ asparagyl-D-iso- asparaginate,

Benzyl- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-asparaginyl-D-isoasparagate,

15 benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-prolyl-D-iso-aspartate and

Benzyl- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucopyranosid-3-0-yl) acetyl-0-benzyl-L-hydroxyprolyl-D-isoaspartate.

20 If a stoichiometrically equivalent amount of the compounds obtained in Examples 6,6 'and 6 "instead of benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-3-0- (Dl-carboxyethyl) - If aD-glucopyranoside is used and these are reacted with each of the corresponding compounds obtained in Example 4, various corresponding compounds of the formula 11 are obtained in the same way; representative examples of this compound are:

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-butyryl-L-alanyl-D-isoglutaminate 30 with a melting point of 232 to 234 ° C; [a5 + 89.6 ° (5 mg / ml, dimethylformamide);

Analysis for C41H50N4O11 (774.88):

calc .: C 63.55 H 6.50 N7.23 found: C 63.75 H 6.62 N7.22 35 benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2- deoxy-aD-glucopyranosid-3-0-yl) -D-butyryl-L-valyl-D-isoglutaminate with a melting point of 273 to 276 ° C; [a] o5 + 94.3 ° (1.4 mg / ml, dimethylformamide);

Analysis for C43H54N4O11 (802.94):

40 calc .: C 64.32 H 6.78 N6.98 found: C 64.00 H 6.72 N6.81

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-butyryl-L-prolyl-D-isoglutaminate, an oil with [ a] è5 + 87.6 ° (5 mg / ml, dimethylformamide); 45 Analysis for C43H52N4O11 (800.92):

calc .: C 64.48 H 6.57 N7.00 found: C 64.20 H 6.52 N7.19

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-hexanoyl-L-alanyl-D-isoglutami-50 nat with one Melting point from 235 to 238 ° C; [a] o + 84.5 ° (5 mg / ml, dimethylformamide);

Analysis for C43H54N4O11 (802.94):

calc .: C 64.32 H 6.78 N6.98 found: C 64.30 H 6.87 N6.98 55 benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2- deoxy-oc-D-glucopyranosid-3-0-yl) -D-hexanoyl-L-valyl-D-isoglutaminate with a melting point of 264 to 266 ° C [a5 + 76.6 ° (3 mg / ml, dimethylformamide) ;

Analysis for C45H58N4O11 (830.99):

60 calc .: C 65.04 H 7.04 N6.74 found: C 65.23 H 7.27 N6.81

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-hexanoyl-L-propyl-D-isoglutamate with a melting point from 80 to 88 ° C; [a] o + 85.7 ° (5 65 mg / ml, dimethylformamide);

Analysis for C45H56N4O11 (828.98):

calc .: C 65.20 H 6.81 N6.76 found: C 65.43 H 6.86 N6.84

19th

636 887

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-decanoyl-L-alanyl-D-isoglutamate with a melting point of 235 to 237 ° C; [a5 + 73.0 ° (5 mg / ml, dimethylformamide),

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-a-5 D-glucopyranosid-3-0-yl) -D-tetradecanoyl-L-alanyl-D-isoglutaminate with a melting point of 228 to 229 ° C; [a5 + 66.4 ° (5 mg / ml, dimethylformamide),

Benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-octadecanoyl-L-alanyl-D-isoglutamate with one Melting point of 225 to 227 ° C; [a5 + 70.7 ° (5 mg / ml, dimethylformamide);

Benzyl- (benzyl-2-benzyloxyacetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-Ò-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 209 to 211 ° C; [a5 + 46.3 ° (5 mg / ml, chloroform);

Analysis for C46H52N4O12 (852.91):

calc .: C64.77 H6.15 N6.57 found: C 64.75 H 6.35 N6.59

Benzyl-2- (benzyl-2-benzyloxyacetamido-4,6-0-benzylidene-20 2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate with a melting point of 200 to 204 ° C; [a5 + 51.8 ° (5 mg / ml, dimethyl sulfoxide);

Analysis for C47H54N4O12 (866.94):

calc .: C65, ll H 6.28 N6.46 25

found: C65.19 H 6.21 N6.30

Benzyl- (benzyl-2-methoxyacetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 188 to 200 ° C; [a5 + 75.9 ° (10 mg / ml, dimethylformamide); 30th

Benzyl-2- (benzyl-2-methoxyacetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate with a melting point of 210 up to 220 ° C; [a5 + 88.1 ° (10 mg / ml, dimethylformamide);

Analysis for C41H50N4O12 (790.88): 35

calc .: C 62.27 H 6.37 N7.08 found: C61.85 H 6.51 N6.91

Benzyl- (benzyl-2-benzamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 217 to 219 ° C ; [a5 + 70.5 ° (5 mg / ml 40 dimethylformamide);

Analysis for C44H48N4O11 (808.90):

calc .: C 65.33 H 5.98 N6.93 found: C 65.10 H 5.90 N6.76

Benzyl- (benzyl-2-benzamido-4,6-0-benzyliden-2-deoxy-a- 45 D-glucopyranosid-3-0-yl) acetyl-L-valyl-D-isoglutaminate with a melting point of 242 to 249 ° C; [a5 + 74.4 ° (5 mg / ml dimethylformamide);

Analysis for C46H52N4O11 (836.95):

calc .: C 66.01 H 6.26 N6.69 50

found: C 65.82 H 6.20 N6.43

Benzyl 2- (benzyl-2-benzamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate with a melting point from 258 to 260 ° C; [a5 + 73.8 ° (5 mg / ml, dimethylformamide); 55

Analysis for C45H50N4O11 • H2O (840.95):

Calc .: C 64.27 H 6.23 N6.66 Found: C 64.64 H 6.38 N6.63

Benzyl-2- (benzyl-2-benzamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutamate with a Melting point from 257 to 259 ° C; [a5 + 73.2 ° (5 mg / ml, dimethylformamide);

Analysis for C47H54N4O11 (850.98):

calc .: C 66.34 H 6.40 N6.58

found: C 66.54 H 6.39 N6.50 65

Benzyl-2- (benzyl-2-benzamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutaminate with a melting point from 148 to 151 ° C; [a5 + 60.8 °

(5 mg / ml, dimethylformamide);

Analysis for C47H52N4O11 (849.97) 8 calc .: C66.49 H 6.17 N6.60 found: C 66.32 H 6.25 N6.58

Benzyl- (benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 211 to 213 ° C ; [a5 + 76.8 ° (5 mg / ml. dimethylformamide);

Analysis for C43H54N4O11 (802.94):

calc .: C64.32 H 6.78 N6.98 found: C 64.05 H 6.84 N6.91

Benzyl- (benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-valyl-D-isoglutaminate with a melting point of 264 to 265 ° C ; [a5 + 74.7 ° (5 mg / ml. dimethylformamide);

Analysis for C45H58N4O11 (830.99):

calc .: C 65.04 H 7.04 N6.74 found: C 64.92 H 6.97 N6.74

Benzyl- (benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-prolyl-D-isoglutaminate with a melting point of 193 to 194 ° C ; [a5 + 58.0 ° (5 mg / ml. dimethylformamide);

Analysis for C45H56N4O11 (828.98):

calc .: C 65.20 H 6.81 N6.77 found: C 65.03 H 6.61 N6.85

Benzyl 2- (benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate with a melting point from 245 to 247 ° C; [a5 + 83.4 ° (5 mg / ml, dimethylformamide);

Analysis for C44H56N4O11 (816.96):

calc .: C 64.69 H 6.91 N6.86 found: C 64.71 H 7.08 N6.78

Benzyl-2- (benzyl-2-caproamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutamate with a melting point from 252 to 253 ° C; [a5 + 86.7 ° (5 mg / ml, dimethylformamide);

Analysis for C40H60N4O11 (845.02):

calc .: C 65.38 H 7.16 N6.63 found: C 65.66 H 6.99 N6.74

Benzyl-2- (benzyl-2-caproamido-4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutaminate with a melting point from 136 to 138 ° C; [a5 + 86.0 °, (5 mg / ml, dimethylformamide);

Benzyl- (benzyl-2-myristamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate, benzyl- (benzyl-2-myristamido -4,6-0-benzyliden-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-valyl-D-isoglutaminate,

Benzyl- (benzyl-2-myristamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -acetyl-L-prolyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-myristamido-4,6-Ó-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate,

Benzyl-2- (benzyl-2-myristamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-iso-glutaminate and

Benzyl-2- (benzyl-2-myristamido-4,6-0-benzyliden-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutaminate.

Example 8

450 ml of 67% acetic acid are heated on a steam bath to 97 ° C. and 5.9 g of benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranoside-3- 0-yl) -D-propionyl-L-valyl-D-isoglutaminate (formula 11, n = 2, X1 = L-valyl, R2 = R6 = methyl). The resulting solution is heated to 97-100 ° C for exactly 7 minutes and then immediately quenched in an ice bath. The resulting solution is evaporated to dryness in vacuo and the residue through

636 887

20th

evaporate twice with water and twice with toluene to remove acetic acid to give the crude product which is mixed with 250 ml ether; the residue is stirred for 15 hours at 22 ° C with a magnetic stirrer. The resulting solid is isolated by filtration and dried to give benzyl-2- (benzyl-2-acetamido-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate (Formula 12A, n = 2, X1 = L-valyl, R2 = R6 = methyl) with a melting point of 221 to 224 ° C; [a5 + 103.5 ° (10 mg / ml, dimethylformamide);

Analysis for C35H48N4O11 (700.80):

calc .: C 59.99 H 6.90 N8.00 found: C 59.56 H 6.92 N7.70

If a stoichiometric equivalent amount of the compounds obtained in Example 7 was substituted for benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate, the corresponding compounds of formula 12A are obtained in the same way; representative examples of this are:

Bunzyl-2- (benzyl-2-acetamido-2-deoxy-aD-glucopyrano-sid-3-0-yl) -D-propional-L-alanyl-D-isoglutaminate with a melting point of 225 to 228 ° C; [ aß5 + 95.8 ° (10 mg / ml, dimethylformamide);

Analysis for C33H44N4O11 (672.74):

calc .: C 58.92 H 6.59 N8.33 found: C 58.51 H 6.51 N8.10

Benzyl-2- (benzyl-2-acetamido-2-deoxy-aD-glucopyrano-sid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutaminate with a melting point of 85 to 98 ° C; [ a] o + 100.8 ° (10 mg / ml, dimethylformamide);

Benzyl- (benzyl-2-acetamido-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 202 to 203 ° C; [aß5 + 65.8 ° ( 2.3 mg / ml, methanol); Analysis for C32H42N4O11 (658.72):

calc .: C 58.35 H 6.43 N8.51 found: C 58.28 H 6.13 N 8.54 and

Benzyl- (benzyl-2-acetamido-2-deoxy-a-D-glucopyranosid-3-0-yl) acetyl-L-valyl-D-isoglutaminate with a melting point of 215 to 222 ° C; [a5 + 79.0 ° (10 mg / ml, dimethylformamide);

Analysis for C34H46N4O11 (686.77):

calc .: C 59.46 H 6.75 N8.16 found: C 59.56 H 6.94 N7.92.

Example 9

A solution of 0.70 g of benzyl 2- (benzyl-2-acetamido-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-iso-glutaminate (formula 12A, n = 2, X1 = L-valyl, R2 = R6 = methyl) and 0.56 g of triphenylmethyl chloride in 10 ml of pyridine is stirred at 22 ° C. for 5 days and then evaporated in vacuo to dryness. The residue is partitioned between 30 ml of chloroform and 30 ml of water. The chloroform phase is extracted two more times with 30 ml of water, dried over magnesium sulfate, concentrated in vacuo and the residue is triturated with 50 ml of ether. The resulting solid is isolated by filtration, washed with ether and dried and gives benzyl-2- (benzyl-2-acetamido-2-deoxy-6-0-triphe-nylmethyl-ad-glucopyranosid-3-0-yl) -D -propionyl-L-valyl-D-isoglutaminate (formula 12B, n = 2, X1 = L-valyl, R2 = R6 = methyl).

If a stoichiometrically equivalent amount of the compounds obtained in example 8 instead of benzyl-2- (ben-zyl-2-acetamido-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L- If valyl-D-isoglutaminate is used, the compounds of the formula 12B are obtained in the same way; is a representative example of these compounds.

Benzyl-2- (benzyl-2-acetamido-2-deoxy-6-0-triphenylme-

thyl-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-iso-glutaminate with a melting point of 108 to 110 ° C; [ate + 65.4 ° (10 mg / ml, chloroform);

Analysis for C52H58N4O11 (915.07):

5 calc .: C68.25 H6.39 N6.12 found: C 68.35 H 6.55 N6.28.

Example 10

A solution of 0.36 g of benzyl 2- (benzyl-2-acetamido-2-10 deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-iso-glutaminate (Formula 12A , n = 2, X1 = L-valyl, R2 = R «= methyl) and 1.0 ml of acetic anhydride in 5 ml of pyridine are kept at 22 ° C. for 16 hours, after which 1 ml of methanol is added and the resulting solution at room temperature 1 is stirred for a further 15 hours. The solution is then evaporated to dryness, the residue partitioned between 20 ml of chloroform and 20 ml of water and the chloroform phase dried over magnesium sulfate and evaporated to dryness to give a crude product which is crystallized from aqueous ethane-20 noi and benzyl -2- (benzyl-2-acetamido-4,6-di-0-acetyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate (formula 12E, n = 2, X1 = L-valyl, R2 = R6 = methyl, R4 = R5 = acetyl) with a melting point of 225 to 241 ° C; [a5 + 93.7 ° (10 mg / ml, dimethylformamide); 25 Analysis for C39H52N4Q13 (784.88):

calc .: C 59.68 H 6.68 N7.14 found: C 60.00 H 6.76 N7.14 results.

If a stoichiometrically equivalent amount of the corresponding acylating agent (either an acid anhydride or an acid chloride) is used instead of acetic anhydride, the corresponding compounds of the formula 12E are obtained in the same way; representative examples of these compounds are: 35 benzyl-2- (benzyl-2-acetamido-4,6-di-0-butyryl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl -D-isoglutami-nat,

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-octanoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate 40 with one Melting point of 207 to 210 ° C; [a5 + 79.3 ° (8 mg / ml, dimethylformamide);

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-stearoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate with a melting point from 200 to 207 ° C; 45 benzyl-2- (benzyl-2-acetamido-4,6-di-0-behenoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutamate with a melting point of 202 to 205 ° C; [a5 + 68.1 ° (5 mg / ml, dimethylformamide) and

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-benzoyl-2-deoxy-a-50 D-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate with a melting point of 169 to 172 ° C.

If a stoichiometrically equivalent amount of the compounds obtained in Example 8 instead of benzyl-2- (ben-zyl-2-acetamido-2-deoxy-aD-glucopyranosid-3-0-yl) -D-pro-55 pionyl-L -valyl-D-isoglutaminate used, the corresponding compounds of formula 12E are obtained in the same way; representative examples of such compounds are:

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-acetyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate 60 with one Melting point from 218 to 219 ° C; [a5 + 86.8 ° (10

mg / ml, methanol);

Analysis for C37H48N4O13 (756.83):

calc .: C 58.72 H 6.39 N7.40 found: C 58.72 H 6.31 N7.19 6.5 benzyl-2- (benzyl-2-acetamido-4,6-di-0-butyryl- 2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamate with a melting point of 187 to 188 ° C; [a5 + 84.0 ° (5 mg / ml, dimethylformamide);

21st

636 887

Analysis for ChHìsNaOu (812.93):

calc .: C 60.58 H 6.94 N6.89 found: C 60.45 H 6.95 N6.76

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-octanoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamate with a melting point of 167 to 168 ° C; [a5 + 76.8 ° (5 mg / ml, dimethylformamide);

Analysis for C49H72N4O13 (925.15):

calc .: C 63.62 H 7.84 N6.06 found: C 63.78 H 7.64 N5.95

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-stearoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamate with a melting point of 175 to 178 ° C; [a5 + 46.8 ° (5 mg / ml, chloroform);

Analysis for C69H112N4O13 (1205.69):

calc .: C 68.74 H 9.36 N4.65 found: C 69.20 H 9.41 N4.50

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-behenoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate with a melting point of 202 to 205 ° C; [a5 + 68.1 '(5 mg / ml, dimethylformamide);

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-acetyl-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutaminate with a melting point from 80 to 85 ° C; [a5 + 82.4 ° (10 mg / ml, dimethylformamide);

Analysis for C39H50N4O13 (782.86):

calc .: C 59.84 H 6.44 N7.16 found: C 59.58 H 6.03 N7.13

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-butyryl-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamate,

Benzyl-2- (benzyl-2-acetamido-4,6-di-0-octanoyl-2-deoxy-a-D-glucopyranosid-3-0-yl) -D-propionyl-L-prolyl-d-isoglutamate,

Benzyl- (benzyl-2-acetamido-4,6-di-0-acetyl-2-deoxy-aD-glucopyranosid-3-0-yl) acetyl-L-alanyl-D-isoglutaminate with a melting point of 185 to 186 ° C; [a5 + 64.8 ° (3 mg / ml, methanol);

Analysis for C36H46N4O13 (742.80):

calc .: C 58.21 H 6.24 N7.54 found: C 58.47 H 6.01 N7.52

Benzyl- (benzyl-2-acetamido-4,6-di-0-butyryl-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 159 to 163 ° C; [a5 + 78.1 ° (6 mg / ml, dimethylformamide);

Benzyl- (benzyl-2-acetamido-4,6-di-0-octanoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-I ^ alanyl-D-isoglutaminate with a melting point of 137 to 140 ° C; [a5 + 68.6 ° (7 mg / ml, dimethylformamide);

Benzyl- (benzyl-2-acetamido-4,6-di-0-stearoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-I ^ alanyl-D-isoglutaminate with a melting point of 140 to 148 ° C; [a5 + 32.8 ° (3 mg / ml, methanol: chloroform, 1: 4);

Benzyl- (benzyl-2-acetamido-4,6-di-0-behenoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 147 to 149 ° C; [a5 + 31.8 ° (3 mg / ml, methanol: chloroform, 1: 4);

Benzyl- (benzyl-2-acetamido-4,6-di-0-benzoyl-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-alanyl-D-isoglutaminate with a melting point of 114 to 117 ° C;

Benzyl- (benzyl-2-acetamido-4,6-di-0-acetyl-2-deoxy-aD-glucopyranosid-3-0-yl) -acetyl-L-valyl-D-isoglutaminate with a melting point of 197 to 205 ° C; [a5 + 79.1 ° (10 mg / ml, dimethylformamide);

Analysis for C38H50N4O13 (770.85):

calc .: C 59.21 H 6.54 N7.27 found: C 59.55 H 6.33 N7.28

Benzyl- (benzyl-2-acetamido-4,6-di-0-butyryl-2-deoxy-a-D-

glucopyranosid-3-0-yl) acetyl-L-valyl-D-isoglutaminate and

Benzyl- (benzyl-2-acetamido-4,6-di-0-octanoyl-2-deoxy-aD-glucopyranosid-3-0-yl) acetyl-L-valyl-D-isoglutaminate with a melting point of 174 to 177 ° C; [a5 + 68.3 ° (8 mg / ml, dimethylformamide).

Example 11

If you repeat the procedure of Example 10, but the benzyl 2- (benzyl-2-acetamido-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate by a stoichiometrically equivalent amount of benzyl 2- (benzyl-2-aceta-mido-2-deoxy-6-0-triphenylmethyl-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate (Formula 12B, n = 2, X1 = L-valyl, R2 = R6 = methyl) is replaced, then benzyl-2- (benzyl-2-acetamido-4-0-acetyl-2-deoxy-6-0- triphenylmethyl-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutamate (formula 12C, n = 2, X1 = L-valyl, R2 = R6 = methyl, R3 = acetyl) .

If a stoichiometrically equivalent amount of the corresponding acylating agent (either an acid anhydride or an acid chloride) is used instead of acetic anhydride, the corresponding compounds of the formula 12C are obtained in the same way.

If a stoichiometrically equivalent amount of the compounds obtained in Example 9 instead of benzyl-2- (benzyl-2-acetamido-2-deoxy-6-0-triphenylmethyl-AD-glucopyra-nosid-3-0-yl) - D-propionyl-L-valyl-D-isoglutaminate used, the corresponding compounds of formula 12C are obtained in the same way; a representative example of this connection is:

Benzyl-2- (benzyl-2-acetamido-4-0-acetyl-2-deoxy-6-0-tri-phenylmethyl-aD-glucopyranosid-3-0-yl) -D-propionyl-L-ala-nyl- D-isoglutaminate with a melting point of 91 to 93 ° C; [a5 + 72.1 ° (10 mg / ml, chloroform);

Analysis for CseHaoNtOn (957.10):

calc .: C 67.77 H 6.32 N5.85 found: C 67.24 H 6.61 N5.67.

Example 12

A mixture of 0.97 g of benzyl-2- (benzyl-2-acetamido-4-0-acetyl-6-0-triphenylmethyl-aD-glucopyranosid-3-0-yl) -D-pro-pionyl-L-valyl -D-isoglutaminate (formula 12C, n = 2, X1 = L-valyl, R2 = R6 = methyl, R3 = acetyl) and 10 ml 70% acetic acid is heated to 100 ° C until a clear solution is obtained (approx . 2 minutes), and then heated for another 2 minutes. The solution is immediately cooled in an ice bath and the precipitate is removed by filtration. The filtrate is evaporated to dryness in vacuo. The residue is triturated with 25 ml of ether and the resulting solid is isolated by filtration, washed with ether and dried in vacuo to give benzyl-2- (benzyl-2-acetamido-4-0-acetyl-aD-glucopyranoside-3-0- yl) -D-propionyl-L-valyl-D-isoglutaminate (formula 12D, n = 2, X1 = L-valyl, R2 = R6 = methyl, R3 = acetyl).

If a stoichiometrically equivalent amount of the compounds obtained in Example 11 instead of benzyl-2- (benzyl-2-acetamido-4-0-acetyl-6-0-triphenylmethyl-aD-glu-copyranosid-3-0-yl) - D-propionyl-L-valyl-D-isoglutaminate used, the corresponding compounds of the formula 12D are obtained in the same way; is an example of such a connection

Benzyl-2- (benzyl-2-acetamido-4-0-acetyl-a-D-glucopyrano-sid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate.

Example 13

If you repeat the procedure of Example 10, but the benzyl 2- (benzyl-2-acetamido-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate by a

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

636 887

stoichiometrically equivalent amount of benzyl-2- (benzyl-2-aceta-mido-4-0-acetyl-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate (formula 12D, n = 2, X1 = L-valyl, R2 = R6 = methyl, R3 = acetyl) and propionic anhydride is used instead of acetic anhydride, benzyl-2- (benzyl-2-acetamido-4-0-acetyl-6-0-propionyl is obtained -aD-glucopy-ranosid-3-0-yl) -D-propionyl-I ^ valyl-D-isoglutaminate (formula 12E, n = 2, X> = L-valyl, R2 = R6 = methyl, R5 = acetyl, R4 = propionyl).

If a stoichiometrically equivalent amount of the corresponding acylating agent (acid anhydride or acid chloride) is used instead of propionic anhydride, the corresponding compounds of the formula 12E are obtained in the same way.

If a stoichiometrically equivalent amount of the compounds obtained in Example 12 instead of benzyl-2- (benzyl-2-acetamido-4-0-acetyl-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl- If D-isoglutaminate is used, the corresponding compounds of the formula 12E are obtained in the same way.

Example 14

A solution of 0.36 g benzyl-2- (benzyl-2-acetamido-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-iso-glutaminate (formula 12A, n = 2, X1 = L-valyl, R2 = R6 = methyl) in 5 ml of pyridine is stirred at 0 ° C., while a solution of 0.095 ml of acetic anhydride in 1 ml of pyridine is added dropwise over the course of 30 minutes. The resulting solution is kept at 0 ° C for 16 hours, then 1 ml of methanol is added and the mixture is evaporated to dryness. The residue thus obtained is distributed between 100 ml of chloroform and 100 ml of water. The chloroform phase is dried over magnesium sulfate and concentrated in vacuo to give 0.36 g of a crude product which is purified by preparative thick layer chromatography and benzyl-2- (ben-zyl-2-acetamido-6-0-acetyl-2-deoxy- aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate (formula 12F, n = 2, X1 = L-valyl, R2 = Re = methyl, Rs = acetyl).

If stoichiometrically equivalent amounts of the corresponding acylating agent (either of the acid anhydride or of the acid chloride) are used instead of acetic anhydride, the corresponding compounds of the formula 12F are obtained in the same way.

If a stoichiometrically equivalent amount of the compounds obtained in Example 8 instead of benzyl-2- (ben-zyI-2-acetamido-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L- If valyl-D-isoglutaminate is used, the compounds of the formula 12F are obtained in the same way; a representative example of such a connection is:

Benzyl-2- (benzyl-2-acetamido-6-0-acetyl-2-deoxy-aD-glu-copyranosid-3-0-yl) -D-propionyl-L-alanyl-D-isoglutaminate with a melting point of 196 up to 198 ° C.

Example 15

A mixture of 0.50 g of benzyl-2- (benzyl-2-acetamido-4,6-0-benzylidene-2-deoxy-aD-glucopyranosid-3-0-yl) -D-propionyl-L-valyl -D-isoglutaminate (formula 11, n = 2, X1 = L-valyl, R2 = R6 = methyl) and 50 mg of a 10% palladium-on-carbon catalyst in 15 ml of 85% acetic acid at 22 ° C. stirred in a hydrogen atmosphere with a magnetic stirrer. The formation of the product (formula 13, n = 2, X = L-valyl, R2 = R6 = methyl) is monitored by thin layer chromatography using a solvent system containing 8: 1: 1 acetonitrile, acetic acid and water. It is generally found that the reaction is complete within 24 to 40 hours, whereupon the catalyst is removed by filtration through a Millipore filter (Teflon) and the filtrate is evaporated to dryness in vacuo, with a return22

is obtained, which is dissolved in 3 ml of methanol. The product is precipitated by adding 8 ml of ethyl acetate. The white solid substance thus obtained is isolated by centrifugation and carefully dried in vacuo to give a white powder which is dissolved in 5 ml of water. This solution is then placed on a column (20 cm x 0.5 cm) with Biorex® 70 (weakly acidic ion exchange resin made from polyacrylic acid). The column is eluted with water and the fractions containing the required product are combined and freeze-dried to give 200 mg of 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L -valyl-D-isoglutamine (formula 13, n = 2, X = L-valyl, R = R1 = hydrogen, R2 = R6 = methyl) with a melting point of 140 to 158 ° C (decomposition); [a4 + 13.6 ° (10 mg / ml, methanol);

is analysis for C2iH36N40n * H20 (538.57):

calc .: C 46.83 H 7.11 N 10.40 found: C 46.63 H 7.23 N 10.26.

If a stoichiometrically equivalent amount of the various products of Example 7 is used instead of benzyl-2-20 (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate, the corresponding glycopeptides of the formula 13 are obtained in the same way. Representative compounds which are obtained in this way are: 25 2- (2-acetamido-2-deoxy- D-glucos-3-0-yl) -D-propionyl-L-leucyl-D-isoglutamine with a melting point of 139 to 142 ° C; [a2 + 52.10 (5.2 mg / ml, methanol);

Analysis for C22H38N4O11 • HzO (552.59):

calc .: C47.82 H7.30 N 10.14 30 found: C 47.90 H 7.21 N9.94

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-isoleucyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-la-aminobutyryl-D-isoglutamine with a melting point of 125 35-132 ° C; [aß5 +47.5 ° (7 mg / ml, methanol);

Analysis for C20H34N4O11 • H2O (551.56):

calc .: C 43.55 H 7.12 N 10.15 found: C 43.22 H 6.14 N9.96

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-40 threonyl-D-isoglutamine with a melting point of 126 to 142 ° C; [aß5 +47.9 ° (10 mg / ml, methanol);

Analysis for C20H34N4O12 • 3H2O (576.57):

calc .: C 41.66 H 6.99 N9.72 found: C 41.92 H 6.41 N9.66 45 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-methionyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-cysteinyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-50 phenylalanyl-D-isoglutamine with a melting point of 140 to 143 ° C; [aß2 +84.4 ° (5.9 mg / ml, methanol);

Analysis for C25H36N40ii «1.5 H2O (595.62):

calc .: C 50.41 H 6.60 N9.4I found: C 50.25 H 6.31 N9.27 55 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-tyrosyl-D-isoglutamine with a melting point of 145 ° C (decomposition); [a5 + 73.7 ° (5.0 mg / ml, methanol),

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-tryptophanyl-D-isoglutamine, 60 2- (2-acetamido-2-deoxy-D-glucos- 3-0-yl) -D-propionyl-L-lysyl-D-iosoglutamine with a melting point of 120 to 130 ° C (decomposition); [aß5 + 47.4 ° (10 mg / ml, methanol); Analysis for C22H39NsOn-1.5 H2O (576.61):

calc .: C45.82 H7.34 N 12.14 65 found : C 45.93 H 7.33 N 12.01

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-ornithyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-

arginyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-histidyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-glutamyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-glutaminyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-asparagyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-asparaginyl-D-isoglutamine,

2- (2-Acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine with a melting point of 143 to 146 ° C; [aß2 + 34.0 ° (12 mg / ml, methanol);

Analysis for C2iH34N40n- h2o (537,551):

calc .: 047.11 H 6.75 N 10.42 found: C 47.09 H 6.40 N 10.67

2- (2-Acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-hydroxyprolyl-D-isoglutamine with a melting point of 135 to 148 ° C; [aß5 + 45.8 ° (3 mg / ml, methanol);

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-leucyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-isoleucyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-a-aminobutylryl-D-isoasparagine,

2- (2-acetamido-2-deoxv-D-glucos-3-0-vl) -D-nroDionvl-L-threonyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-methionyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-cysteinyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-phenylalanyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-tyrosyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-tryptophanyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-lysyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-ornithyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-arginyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-histidyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-glutamyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-glutaminyl-D-isoasparagine,

2- (2-acetramido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L asparagyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-asparaginyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoasparagine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-hydroxyprolyl-D-isoasparagine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-leucyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-isoleucyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-a-aminobutyryl-D-isoglutamine,

23 636 887

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-threonyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-methionyl-D-isoglutamine, 5 2- (2-glycolamido-2-deoxy-D-glucos- 3-0-yl) -D-propionyl-L-cysteinyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-phenylalanyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-10 L-tyrosyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-tryptophanyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-histidyl-D-isoglutamine, 15 2- (2-glycolamido-2-deoxy-D-glucos- 3-0-yl) -D-propiony 1-L-glutamyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-glutaminyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-20 L-asparagyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-asparaginyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, 25 2- (2-glycolamido-2-deoxy-D-glucos- 3-0-yl) -D-propionyl-L-hydroxyprolyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoasparagine,

2- (2-Benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-30 alanyl-D-isoglutamine with a melting point of 150 to 152 ° C; [a] D5 +28 , 5 ° (5 mg / ml, dimethylformamide);

Analysis for C24H34N4O11 • 2H2O (590.60):

calc .: 0 48.81 H 6.49 N9.49 found: 0 48.87 H 5.91 N9.32 35 2- (2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine with a melting point of 154 to 158 ° C; [ct] è5 + 17.4 ° (4 mg / ml, methanol;

Analysis for C26H38N4O11 • 2.5 h2o (627.64):

calc .: 0 49.76 H 6.90 N8.92 40 found: C49.48 H6.56 N8.64

2- (2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L ~ prolyl-D-isoglutamine with a melting point of 167 to 176 ° C; [a5 + 0.5 ° (6 mg / ml, methanol);

Analysis for C26H36N4O11 • 4 h2o (652.67):

45 calc .: 0 47.84 H6.79 N8.58 found: 0 47.69 H 5.86 N8.17

2- (2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-pro-50 pionyl-L-alanyl-D-isoglutamine,

2- (2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-pro-pionyl-L-valyl-D-isoglutamine,

2- (2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-pro-pionyl-L-prolyl-d-isoglutamine, 55 2- (2-trifluoroacetamido-2-deoxy-D- glucos-3-0-yl) -D-pro-pionyl-L-seryl-D-isoglutamine,

2- (2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-pro-pionyl-L-alanyl-D-isoglutamine with a melting point of 112 to 124 ° C;

60 Analysis for C20H34N4O12 • 3H2O (576.57):

calc .: 041.66 H 6.99 N9.72 found: 041.42 H 6.13 N9.71

2- (2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-pro-pionyl-L-valyl-D-isoglutamine, 65 2- (2-methoxyacetamido-2-deoxy-D- glucos-3-0-yl) -D-pro-pionyl-L-prolyl-D-isoglutamine,

2- (2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-pro-pionyl-L-seryl-D-isoglutamine,

636 887

24th

2- (2-Caproamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine with a melting point of 150 to 154 ° C; [aß5 + 50.3 ° (5 mg / ml, dimethylformamide);

Analysis for C23H40N4OU • H2O (566.62):

calc .: C 48.75 H 7.47 N9.89 5

found: C 49.18 H 7.27 N9.95

2- (2-caproamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine with a melting point of 138 to 140 ° C (decomposition); [a5 + 46.5 ° (5 mg / ml, dimethylformamide), 10

2- (2-caproamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-d-isoglutamine,

2- (2-caproamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-i5 alanyl-d-isoglutamine,

2- (2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-d-isoglutamine, 20

2- (2-myristamido-2-deoxy-D0glucos-3-O-yl) -D-propionyl-L-seryl-D-isoglutamine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetylglycyl-D-iso-glutamine with a melting point of 134 ° C (decomposition); [a5 + 24.7 ° (5 mg / ml, methanol); 25th

Analysis for C17H28N4O11.2H2O (500.48):

calc .: C 40.80 H 6.45 NI 1.20 found: C41.31 H 5.99 N 11.11

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 148 ° C (decomposition); 30 [a4 + 18.6 ° (5 mg / ml, methanol);

Analysis for CisFboNtOn • H2O (490.49):

calc .: C 43.55 H 6.50 NI 1.29 found: € 43.10 H 5.90 N 10.94

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-iso-35 glutamine with a melting point of 140 to 150 ° C (decomposition); [a5 + 13.6 ° (10 mg / ml, methanol);

Analysis for C20H34N4O11.1.5 H2O (533.54):

calc .: C 45.02 H 6.99 N 10.50

Found: C45.15 H 6.81 N 10.08 40

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-leucyl-D-isoglutamine with a melting point of 133 to 135 ° C; [a5 + 15.3 ° (7 mg / ml, methanol);

Analysis for CaiH ^ On • 1.5 H2O (547.58):

calc .: C 46.06 H 7.18 N 10.23 45

Found: C 46.28 H 6.84 N9.69

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-isoleucyl-D-isoglutamine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-la-aminobutyryl-D-isoglutamine with a melting point of 133 to 50 143 ° C; [aß5 + 32.7 ° (3 mg / ml, methanol);

Analysis for Ci9H32N40u.2.5 H2O (537.54):

calc .: C 42.45 H 6.93 N 10.42 found: C 42.71 H 6.23 N 10.40

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-iso-55 glutamine with a melting point of 132 ° C (decomposition); [a3 + 19.4 ° (5.6 mg / ml, methanol);

Analysis for CisHboNtiz-H2O (512.49):

calc .: C42.19 H 6.29 N 10.93

Found: C 42.67 H 6.49 N 10.82 60

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-threonyl-D-isoglutamine with a melting point of 124 to 132 ° C (decomposition); [a5 + 15.7 ° (5 mg / ml, methanol);

Analysis for CiiH32N40i2-2.5 H2O (553.54):

calc .: C41.22 H 6.73 N 10.12 63

Found: C 40.73 H 5.80 N 10.00

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-methionyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-cysteinyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylala-nyl-d-isoglutamine with a melting point of 136 to 140 ° C; [a3 + 40.1 ° (5 mg / ml, methanol);

Analysis for C24H34N40ii »H20 (572.58):

calc .: C 50.34 H 6.34 N9.79 found: C 50.54 H 6.38 N9.44

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-tyrosyl-D-isoglutamine with a melting point of 153 ° C (decomposition); [a5 + 37.7 ° (5.0 mg / ml, methanol);

2-acetamido-2-deoxy-d-glucos-3-0-yl-acetyl-L-tryptophanyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-lysyl-D-iso-glutamine with a melting point of 126 to 133 ° C (decomposition); [a5 + 10.0 ° (5 mg / ml, methanol);

Analysis for C21H37N5O11 • 1.5 H2O (562.59):

calc .: C44.83 H 7.16 N 12.44 found: C 44.56 H 6.73 N 12.08

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-ornithyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-arginyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-histidyl-d-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-glutamyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-glutaminyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-asparagyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-asparaginyl-D-isoglutamine;

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine with a melting point of 144 to 146 ° C; [a3 - 10.5 ° (5.9 mg / ml, methanol);

Analysis for C20H32N4O11.1.5 H2O (531.53):

calc .: C45.19 H 6.64 N 10.54 found: C 45.50 H 6.33 N 10.22

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-hydroxy-prolyl-D-isoglutamine with a melting point of 90 to 105 ° C (decomposition); [a5 -5.7 ° (10 mg / ml, methanol);

Analysis for C2oH32N40i2-2.5 H2O (565.55):

calc .: C 42.48 H 6.59 N9.90 found: C 42.68 H 5.59 N9.68

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoasparagine with a melting point of 140 to 145 ° C (decomposition); [a4 + 18.4 ° (10.0 mg / ml, methanol);

Analysis for CnKksNiOi 1 • 2 H2O (500.47):

calc .: C 40.79 H 6.44 NI 1.20 found: C 40.60 H 5.79 N 10.62

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-d-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-leucyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-isoleucyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-a-aminobutyryl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-d-iso-asparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-threonyl-d-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-methionyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-cysteinyl-D-isoasparagine,

2-acetamido-2-deoxy-d-glucos-3-0-yl-acetyl-L-phenylala-nyl-d-isoasparagine,

25th

636 887

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-tyrosyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3T0-yl-acetyl-L-tryptopha-nyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-lysyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-ornithyl-D-isoasparagine,

2-acetamido-2-deoxy-d-glucos-3-0-yl-acetyl-L-arginyl-d-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-histidyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-glutamyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-glutaminyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-asparagyl-d-isoasparagin,

2-acetamido-2-deoxy-d-glucos-3-0-yl-acetyl-L-asparaginyl-D-isoasparagin,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoasparagine,

2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-hydroxypy-rolyl-d-isoasparagine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetylglycyl-d-iso-glutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 115 to 140 ° C; [a] è5 + 10.3 ° (5 mg / ml, methanol);

Analysis for CisH3oN40i2-0.5 H2O (503.46):

calc .: C42.94 H6.21 N 11.13 found: C 43.09 H 6.16 N 10.82

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-leucyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-isoleucyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-cc-amino-butyryl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-d-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-threonyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-methionyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-cysteinyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-acetyl-phenylalanyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-tyrosyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-trypto-phanyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-histidyl-d-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyI-L ~ glutamyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-glutamino-nyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-asparagyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-asparaginyl-d-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-hydroxy-prolyl-D-isoglutamine,

2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoasparagine,

2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 145 to 147 ° C; [a] n + 22.9 ° (5 mg / ml, methanol);

Analysis for C23H32N4O11 • H2O (558.55):

calc .: C 49.46 H 6.14 N 10.03 found: C 48.87 H 6.20 N9.64

2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-iso-glutamine with a melting point of 137 to 149 ° C; [a] o + 13.8 ° (6 mg / ml, methanol);

Analysis for C25H36N40n-2.5 H2O (613.64):

calc .: C 48.93 H 6.73 N9.13 found: C49.09 H 6.30 N9.16

2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-iso-glutamine,

2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylala-nyl-D-isoglutamine,

2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-ala-nyl-D-isoglutamine,

2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-pro-lyl-D-isoglutamine,

2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phe-nylalanyl-D-isoglutamine,

2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 96 to 114 ° C; Md + 15.0 ° (10 mg / ml, methanol);

Analysis for C19H32N4O12.2 H2O (544.53):

calc .: C 41.90 H 6.66 N 10.29 found: C 41.99 H 6.02 N9.74

2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutaminate,

2-caproamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 140 to 145 ° C; [<x] d + 36.2 ° (5 mg / ml, dimethylformamide);

Analysis for C22H38N4O11 (534.58):

calc .: C 49.43 H 7.17 N 10.48 found: C 49.02 H 7.32 N 10.28

2-caproamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine with a melting point of 132 to 134 ° C; [a5 + 29.3 ° (5 mg / ml, dimethylformamide);

Analysis for C24H42N4O11 • H2O (580.65):

calc .: C 49.65 H 7.64 N9.65 found: C 50.06 H 7.65 N9.70

2-caproamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

2-caproamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyr-D-isoglutamine,

2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

636 887

26

2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenyla-lanyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-alanyl-D-isoglutamine with a melting point of 120 to 125 ° C (decomposition); [a5 + 62.1 ° (5 mg / ml, dimethylformamide); Analysis for C20H34N4O11 • H2O (524.54):

calc .: C 45.80 H 6.92 N 10.68 found: C 45.82 H 6.82 N 10.55

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-valyl-D-isoglutamine with a melting point of 156 ° C; [a5 + 48.1 ° (5 mg / ml, methanol);

Analysis for C22H3sN40u-2 H2O (570.61):

calc .: C 46.31 H 7.42 N9.82 found: C 46.06 H 7.05 N9.58

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-pro-lyl-D-isoglutamine with a melting point of 155 ° C; [a5 + 45.2 ° (5 mg / ml, methanol);

Analysis for C2ZH36N4O11> 2 H2O (568.59):

calc .: C 46.47 H 7.09 N9.85 found: C 46.82 H 6.89 N9.81

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-seryl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-alanyl-d-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-valyl-d-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-prolyl-d-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-butyryl-L-seryl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-alanyl-d-isoglutamine with a melting point of 164 ° C (decomposition); [a5 + 57.4 ° (5 mg / ml, dimethylformamide);

Analysis for C22H38N4O11 • 2 H2O (570.61):

calc .: C 46.31 H 7.42 N9.82 found: C45.91 H7.32 N9.57

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-valyl-d-isoglutamine with a melting point of 169 to 170 ° C (decomposition); [a5 + 56.2 ° (5 mg / ml, dimethylformamide);

Analysis for C24H42N4O11 • 0.5 H2O (571.64):

calc .: C 50.43 H 7.58 N9.80 found: C 50.47 H 7.72 N9.66

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-prolyl-D-isoglutamine with a melting point of 168 ° C (decomposition); [a5 + 58.8 ° (5 mg / ml, dimethylformamide); Analysis for C24H40N4011 • 2H2O (596.65):

calc .: C 48.31 H 7.43 N9.39 found: C 48.35 H 7.02 N9.22

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-seryl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-d-glucos-3-0-yl) -D-hexanoyl-L-alanyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-valyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-prolyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-hexanoyl-L-seryl-D-isoglutamine,

2- (2-Acetamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-alanyl-D-isoglutamine with a melting point of 160 to 163 ° C; [aß5 + 55.9 ° (5 mg / ml, dimethylformamide),

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-valyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-prolyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-seryl-L-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-alanyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-valyl-D-isoglutamine, 5 2- (2-glycolamido-2-deoxy-D-glucos- 3-0-yl) -D-decanoyl-L-. prolyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-decanoyl-L-seryl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-tetradecanoyl-10 L-alanyl-D-isoglutamine with a melting point of 162 to 165 ° C (decomposition); [a5 + 39.2 ° (5 mg / ml, dimethylformamide),

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-tetradecanoyl-L-valyl-D-isoglutamine, 15 2- (2-acetamido-2-deoxy-D-glucos- 3-0-yl) -D-tetradecanoyl-L-prolyl-D-isoglutamine,

2- (2-acetamido-3-deoxy-D-glucos-3-0-yl) -D-tetradecanoyl-L-seryl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-tetradeca-20 noyl-L-alanyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-tetradeca-noyl-L-valyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-tetradeca-noyl-L-proiyl-D-isoglutamine, 25 2- (2-glycolamido-2-deoxy-D- glucos-3-0-yl) -D-glucos-3-0-yl) -D-tetradecanoyl-L-seryl-D-isoglutamine,

2- (2-Acetamido-2-deoxy-D-glucos-3-0-yl) -D-octadecanoyl-L-alanyl-D-isoglutamine with a melting point of 145 to 148 ° C, [a5 + 48.1 ° (5 mg / ml, dimethylformamide); 30 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-octadecanoyl-

L-valyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-octadecanoyl-L-prolyl-D-isoglutamine,

2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-octadecanoyl-35 L-seryl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-octadeca-noyl-L-alanyl-D-isoglutamine,

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-octadeca-noyl-L-valyl-D-isoglutamine, 40 2- (2-glycolamido-2-deoxy-D- glucos-3-0-yl) -D-octadeca-noyl-L-prolyl-D-isoglutamine and

2- (2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-octadeca-noyl-I ^ seryl-D-isoglutamine.

If a stoichiometrically equivalent amount of the 45 different products from Example 10 was used instead of benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate, the corresponding compounds of the formula 13 are obtained in the same way. Representative compounds which are obtained in this way are:

2- (4,6-Di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine with a melting point of 165 to 168 ° C (decomposition); [a5 + 47.9 ° (10 mg / ml, methanol);

55 Analysis for C23H36N4O13 (576.57):

calc .: C 47.91 H 6.29 N9.72 found: C 47.55 H 6.50 N9.55

2- (4,6-Di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine with a melting point 60 of 150 to 170 ° C (decomposition); [a5 + 28.3 ° (10 mg / ml, methanol);

Analysis for C25H40N4O13 • 2 H2O (640.63):

calc .: C 46.87 H 6.92 N8.75 found: C 46.93 H 6.22 N8.61 65 2- (4,6-di-0-acetyl-2-acetamido-2-deoxy- D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine with a melting point of 130 to 142 ° C (decomposition); [a5 + 45.3 ° (10 mg / ml, methanol);

2- (4,6-di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-d-isoglutamine,

2- (4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-Di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine with a melting point of 192 ° C (Decomposition); [a5 + 68.3 ° (5 mg / ml, dimethylformamide);

Analysis for C27H44N4O13 (632.68);

calc .: C51.26 H7.01 N8.86 found: C 50.86 H 6.80 N8.37

2- (4,6-di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-0-butyryl-2-methoxyacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-0-butyryl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-Di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine with a melting point of 198 to 200 ° C; [a5 + 45.9 ° (5 mg / ml, methanol); Analysis for C37H64N4O13 (772.95):

calc .: C 57.49 H 8.35 N7.25 found: C 57.52 H 8.27 N7.26

2- (4,6-Di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine with a melting point of 147 to 151 ° C; [a5 + 43.8 ° (3 mg / ml, methanol); Analysis for C37H62N4O ». 1.5 H2O (797.95):

calc .: C 55.69 H 8.21 N7.02 found: C 55.32 H 7.83 N7.08

2- (4,6-Di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine with a melting point of 177 to 179 ° C (decomposition); [a5 + 59.3 ° (5 mg / ml, dimethylformamide);

Analysis for C35H60N4O13 (744.90):

ber .; C 56.44 H 8.12 N7.52 Found: C 56.22 H 7.92 N7.56

27 636 887

2- (4,6-di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-octaonyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 5 2- (4, 6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-d-isoglutamine,

2- (4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-10 yl) -D-propionyl-L-seryl-D-isogIutamine,

2- (4,6-di-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-Di-Ó-octanoyl-2-trifluoroacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 15 2- ( 4,6-di-Ó-octanoyl-2-methoxyacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-octanoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -20 D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-Di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-d-isoglutamine, 25 2- (4, 6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-30 yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-Ó-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-d-isoglutamine,

2- (4,6-Di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, 35 2- (4, 6-di-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-lauroyl-2-methoxyacetamido-2-deoxy-D-glu-40 cos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-0-lauroyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-Di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine with a melting point 45 of 187 ° C,

2- (4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-Di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine with a melting point 50 of 182 to 185 ° C; [a5 + 20.5 ° (3 mg / ml, 20% methanol in chloroform);

2- (4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-55 yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-Di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 60 2- (4, 6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-Ó-stearoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-stearoyl-2-trifluoroacetamido-2-deoxy-D-glucos-65 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-stearoyl-2-methoxyacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-stearoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

636 887

28

2- (4,6-Di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine with a melting point of 175 to 185 ° C;

2- (4,6-di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-Ó-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4,6-di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-d-isoglutamine,

2- (4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-I ^ alanyl-D-isoglutamine,

2- (4,6-di-Ò-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-behenoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-behenoyl-2-trifluoroacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-0-behenoyl-2-methoxyacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-behenoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-Di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine with a melting point of 152 ° C (Decomposition),

2- (4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isogIutamine,

2- (4,6-di-0-benzoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-d-isoglutamine,

2- (4,6-di-Ó-benzoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-Ò-benzoyl-2-methoxyacetamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-benzoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,6-di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -acetylglycyl-D-isoglutaminate,

4,6-Di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 140 to 155 ° C (decomposition ); [a5 + 66.1 ° (10 mg / ml, dimethylformamide);

Analysis for C22H34N4O13 (562.54):

calc .: C 46.97 H 6.09 N9.96 found: C 46.49 H 6.32 N9.68

4,6-Di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine with a melting point of 150 to 161 ° C (decomposition ); [a] o + 22.9 ° (10 mg / ml, methanol); Analysis for C24H38N4O13 • H2O (608.62):

calc .: C 47.36 H 6.62 N9.21 found: C 47.02 H 6.06 N9.07

4,6-di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine, 5 4,6-di-0-acetyl -2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-10 acetyl-L-valyl-D-isoglutamine,

4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine, 15 4,6-di-0-acetyl-2 glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-20 yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-acetyl-2-methoxy-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-acetyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine, 25 4,6-di-0-butyryl-2 acetamido-2-deoxy-D-glucos-3-0-yl-acyl-L-alanyl-D-isoglutamiri with a melting point of 111 to 117 ° C; [a] o5 + 29.7 ° (5 mg / ml, methanol);

Analysis for C26H42N4O13 • 1.5 H2O (645.67);

calc .: C 48.37 H 7.02 N8.67 30 found: C48.17 H6.82 N8.64

4,6-di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine, 35 4,6-di-0-butyryl -2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-4o acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine, 45 4,6-di-0-butyryl-2 glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-0-yl-50 acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-butyryl-2-methoxy-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 55 4,6-di-0-butyryl -2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 139 to 145 ° C; [a] o + 47.5 ° (4mg / ml, dimethylformamide); 60 4,6-di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine with a melting point of 179 to 182 ° C; [a5 + 23.1 ° (10 mg / ml, methanol);

Analysis for C36H62N4O13 • 0.5 CH3OH (774.94):

calc .: C 56.57 H 8.32 N7.23 65 found: C 56.30 H 8.54 N7.29

4,6-di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

29

636 887

4,6-di-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-ìsoglutamine,

4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-octanoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-laianyl-D-isoglutamine,

4,6-di-0-octanoyl-2-methoxy-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-Ò-octanoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-alanyl-D-isoglutamine,

4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-seryl-D-isoglutamine,

4,6-di-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-lauroly-2-methoxy-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-Ò-lauroyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine with a melting point of 150 to 160 ° C,

4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-stearoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-stearoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 5 4,6-di-0-stearoyl-2 methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isogIutamine,

4,6-di-0-stearoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-io acetyl-L-alanyl-D-isoglutamine with a melting point of 148 to 156 ° C; [a] è5 + 13.6 ° (3 mg / ml, 20% methanol in chloroform);

Analysis for CszHiuN ^ u-CHCh (1243.02):

calc .: C 60.88 H 9.33 N4.51 is found: C61.15 H9.03 N4.29

4,6-di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine, 2o 4,6-di-0-behenoyl-2 acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-25 acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine, 3o 4,6-di-0-behenoyl-2 glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4,6-di-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-behenoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-35 acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-behenoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-behenoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 4o 4,6-di-0-behenoyl-2 -myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-45 acetyl-L-valyl-D-isoglutamine,

4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-proplyl-D-isoglutamine,

4,6-di-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine, so 4,6-di-0-benzoyl-2 acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-55 acetyl-L-valyl-D-isoglutamine,

4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4,6-di-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine, 60 4,6-di-0-benzoyl-2 glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-trifluoroacetamido-2-deoxyi-D-glucos-3-65 O-yl-acetyl-L-alanyl-D-isoglutamine,

4,6-di-0-benzoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine and

4,6-di-0-benzoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine.

636 887

If a stoichiometrically equivalent amount of the different products from Example 12 was used instead of benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyra-nosid-3-0-yl) - If D-propionyl-L-valyl-D-isoglutaminate is used, the corresponding compounds of the formula 13 are obtained in the same way. Representative examples of compounds which are obtained in this way are:

2- (4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-acetyl-2-acetam ido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-yalyl-D-isoglutamine,

2- (4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

30th

2- (4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 5 2- (4-0-octanoyl- 2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -i o D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, 15 2- (4-0-lauroyl- 2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-20 propionyl-L-valyl-D-isoglutamine,

2- (4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 25 2- (4-0-lauroyl- 2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-30 yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-lauroyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4,0-lauroyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 35 2- (4-0-stearoyl- 2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4 ~ 0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-40 propionyl-L-alanyl-D-isoglutamine,

2- (4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 45 2- (4-0-stearoyl- 2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-5o propionyl-L-seryl-D-isoglutamine,

2- (4-0-stearoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-

propionyl-L-valyl-D-isoglutamine,

2- (4-0-stearoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 55 2- (4-0-stearoyl- 2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-stearoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -propionyl-L-valyl-D-isoglutamine,

2- (4-0-benzoyl-2-acetamido-2-deoxy-D-gluzcos-3-0-yl) -D-6opropionyl-L-valyl-D-isoglutamine,

2- (4-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-Benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 65 2- (4-0-benzoyl- 2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

31 636 887

2- (4-0-Benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D- 4-0-butyryl-2-myristamido-2-deoxy-D-glucos-3- 0-yl-ace-propionyl-L-prolyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

2- (4-0-Benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D- 4-C> -octanoyl-2-acetamido-2-deoxy-D-glucos-3 -0-yl-acetyl-propionyl-L-alanyl-D-isoglutamine, L-alanyl-D-isoglutamine,

2- (4-0-Benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D- 5 4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3 -0-yl-acetyl-propionyl-L-seryl-D-isoglutamine, L-valyl-D-isoglutamine,

2- (4-0-Benzoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D- 4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3- 0-yl-acetyl-propionyl-L-valyl-D-isoglutamine, L-prolyl-D-isoglutamine,

2- (4-0-Benzoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0- 4-0-C> ctanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl acetyl-yl) -D-propionyl-L-valyl-D-isoglutamine, io L-seryl-D-isoglutamine,

2- (4-0-Benzoyl-2-methoxyacetamido-2-deoxy-D-glucos-3- 4-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-

0-yl) -D-propionyl-L-valyl-D-isoglutamine, L-phenylalanyl-D-isoglutamine,

2- (4-0-Benzoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) - 4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0- yl-ace-

D-propionyl-L-valyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

4-0-Acetyl-2-acetamido-2-deoxy-D-glucos-3-0-acetyl-L-ala- is 4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0 -yl-acenyl-D-isoglutamine, tyl-L-valyl-D-isoglutamine,

4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0- yl-ace-valyl-d-isoglutamine, tyl-L-prolyl-D-isoglutamine,

4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-C) -yl-ace-prolyl-D-isoglutamine, 20 tyl-L-seryl-D-isoglutamine,

4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-Lr 4-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl -ace-

seryl-D-isoglutamine, tyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-0- yl-ace-phenylalanyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

4-0-Acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-25 4-0-Octanoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-L -alanyl-D-isoglutamine, yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-octanoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-L- valyl-D-isoglutamine, yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-octanoyl-2-myristamido-2-deoxy-D-glucos-3-oyl-ace-

L-prolyl-D-isoglutamine, 30 tyl-L-alanyl-D-isoglutamine,

4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-seryl-D-isoglutamine, L-alanyl-D-isoglutamine,

4-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-phenylalanyl-D-isoglutamine, L-valyl-D-isoglutamine,

4-0-Acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-35 4-0-Lauroyl-2-acetamido-2-deoxy-D-glucos-3-0 -yl-acetyl-alanyl-D-isoglutamine, L-prolyl-D-isoglutamine,

4-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl- 4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-

acetyl-L-alanyl-D-isoglutamine, L-seryl-D-isoglutamine,

4-0-acetyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl- 4-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- acetyl-L-alanyl-D-isoglutamine, 40 L-phenylalanyl-D-isoglutamine,

4-0-acetyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-alanyl-D-isoglutamine, L-alanyl-D-isoglutamine,

4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0- yl-acetyl-aianyl-D-isoglutamine, L-valyl-D-isoglutamine,

4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-45 4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0 -yl-acetyl-valyl-D-isoglutamine, L-prolyl-D-isoglutamine,

4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0- yl-acetyl-prolyl-D-isoglutamine, L-seryl-D-isoglutamine,

4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0- yl-acetyl-seryl-D-isoglutamine, 50 L-phenylalanyl-D-isoglutamine,

4-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 4-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-0- yl-acetyl-phenylalanyl-D-isoglutamine, L-alanyl-D-isoglutamine,

4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-4-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl- L-alanyl-D-isoglutamine, acetyl-L-alanyl-D-isoglutamine,

4-0-Butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-55 4-0-Lauroyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-L -valyl-D-isoglutamine, yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-lauroyl-2-myristamido-2-deoxy-D-glucos-3-0-yl- ace-L-prolyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-seryl-D-isoglutamine, 60 L-alanyl-D-isoglutamine,

4-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-phenylalanyl-D-isoglutamine, L-valyl-D-isoglutamine,

4-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl- 4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-alanyl-D-isoglutamine, L-prolyl-D-isoglutamine,

4-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl- 65 4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl acetyl-lalanyl-D-isoglutamine, L-seryl-D-isoglutamine,

4-0-butyrayl-2-methoxyacetamido-2-deoxy-D-glucos-3-0- 4-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-

yl-acetyl-L ^ alanyl-D-isoglutamine, L-phenylalanyl-D-isoglutamine,

636 887

32

4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-alanyl-D-isoglutamine,

4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-valyl-D-isoglutamine,

4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-prolyl-D-isoglutamine,

4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-seryl-D-isoglutamine,

4-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-phenylalanyl-D-isoglutamine,

4-0-stearoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-StearoyI-2-trifIuoracetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-stearoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-Ó-stearoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-valyl-D-isoglutamine,

4-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-prolyl-D-isoglutamine,

4-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-seryl-D-isoglutamine,

4-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-tyl-L-phenylalanyl-D-isogiutamine,

4-0-benzoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine and

4-0-Benzoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine.

If a stoichiometrically equivalent amount of the various products from Example 13 was used instead of benzyl-2- (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyra-nosid-3-0-yl) - If D-propionyl-L-valyl-D-isoglutaminate is used, the corresponding compounds of the formula 13 are obtained in the same way. Representative compounds which are obtained in this way are:

2- (4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 5 2- ( 4-0-acetyl-6-0-butyryl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-butyryl-2-myristamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-i o 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6 ~ 0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 15 2- ( 4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glu-20 cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-I ^ alanyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, 25 2 - (4-0-acetyl-6-0-octanoyl-2-benzamido-2-deoxy-D-glu-cos-3-Ò-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-methoxyacetamido-2-deoxy-30 D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-octanoyl-2-myristamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-I ^ valyl-D-isoglutamine, 35 2- ( 4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-40 0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, 45 2- ( 4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-benzamido-2-deoxy-D-glucos-50 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-gluc'os-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-lauroyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 55 2- ( 4-0-acetyl-6-0-lauroyl-2-myristamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-60 3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-I ^ alanyl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, 65 2- ( 4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

33 636 887

2- (4-0-Acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glu- 2- (4-0-Octanoyl-6-0-acetyl-2-glycolamido-2-deoxy- D-glu-

cos-3-0-yl) -D-propionyl-L-alanyl-d-isoglutamine, cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glu 2- (4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy- d-glu-

cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-stearoyl-2-benzamido-2-deoxy-D-glucos-5 2- (4-0-Octanoyl-6-0-acetyl-2-glycolamido-2-deoxy -D-glu-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-stearoyl-2-trifluoroacetamido-2-deoxy-D- 2- (4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy-D- glu-glucos-3-0-yl) -D-propionyl-Lxvalyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-acetyl-6-0-stearoyl-2-methoxyacetamido-2-deoxy- 2- (4-0-octanoyl-6-0-acetyl-2-benzamido-2-deoxy-D-glu-

D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 10 cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-stearoyl-2-myristamido-2-deoxy-D-glu 2- (4-0-Octanoyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy- D-

cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos- 2- (4-0-octanoyl-6-0-acetyl-2-methoxyacetamido-2-deoxy- 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-15 2- (4-0-Octanoyl-6-0-acetyl-2-myristamido-2-deoxy -D-glu-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos- 2- (4-0-Lauroyl-6-0-acetyl-2-acetamido-2-deoxy- D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos- 2- (4-0-Lauroyl-6-0-acetyl-2-acetamido-2-deoxy- D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, 20 3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glu 2- (4-0-Lauroyl-6-0-acetyl-2-acetamido-2-deoxy- D-glucos-

cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glu 2- (4-0-Lauroyl-6-0-acetyl-2-acetamido-2-deoxy- D-glucos-

cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glu-25 2- (4-0-Lauryl-6-0-acetyl-2-glycolamido-2-deoxy -D-glucos-cos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glu 2- (4-0-Lauroyl-6-0-acetyl-2-glycolamido-2-deoxy- D-glu-

cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-benzamido-2-deoxy-D-glucos- 2- (4-0-Lauroyl-6-0-acetyl-2-glycolamido-2-deoxy- D-glu-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 30 cos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-trifluoroacetamido-2-deoxy-D- 2- (4-0-Lauroyl-6-0-acetyl-2-glycolamido-2-deoxy-D- glu-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-methoxyacetamido-2-deoxy- 2- (4-0-Lauroyl-6-0-acetyl-2-benzamido-2-deoxy-D-glucos- D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Acetyl-6-0-benzoyl-2-myristamido-2-deoxy-D-glu-35 2- (4-0-Lauroyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy -D-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 2- (4-0-lauroyl-6-0-acetyl-2-methoxyacetamido-2- deoxy-0-yl) -D-propionyl-L-valyl-D-isoglutamine, D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 2- (4-0-lauroyl-6-0-acetyl-2-myristamido-2- deoxy-D-glu-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, 40 cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 2- (4-0-stearoyl-6-0-acetyl-2-acetamido-2- deoxy-D-glucos-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 2- (4-0-stearoyl-6-0-acetyl-2-acetamido-2- deoxy-D-glucos-0-yl) -D-propionyl-L-seryl-D-isoglutamine, 3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-Butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-45 2- (4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy -D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 3-0-yl) -D-propionyl-I ^ alanyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 2- (4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy- D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 2- (4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy- D-glu-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 50 cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 2- (4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy- D-glu-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-benzamido-2-deoxy-D-glucos- 2- (4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy- D-glu-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-Butyryl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-D- 55 2- (4-0-Stearoyl-6-0-acetyl-2-glycolamido-2-deoxy-D -glu-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-methoxyacetamido-2-deoxy-D- 2- (4-0-stearoyl-6-0-acetyl-2-benzamido-2-deoxy-D- glucos-glucos-3-0-yl) -D-propionyl-I ^ valyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-butyryl-6-0-acetyl-2-myristamido-2-deoxy-D-glu 2- (4-0-stearoyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy- D-

cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 60 glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 2- (4-0-stearoyl-6-0-acetyl-2-methoxyacetamido-2-deoxy- 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 2- (4-0-stearoyl-6-0-acetyl-2-myristamido-2-deoxy- D-glu-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine, cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-Octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-65 2- (4-0-Benzoyl-6-0-acetyl-2-acetamido-2-deoxy -D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 2- (4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy- D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine, 3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

636 887

34

2- (4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-O-ylj-D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-benzoyl-6-Ó-acetyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (4-0-benzoyl-6-Ó-acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yI) -D-propionyl-L-valyl-D-isoglutamine,

2- (4-0-benzoyl-6-0-acetyl-2-myristamido-2-deoxy-D-glu-cos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-Ó-butyryl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glu-cos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-butyryl-2-myristamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyI-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 5 4-0-acetyl-6-0 octanoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-octanoyl-2-myristamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-i o yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-prolyl-D-isoglutamine, 15 4-0-acetyl-6-0 -lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-20 O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine, 25 4-0-acetyl-6-0 -lauroyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-30 O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-glu-cos-3-O-yl-acetyl-I ^ alanyl-D-isoglutamine,

4-0-acetyl-6-0-lauroyl-2-methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 35 4-0-acetyl-6-0 lauroyl-2-myristamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-40 O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine, 45 4-0-acetyl-6-0 stearoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-l ^ phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-5o O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine, 55 4-0-acetyl-6-0 stearoyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-benzamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-trifluoroacetamido-2-deoxy-D-eo glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-stearoyl-2-myristamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 65 4-0-acetyl-6-0 benzoyl-2-acetamido-2-deoxy-d-glucos-3-0-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

35 636 887

4-0-acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3- 4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-

O-yl-acetyl-L-prolyl-D-isoglutamine, 3-0-yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3- 4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-

O-yl-acetyl-L-seryl-D-isoglutamine, 3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3- 5 4-0-octanoyl-6-Ó-acetyl-2-benzamido-2-deoxy-D-glucos -3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine, O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-octanoyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-DO-yl- acetyl-L-alanyl-D-isoglutamine, glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-octanoyl-6-0-acetyl-2-methoxyacetamido-2-deoxy-DO-yl- acetyl-L-valyl-D-isoglutamine, io glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-octanoyl-6-0-acetyl-2-myristamido-2-deoxy-D-glucos- O-yl-acetyl-L-prolyl-D-isoglutamine, 3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-lauroyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 3-0-O-yl-acetyl-L-seryl-D-isoglutamine, yl-acetyl-L-alanyl-D-isoglutamine,

4-0-Acetyl-6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-15 4-0-Lauroyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos -3-0-O-yl-acetyl-L-phenylalanyl-D-isoglutamine, yl-acetyl-L-valyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-benzamido-2-deoxy-D-glucos-3- 4-0-lauroyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 3-0-O-yl-acetyl-L-alanyl-D-isoglutamine, yl-acetyl-L-prolyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-trifluoroacetamido-2-deoxy-D- 4-0-lauroyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-

glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 20 yl-acetyl-L-seryl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-methoxyacetamido-2-deoxy-D- 4-0-lauroyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-

glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-acetyl-6-0-benzoyl-2-myristamido-2-deoxy-D-glucos- 4-0-lauroyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-

3-O-yl-acetyl-L-alanyl-D-isoglutamine, O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0- 25 4-0-lauroyl-6-0-acetyl-2-glycolamido-2-deoxy-D -glucos-3-yl-acetyl-L-alanyl-D-isoglutamine, O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0- 4-0-lauroyl-6-0-acetyl-2-glycolamido-2-deoxy-D- glucos-3-yl-acetyl-L-valyl-D-isoglutamine, O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0- 4-0-lauroyl-6-0-acetyl-2-glycolamido-2-deoxy-D- glucos-3-yl-L-prolyl-D-isoglutamine, 30 O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0- 4-0-lauroyl-6-0-acetyl-2-glycolamido-2-deoxy-D- glucos-3-yl-acetyl-L-seryl-D-isoglutamine, O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0- 4-0-lauroyl-6-0-acetyl-2-benzamido-2-deoxy-D- glucos-3-yl-acetyl-L-phenylalanyl-D-isoglutamine, O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3- 35 4-0-lauroyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glu -O-yl-acetyl-L-alanyl-D-isoglutamine, cos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-lauroyl-6-0-acetyl-2-methoxyacetamido-2-deoxy-DO-yl- acetyl-L-valyl-D-isoglutamine, glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-lauroyl-6-0-acetyl-2-myristamido-2-deoxy-d-glucos- 3-O-yl-acetyl-L-prolyl-D-isoglutamine, 40 O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 3-O-yl-acetyl-L-seryl-D-isoglutamine, O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos- 3-O-yl-acetyl-L-phenylalanyl-D-isoglutamine, O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-0- 4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy-D- glucos-3-yl-acetyl-L-alanyl-D-isoglutamine, O-yl-acetyl-I ^ prolyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glu 4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- cos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-methoxyacetamido-2-deoxy-D- 4-0-stearoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-

glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine, 50 O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-butyryl-6-0-acetyl-2-myristamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 3-O-yl-acetyl-L-alanyl-D-isoglutamine, O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 3-O-yl-acetyl-L-alanyl-D-isoglutamine, O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 55 4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos -3-O-yl-acetyl-l-valyl-D-isoglutamine, O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 3-O-yl-acetyl-L-prolyl-D-isoglutamine, O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 3-

O-yl-acetyl-L-seryl-D-isoglutamine, 6o O-yl-acetyl-L-phenylalanyl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 4-0-stearoyl-6-0-acetyl-2-benzamido-2-deoxy-D-glucos- 3-O-yl-acetyl-I ^ phenylalanyl-D-isoglutamine, O-yl-acetyl-I ^ alanyl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucose-4-0-stearoyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-D-3-O- yl-acetyl-L ^ alanyl-D-isoglutamine, glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-65 4-0-stearoyl-6-0-acetyl-2-methoxyacetamido-2-deoxy-D-3-O -yl-acetyl-L-valyl-D-isoglutamine, glucos-3-O-yl-acetyl-L-alanyl-D-ìsoglutamìn,

4-0-octanoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos- 4-0-stearoyl-6-0-acetyl-2-myristamido-2-deoxy-D-glucos-3- O-yl-acetyl-L-prolyl-D-isoglutamine, 3-O-yl-acetyl-L-alanyl-D-isoglutamine,

636 887

36

4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetly-L-alanyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3- 5 O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylalanyl-D-ìsoglutamine, ok

4-0-benzoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine,

4-0-benzoyl-6-0-acety] -2-glycolamido-2-deoxy-D-glucos-3-15 O-yl-acetyl-L-prolyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-seryl-D-isoglutamine,

4-0-benzoyl-6-0-acetyI-2-glycolamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-phenylaalanyl-D-isoglutamine, 20

4-0-benzoyl-6-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-trifluoroacetamido-2-deoxy-D-glu - cos-3-O-yl-acetyl-L-alanyl-D-isoglutamine,

4-0-benzoyl-6-0-acetyl-2-methoxyacetamido-2-deoxy-D-25 glucos-3-O-yl-acetyl-I ^ alanyl-D-isoglutamine, and

4-0-Benzoyl-6-0-acetyl-2-myristamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine.

If a stoichiometrically equivalent amount of the various products of Example 14 was used instead of benzyl-2- 30 (benzyl-2-acetamido-4,6-0-benzyliden-2-deoxy-aD-glucopyra-nosid-3-0-yl) -D-propionyl-L-valyl-D-isoglutaminate, the corresponding compounds of the formula 13 are obtained in the same way. Representative compounds which are obtained in this way are: 35

2- (6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D- 40 propionyl-L-alanyl-D-isoglutamine,

2- (6-0-acetyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (6-0-Acetyl-2-Glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 45

2- (6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-AcetyI-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (6-0-acetyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D- 50 propionyl-L-seryl-D-isoglutamine,

2- (6-0-acetyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-Acetyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine, 55

2- (6-0-acetyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-acetyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D- 60 propionyl-L-valyl-D-isoglutamine,

2- (6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine, 6.5

2- (6-0-butyryl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (6-0-butyry] -2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (6-0-butyryl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (6-0-butyryl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-butyryl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-butyryl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-butyryl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (6-0-octanoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (6-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-octanoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-octanoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-octanoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-seryl-D-isoglutamine,

2- (6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

2- (6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-I ^ seryl-D-isoglutamine,

2- (6-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-lauroyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-lauroyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-lauroyl-2-myristamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-valyl-D-isoglutamine,

2- (6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-prolyl-D-isoglutamine,

2- (6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine,

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636 887 38

6-0-octanoyr-2-glycòlamidd-2-deoxy-D-glucos-3-0-yl-ace- 6-0-stearoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl- ace-tyl-L-prolyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace- 6-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-tyl-L-seryl-D-isoglutamine, L-alanyl-D-isoglutamine,

6-0-octanoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-5 6-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl acetyl-tyl-L-phenylalanyl-D-isoglutamine, L-valyl-D-isoglutamine,

6-0-octanoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-ace- 6-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3 ~ 0-yl- acetyl

tyl-L-alanyl-D-isoglutamine, L-prolyl-D-isoglutamine,

6-0-octanoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0- 6-Ó-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-

yl-acetyl-L-alanyl-D-isoglutamine, io L-seryl-D-isoglutamine,

6-0-octanoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0- 6-0-behenoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-yl- acetyl-L-alanyl-D-isoglutamine, L-phenylalanyl-D-isoglutamine,

6-0-octanoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-ace- 6-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-tyl-L-alanyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl is 6-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl -ace-L-alanyl-D-isoglutamine, tyl-L-valyl-D-isoglutamine,

6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-

L-valyl-D-isoglutamine, tyl-L-prolyl-D-isoglutamine,

6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-

L-prolyl-D-isoglutamine, 20 tyl-L-seryl-D-isoglutamine,

6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-behenoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-

L-seryl-D-isoglutamine, tyl-L-phenylalanyl-D-isoglutamine,

6-0-lauroyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-behenoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl- ace-

L-phenylalanyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl-25 6-0-behenoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-L -alanyl-D-isoglutamine, yl-acetyl-l-alanyl-D-isoglutamine,

6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-behenoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-L- valyl-D-isoglutamine, yl-acetyl-I ^ alanyl-D-isoglutamine,

6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-behenoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl- ace-L-prolyl-D-isoglutamine, 30 tyl-L-alanyl-D-isoglutamine,

6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-benzoyl-2-acetamido-2-deoxy-d-glucos-3-0-yl- acetyl-LL-seryl-D-isoglutamine, alanyl-D-isoglutamine,

6-0-lauroyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl- acetyl-L-phenylalanyl-D-isoglutamine, L-valyl-D-isoglutamine,

6-0-lauroyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl-35 6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl acetyl-L-alanyl-D-isoglutamine, L-prolyl-D-isoglutamine,

6-0-lauroyl-2-trifluoroacetamido-2-deoxy-d-glucos-3-0-yl- 6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-

acetyl-L-alanyl-D-isoglutamine, L-seryl-D-isoglutamine,

6-0-lauroyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-yl- 6-0-benzoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- acetyl-L-alanyl-D-isoglutamine, 40 L-phenylalanyl-D-isoglutamine,

6-0-lauroyl-2-myristamido-2-deoxy-D-glucos-3-0-yl-ace- 6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-

tyl-L-alanyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine,

6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 6-0-benzoyl-2-glycolamido-2-deoxy-glucos-3-0-yl- acetyl-L-alanyl-D-isoglutamine, valyl-D-isoglutamine,

6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-45 6-0-benzoyl-2-glycolamido-2-deoxy-d-glucos-3-0-yl acetyl-L-valyl-D-isoglutamine, L-prolyl-D-isoglutamine,

6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-

L-prolyl-D-isoglutamine, tyl-L-seryl-D-isoglutamine,

6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl- 6-0-benzoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl- ace-

L-seryl-D-isoglutamine, 50 tyl-L-phenylalanyl-D-isoglutamine,

6-0-stearoyl-2-acetamido-2-deoxy-D-glucos-3-0-yl-acetyl-L- 6-0-benzoyl-2-benzamido-2-deoxy-D-glucos-3-0- yl-acetyl-phenylalanyl-D-isoglutamine, L-alanyl-D-isoglutamine,

6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-6-0-benzoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl-

tyl-L-alanyl-D-isoglutamine, acetyl-L-alanyl-D-isoglutamine,

6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace-55 6-0-benzoyl-2-methoxyacetamido-2-deoxy-D-glucos-3-0-tyl -L-valyl-D-isoglutamine, yl-acetyl-L-alanyl-D-isoglutamine and

6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace- 6-0-benzoyl-2-myristamido-2-deoxy-D-glucos-3-0-yl- ace-

tyl-I ^ prolyl-D-isoglutamine, tyl-L-alanyl-D-isoglutamine.

6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace- using methods well known to those skilled in the art of tyl-L-seryl-D-isoglutamine, 60 carbohydrate chemistry, in particular

6-0-stearoyl-2-glycolamido-2-deoxy-D-glucos-3-0-yl-ace- by crystallization, the compounds of formula 13 can be tyl-L-phenylalanyl-D-isoglutamine, and / or the formula I into the individual a and ß anomers

6-0-stearoyl-2-benzamido-2-deoxy-D-glucos-3-0-yl-acetyl- are separated.

L-alanyl-D-isoglutamine,

6-0-stearoyl-2-trifluoroacetamido-2-deoxy-D-glucos-3-0-yl- 65 Example 16 acetyl-L-alanyl-D-isoglutamine, the antigen mixture used consists of 20 jag Arsanil-

6-0-stearoyl-2-methoxyacetamido-2-deoxy-d-glucos-3-0-yl acid / tyrosine and 100 jag protein [either bovine serum al-acetyl-L-alanyl-D-isoglutamine, bumin (BSA ) or ovalbumin]. The antigen mixture and the

39

636 887

Compounds to be tested are dissolved in saline per guinea pig in the doses given in the table below and emulsified with an equal volume of incomplete Freund's adjuvant (FIA). Groups of 10 guinea pigs are used for each test compound 5 unless otherwise indicated, and each guinea pig is injected subcutaneously into the neck region with 0.1 ml of the above emulsion. In all tests, a comparison group received the above antigen mixture, emulsified with Freund's incomplete adjuvant, and in the overwhelming majority io of the tests, the test compound was also treated with 2- (2-acetamido-2-deoxy-D-glucos-3) under the same conditions -0-yl) -D-propionyl-L-alanyl-D-isoglutamine compared.

After 14 days, all animals are subjected to the dew test using 25 μg arsamil acid / tyrosine in combination with either bovine serum albumin or ovalbumin (bovine serum albumin is used in this test if ovalbumin is present in the antigen mixture and vice versa) and this was administered intradermally into the flanks of the animals in 0.1 ml saline. The efficacy of the test compounds to stimulate the delayed hypersensitivity reaction to arsanilic acid / tyrosine is then calculated by multiplying the average area of the skin reaction after 24 hours by a number from 1 to 3, which is a measure of the degree of observed with each skin reaction 25 is infiltration. The procedure is therefore as follows: skin tests with a high degree of infiltration are rated as +, and the number 3 is assigned to them, skin tests with a lower level of infiltration than +

rated, and they are assigned the number 2, while 30 skin reactions without infiltration are rated 0, and they are assigned the number 1. From these numbers, the sum of the animals in a group is then formed, whereupon the average number obtained is multiplied by the average area of the observed skin reaction. 35 Thus, the efficacies include the degree of infiltration in combination with the average area observed in the skin test. The average efficacies of the test compounds are given in Table 1 in column 1, based on Freund's incomplete adjuvant, 40 which has the value 1.

On day 42, all animals are bled out by cardiac puncture and the sera are tested by passive hemagglutination or by radioimmunological test using the method of Farr (P. Minden and RS Farr in "Handbook of 45 Experimental Immunology", published by DM Weir, chapter 15 , Volume 1, Blackwell Scientific Publications, Oxford) using bovine serum albumin labeled with I25 iodine on bovine serum albumin antibody or ovalbumin antibody. The average efficacies of these 50 tests are given in column 3 of Table I below, based on Freund's incomplete adjuvant, which was 1.

On day 42, all surviving animals are subjected to the skin test using 10 (ig protein (either bovine serum albumin, if present in the antigen mixture, 55 or ovalbumin). The efficacy of the test compounds after 24 hours to stimulate the delayed hypersensitivity reaction to that Protein, based on incomplete Freund's adjuvant, which has the value 1, are then determined in exactly the same way as described above for the delayed hypersensitivity reaction to arsanilic acid / tyrosine and are shown in column 2 of Table I below.

65

Table I

Test connection

Dose ed

Average effectiveness

Column 1 Delayed hypersensitivity to arsanilic acid / tyrosine

Column 2 Delayed hypersensitivity to protein antigen

Column 3

Antibody

pertiter against

Protein-

antigen

FIA - 1st

2- (2-Acetamido-2- 50a 5.7

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

alanyl-D-isoglutamine

2- (2-Acetamido-2- 52a 12.0b deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

valyl-D-isoglutamine

2 - (- Acetamido-2- 51a 7.2

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-a-

aminobutyryl-D-iso-

glutamine

2- (2-Acetamido-2- 52a 9.1

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

threonyl-D-isogluta-

min

2- (2-Acetamido-2- 20 6.2 °

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

tyrosyl-D-isoglutamine

2- (2-acetamido-2- 50 11.5

deoxy-D-glucos-3-O- »

yl) -D-propionyl-L-

prolyl-D-isoglutamine

2- (2-Benzamido-2- 55a 4.3

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

alanyl-D-isoglutamine

2-acetamido-2- 50 10.0

deoxy-D-glucos-3-O-

yl-acetyl-L-alanyl-D-

isoglutamine

2-Acetamido-2- 51a 4.7 deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine

2-acetamido-2- 49a 10.4

deoxy-D-glucos-3-O-

yl-acetyl-L-a-amino-

butyryl-D-isogluta-

min

2-Acetamido-2-50 9.3d deoxy-D-glucos-3-O-yl-acetyl-l-seryl-D-iso-glutamine

2-acetamido-2- 51a 5.0 deoxy-D-glucos-3-O-yl-acetyl-L-threonyl-D-isoglutamine

2-Acetamido-2- 50a 10.1 deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine

12.0

37.2b

21.8

30.4

12.2C

12.0

22.3

10.2

15.0

38.3

4.2d

21.5

8.6

8.1

56.7b

10.5

9.2

15.6C

15.7

12.3

13.4

8.1

22.6

19.3d

7.9

17.4

636 887

40

Test connection

Dose Average Efficacy "Ed

Column 1 Delayed hypersensitivity to arsanilic acid / tyrosine

Column 2 Delayed hypersensitivity to protein antigen

Column 3

Antibody

pertiter against

Protein-

antigen

4.1

21.0

9.6

Group number

20th

Number of dogs

2-acetamido-2-deoxy-D-glucos-3-O-yl-D-lactyl-L-alanyl-D-isoglutamine

2-acetamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine

1

4th

1500 | ig

Nothing

14.5

14.4

16.6

2nd

4th

600 jig

Nothing

25 3

4th

240 jig

Nothing

4th

4th

96 ^ g

Nothing

5

4th

38.4 m

Nothing

12.0

10.8

5.2

6

4th

Nothing

1500 jig

7

4th

Nothing

600 jig

30 8

4th

Nothing

240 jig

9

4th

Nothing

96 jig

10th

4th

Nothing

38.4 jig

17.0

16.6

11.9

11

8th

Nothing

Nothing

2-glycolamido-2- 49a 16.4 20.3 12.9

deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine

2-Benzamido-2- 54a 8.1 13.8 11.6

deoxy-D-glucos-3-O-yl-acetyl-L-alanyl-D-isoglutamine

2- (2-acetamido-2- 51a deoxy-D-glucos-3-O-yl) -D-butyryl-L-ala-nyl-D-isoglutamine 2- (2-acetamido-3- 53a deoxy-D- glucos-3-O-yl) -D-hexanoyl-L-ala-nyl-D-isoglutamine 2- (4,6-di-0-acetyl-2- 58a acetamido-2-deoxy-D-glucos-3- 0-yl) -D-propionyl-L-alanyl-D-isoglutamine 2- (4,6-di-0-acetyl-2- 60a acetamido-2-deoxy-D-glucos-3-0-yl) -D -propionyl-L-valyl-D-isoglutamine

2- (4,6-Di-0-octanoyl-74a 7.6 15.1 18.2

2-acetamido-2-deoxy-D-glucos-3-O-yl) -D-propionyl-L-alanyl-D-isoglutamine

4,6-di-0-acetyl-2-ace-59a 14.1 13.1 7.2

tamido-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isogluta-min

Footnotes to Table I a dose 0.1 jiMol b 5 animals in the test group

0 Efficacy, based on the efficacy of a 20-jig dose of 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine d efficacy on Freund's Incomplete Adjuvant e The actual response to Freund's Incomplete Adjuvant, whether it is a skin test or the synthesis of antibodies in body fluids, is extremely variable, in contrast to the response either with Freund's Complete Adjuvant or the test compounds administered in incomplete Freund's adjuvant. This leads to a high degree of randomness of the efficacies, which are calculated by forming the quotient from the average titer of the test compound and the average titer of the comparison group with incomplete Freuns adjuvant in the same test. Therefore, the efficacies of the test compounds were calculated as follows: The average effectiveness of

2- (2-Acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D-isoglutamine from a large number of tests is determined and the effectiveness of the test compound is incomplete Freund's adjuvant, which has a value of 1, based on the effectiveness of the test compound, based on the effectiveness of 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl -L-alanyl-d-isoglutamine in the same test, with the average effectiveness of 2- (2-acetamido-2-deoxy-D-glucos-3-0-yl) -D-propionyl-L-alanyl-D- isoglutamine multipli-10 adorned.

Example 17

A. 48 dogs were divided into groups and vaccinated with the amounts of test compound (per kg body weight) given in the following table:

Table II

The results are as follows:

(a) All dogs in groups 1 and 2 and two of the dogs in group 3 showed severe depression, excessive salivation and vomiting.

40 (b) None of the dogs in groups 6 to 11 showed the severe symptoms described in (a) above. However, all dogs in group 6, a dog in group 7 and a dog in group 11 (the control group) showed twitching of the eye muscles, which may have been an abnormal symptom 45, since all dogs with this symptom came from the same litter (and during of the test were kept together in the same cage).

B. Seven cats were divided into groups and vaccinated with the amounts of Test-50 compounds (per kg body weight) shown in the table below.

Table III

55

60

65

Group number

Number of cats

2- (2-acetamido-2- 2-acetamido-2-de-deoxy-oxy-D-glucos-3-OD-glucos-3-0-yl) -D-propyl-acetyl-L-alanyl- pionyl-L-alanyl-D-iso-D-isoglutamine glutamine

1

3rd

1500 jig

Nothing

2nd

3rd

Nothing

1500 jig

3rd

1

Nothing

Nothing

The results were as follows:

(a) All cats in Group 1 vomited 4 to 6 times within 2 to 5 hours after vaccination. The first vomit was a dark liquid, and later the vomit became a clear foam after the

41

636 887

Stomach had been emptied. All animals had diarrhea during the same period. After the initial vomiting and diarrhea, the animals became depressed and neglected. The chin, neck, and front paws were covered with saliva, and the vomit stuck to their mouths 5. If food was offered, it was refused. Rectal temperatures rose to a peak of 40 ° C 7 hours after vaccination. All animals returned to normal 24 hours after vaccination.

(b) All cats in group 2 remain normal after vaccination. They continued to play, climb the walls of the cages, fight and eat normally, and all physiological functions remained normal.

(c) The cat in group 3 (the control group) remained normal throughout the test. is

Example 18

Study of acute toxicity in mice

Protocol: The test substance was dissolved or evenly suspended in an aqueous vehicle which contained 0.9% sodium chloride, 0.5% sodium carboxymethyl cellulose, 0.4% polysorbate-80 and 0.9% benzyl alcohol. The concentration was adjusted so that the stated dose can be administered in a volume of 10 ml per kg of body weight. The test substance was then injected subcutaneously (s.c.) in groups of six male Swiss 25-Webster mice at a dose of 60 mg / kg body weight, and the animals were observed for mortality daily for a period of 21 days. A control group of mice containing no drug was examined at the same time. As can be seen from Table 30 in Table IV, all tested compounds show LD50 values of more than 60 mg per kg body weight. This particular dose was chosen because it is approximately 30 times the dose required to produce increased delayed hypersensitivity and 35 antibody levels in the circulating body fluids as described in the examples.

Example IV

connection

Dose number mg / kg mice

Mode of administration

connection

Dose mg / kg

Number of mice administered

Number of LDso death mg / kg cases SC s.c.

s.c.

s.c.

Blind test 0 6

2- (2-acetamido-2- 60 6 deoxy-D-glucos-3-O-yl) -D-propionyl-L-valyl-D-isoglutamine 2- (2-acetamido-2- 60 6 deoxy-D- glucos-3-O-yl) -D-propionyl-L-leucyl-D-isoglutamine 2- (2-acetamido-2- 60 6 deoxy-D-glucos-3-O-yl) -D-propionyl-La- aminobutyryl-D-iso-glutamine

2- (2-acetamido-2- 60 6 s.c.

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

threonyl-D-isogluta-

min

2- (2-acetamido-2- 60 6 s.c.

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

phenylalanyl-D-iso-

glutamine

45

> 60

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

tyrosyl-D-isoglutamine

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

prolyl-D-isoglutamine

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

hydroxyprolyl-D-iso-

glutamine

2- (2-benzamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

alanyl-D-isoglutamine

2- (2-benzamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

valyl-D-isoglutamine

2- (2-benzamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-propionyl-L-

prolyl-D-isoglutamine

2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl-acetyl-L-acetyl-D-

isoglutamine

2-Acetamido-2-60 deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine

2-Acetamido-2-60 deoxy-D-glucos-3-O-yl-acetyl-L-leucyl-D-isoglutamine

2-acetamido-2-60 deoxy-D-glucos-3-O-yl-acetyl-L-a-amino-butyryl-D-isogluta-

2-acetamido-2-60 deoxy-D-glucos-3-O-

> 60 50 yl-acetyl-L-seryl-D-iso-

glutamine

2-acetamido-2-des- 60 oxy-D-glucos-3-O-yl-

> 60 acetyl-L-threonyl-D-

55 isoglutamine 2-acetamido-2- 60 deoxy-D-glucos-3-O-yl-acetyl-L-phenyl-

> 60 alanyl-D-isoglutamine

60 2-acetamido-2- 60 deoxy-D-glucos-3-O-yl-acetyl-L-tyrosyl ~ D-isoglutamine

> 60 2-Acetamido-2- 60

65 deoxy-D-glucos-3-O-yl-acetyl-L-prolyl-D-isoglutamine s.c s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

Number of LD so mg / kg deaths

1> 60

0> 60

0> 60

0> 60

1> 60

0> 60

0> 60

0> 60

0> 60

1> 60

1> 60

0> 60

0> 60

0 <60

0> 60

636 887

42

connection

Dose mg / kg

Number of mice administered

Number of LD so mg / kg deaths

connection

Dose mg / kg

Number of mice administered

Number of LD so mg / kg deaths

2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl-acetyl-L-hydroxy-

prolyl-D-isoglutamine

2-benzamido-2- 60

deoxy-D-glucos-3-O-

yl-acetyl-L-alanyl-D-

isoglutamine

2-Benzamido-2-60 deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isoglutamine

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-butyryl-L-valyl-

D-isoglutamine

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-butyryl-L-pro-

iyl-D-isoglutamine

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-hexanoyl-L-

valyl-D-isoglutamine

2- (2-acetamido-2- 60

deoxy-D-glucos-3-O-

yl) -D-hexanoyl-L-

prolyl-D-isoglutamine s.c s.c.

s.c.

s.c.

s.c.

s.c.

s.c.

> 60. 2- (2-acetamido-4,6-60

di-O-acetyl-2-deoxy

D-glucos-3-0-yl) -D-

propionyl-L-alanyl

> 60 io D-isoglutamine

2- (2-acetamido-4,6-60

di-O-acetyl-2-deoxy

D-glucos-3-0-yl) -D-

> 60 propionyl-L-valyl-D-

15 isoglutamine

2- (2-acetamido-4,6-60 di-O-acetyl-2-deoxy-

> 60 D-glucos-3-0-yl) -D-

propionyl-L-prolyl-D-20 isoglutamine

2-acetamido-4,6-di-60

> 60 O-acetyl-2-deoxy-D-

glucos-3-O-yl-acetyl-L-alanyl-D-isogluta-25 min

> 60 2-acetamido-4,6-di-60

O-acetyl-2-deoxy-D-glucos-3-O-yl-acetyl-L-valyl-D-isogluta-

> 60 30 min s.c.

s.c.

s.c.

s.c.

s.c.

> 60

> 60

> 60

> 60

> 60

Claims (13)

636 887 PATENT CLAIMS 1. Process for the preparation of new compounds of the formula: hcor (Ï) in which R and R1 are identical or different and each represent hydrogen or an aryl radical having 1 to 22 carbon atoms, R2 is an optionally substituted alkyl radical having 1 to 21 carbon atoms or an optionally substituted aryl radical having 6 to 10 carbon atoms, R6 is hydrogen or an alkyl radical having 1 up to 16 carbon atoms, X means one of the following aminoacyl groups: glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-ami-nobutyryl, L-seryl, L-threonyl, L-methionyl, L- Cysteinyl, L-phenylalanyl, L-tyrosyl, L-tryptophanyl, L-lysyl, L-ornithylyl, L-glutamyl, L-glutaminyl, L-asparagyl, L-asparaginyl, L-prolyl and L-hydroxyprolyl; Y represents one of the amino acid residues D-isoasparagine and D-isoglutamine and the wavy lines mean the a or β configuration or mixtures thereof, where if one wavy line means a, the other means β, and further if R and R1 both are hydrogen, R2 is methyl or hydroxymethyl and R6 is methyl, X is not glycyl, L-alanyl or L-seryl, characterized in that the benzyl ether, benzyl thioether, benzylidene acetal and benzyl ester groups from a corresponding compound of Formula: R "0 r -ch-co-x -nh-chconh cooch2c6h5 (ii) wherein R2 and R6 have the above meanings, n represents 1 or 2, X1 glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl, O-benzyl-L-seryl, O-benzyl -L-threonyl, L-methionyl, S-benzyl-I ^ cysteinyl, L-phenylalanyl, O-benzyl-L-tyrosyl, L-tryptophanyl, e-carbobenzyloxy-L-lysyl, 5-carbo- benzyloxy-L-ornithyl, the y-benzyl ester of L-glutamyl, L-glutaminyl, the β-benzyl ester of L-asparagyl, L-asparaginyl, L-prolyl or O-benzyl-L-hydroxyprolyl and R 'and R ", which are identical or different, each represent an acyl radical having 1 to 22 carbon atoms or one of the symbols R 'and R" represents an acyl radical having 1 to 22 carbon atoms and the other is hydrogen or R' and R "together represent a benzylidene acetal group, cleaved by catalytic hydrogenolysis. 2. The method according to claim 1, characterized in that R6 is hydrogen. 3. The method according to claim 1, characterized in that R6 is methyl. 4. The method according to claim 1, characterized in that R and R1 both represent hydrogen. 5. The method according to claim 1, characterized in that R2 is an unsubstituted alkyl radical having 1 to 22 carbon atoms. 6. The method according to claim 1, characterized in that R and R1 are the same acyl radical having 1 to 22 carbon atoms. 7. The method according to claim 1, characterized in that Y is D-isoglutamine. 8. The method according to claim 1, characterized in that R2 is methyl. 9. The method according to claim 1, characterized in that R2 means hydroxymethyl. 10. The method according to claim 1, characterized in that R, R1, R ', R ", R2, R6, X, Y and X1 have the same meanings as in claim 1, wherein X is not glycyl, L-alanyl or L- Is seryl and X1 is not glycyl, L-alanyl or O-benzyl-L-seryl when R and R1 are both hydrogen, R2 is methyl or hydroxymethyl and R6 is methyl. 11. The method according to claim 1, characterized in that R, R1, R ', R ", R2, R6, X, Y and X1 have the same meanings as in claim 1, wherein X is not glycyl, L-alanyl or L- Is seryl and X1 is not glycyl, L-alanyl or O-benzyl-L-seryl when R and R1 are both hydrogen, R2 is methyl or hydroxymethyl and R6 is methyl, and wherein: (i) X is not glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl or L-seryl and X1 is not glycyl, L-alanyl, L-valyl, L-leucyl, L- Isoleucyl, La-aminobutyryl or O-benzyl-L-seryl when R6 is hydrogen or alkyl having 2 to 7 carbon atoms and Y is D-isoglutamine, and / or (ii) R2 is unsubstituted methyl or a substituted methyl group with 1 carbon atom when R6 is methyl, Y is D-isoglutamine, X is glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl or L -Seryl means and X1 means glycyl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl or O-benzyl-L-seryl. 12. The method according to claim 1, characterized in that R6 is hydrogen, X is one of the aminoacyl radicals L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl, L-seryl, L-threonyl, L-tryptophanyl , L-lysyl, L-ornithyl, L-glutamyl, L-glutaminyl, L-methionyl, L-cysteinyl, L-phenylalanyl, L-tyrosyl, L-asparagyl, L-asparaginyl, L-prolyl and L-hydroxyprolyl and X1 means L-alanyl, L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl, O-benzyl-L-seryl, O-benzyl-L-threonyl, L-methionyl, S-benzyl-L-cysteinyl , L-phenylalanyl, O-benzyl-L-tyrosyl, L-tryptophanyl, s-carbobenzyloxy-L-lysyl, 8-carbobenzyloxy-L-ornithyl, the y-benzyl ester of L-glutamyl, L-glutaminyl, the ß-benzyl ester of L-asparagyl, L-asparaginyl, L-prolyl or O-benzyl-L-hydroxyprolyl. 13. The method according to claim 1, characterized in that R6 is an alkyl radical having 1 to 4 carbon atoms, X is a 2nd 5 10th 15 20th 25th 30th 35 40 45 50 55 60 6? 636 887 the aminoacyl residues L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl, L-threonyl, L-tryptophanyl, L-lysyl, L-ornithyl, L-glutamyl, L-glutaminyl, L-methionyl, L-cysteinyl, L-phenylalanyl, L-tyrosyl, L-asparagyl, L-asparaginyl, L-prolyl and L-hydroxyprolyl and X1 denotes L-valyl, L-leucyl, L-isoleucyl, La-aminobutyryl, O-benzyl-L-threonyl, L-methionyl, S-benzyl-L-cysteinyl, L-phenylalanyl, O-benzyl-L-tyrosyl, LT ryptophanyl, e-carbobenzyloxy-L-lysyl, ô-carbobenzyloxy-L-ornithyl, the y-benzyl ester of L- Glutamyl, L-glutaminyl, the β-benzyl ester of L-asparagyl, L-asparaginyl, L-propyl or O-benzyl-L-hydroxyprolyl.