FI66878C - FOERFARANDE FOER FRAMSTAELLNING AV NYA ANTIGENDERIVAT - Google Patents

Description

ΓηΊ Μ4 \ ANNOUNCEMENT ,, ηΠΟ jSSTa m ου uTLÄCGNiNGssumiFT 6 68 / o (51) K * .lfc / lm.Ct3 C 07 G 7/00, A 6l K 39/00 FINLAND — FINLAND (21) r ** «tm .k.nw-p «Mnt» n. & fcnifl * 79058 ^ + Ρ, Η - »*» - 21.02.79 v / (23) Alkupthrt — Gl (tfgh «t» d * j 21.02.79 (41) Tulta Publication - MlvM offumNf 2 5.08.79

Patent and Registration Office (44) ΝίΜΜΜρνιοη | a moonL | iillaiMn p * m.—? i q8.84

Patent- och f ^ iltintjfFlIilll Amttkan (iCkfd odt utLikrlfUA pubHcwvtf (32) (33) (31) I · χτ <· «Τ« wellww — t * | M prtorHet 24.02.78 07.04.78, 18.05.78 Switzerland-Switzerland ( CH) 2035 / 78-0, 3777 / 78-5, 5394 / 78-0 (71) Ciba-Geigy AG, CH-4002 Basel, Switzerland-Switzerland (CH) (72) Gerhard Baschang, Bettingen, Felix M. Dietrich , Basel,

Roland Gisler, Binningen, Jaroslav Stanek, Birsfelden, Switzerland-Switzerland (CH), Albert Hartmann, Grenzach, Lajos Tarcsay, Grenzach-Wyhlen,

Federal Republic of Germany1ta-FÖrbundsrepubliken Tyskland (DE) (74) Oy Jalo Ant-Wuor i nen Ab (54) Method for the preparation of new antigen derivatives -Förfarande för framstä11 Ning av nya antigenderivat

The invention relates to a process for the preparation of novel antigen derivatives consisting of an antigen to which at least one and at most as many muramyl peptide molecules are bound per antigen molecule that the antigenic nature is retained, and optionally bridging members and a carrier, the unbonded muramyl peptide having the structure CH2OR6 / N - X - R2 (II) R3 - CH (D) R13 R8 R10 R11 CON - CH - CON - CH - CHOCH - R. 0 1 <ö t (D) R7 R9 2 66878 wherein X is a carbonyl or carbonyloxy group , R 1, R 2 and R 8 are independently hydrogen or trimethylsilyl, R 2 is a phenyl residue or unsubstituted or lower alkyl substituted by hydroxy, carboxy, lower alkoxy and / or lower alkoxycarbonyl,

R 9, R 2, R 8 and R 2 are independently hydrogen or lower alkyl, R 8 is hydrogen, phenyl residue or unsubstituted or substituted by hydroxy, halogen, amino, mercapto or phenyl residue lower alkyl, or R 1 and R 8 together are alkylene having 3 or 4 carbon atom, and R 10, R 11 and R 12 are independently carboxy, trimethylsilyloxycarbonyl, unsubstituted or phenyl-substituted lower alkoxycarbonyl, or carbamoyl which is unsubstituted or substituted on the nitrogen atom by carboxy or allyloxy or allylcarboxy, lower 1 is also hydrogen, provided that at least one free hydroxy, amino, mercapto or carboxy group is present in the starting compound of formula II.

These novel antigen derivatives are thus compounds consisting of an antigen and at least one muramyl peptide having the above-mentioned structure, covalently bound to it by a bridge member. These new antigen derivatives can be described in more detail, for example, by the formula A '[Z °' 1 J ° (1)

It has an A antigen residue, Z a bridge member (Spacer), MP a residue of the above muramyl peptide, and n is an integer greater than 0.

In this case, an antigen is understood to mean an organic substance whose physiological medium, i.e. from human or animal organs, is recognized as immunologically foreign or can be identified as foreign under suitable conditions.

Antigens primarily include any agent that elicits living specific immunity to infectious pathogens 3 66878 or adverse reactions such as allergic sensitization or rejection of transplanted foreign tissue. In particular, these include antigens as components of vaccines.

On the other hand, vaccines are those which can be used in a classical vaccination method to provide specific immunological protection against infectious diseases. Suitable antigens for such vaccines are attenuated living or dead, modified or degraded infectious agents, toxoids formed from these pathogens, or naturally or synthetically produced subcomponents of the pathogen and toxoids. The categories of pathogens to be mentioned are, in particular: viruses, chlamydia, raccoons, bacteria, protozoa or matso parasites. Preferred antigens are those suitable as components of vaccines for the treatment of e.g. influenza A and B, parainfluenza 1-3, respiratory syncytial virus, rhinovirus or adenovirus respiratory diseases, cytomegaly, rubella, measles, swine fever whooping cough, poliomyelitis, Herpes simplex 1 or 2, chickenpox and shingles, rotavirus diseases, hepatitis A, B and others, rabies, foot-and-mouth disease, trachoma, osteoporosis, madococci A, B and C meningitis, pneumococci, H.influenzae'11a, streptococci (especially rheumatic fever), Psodomonas1 Elia and Proteus, typhus, paratyphoid and other enterobacterial diarrheal diseases, gonorrhea, gonorrhea, syphilis sleep diseases and Chagas disease), leishmaniasis, tapeworm disease, split worm disease, hookworm disease and other worm diseases.

On the other hand, mention should be made of new types of vaccines which are not directed against infectious agents, but either against body-specific constituents, i.e. normal and abnormal autoantigens, or against sensitizing environmental antigens, i.e. allergens.

In some cases, immunization against normal and aberrant autoantigens is intended to trigger the functions of body-specific molecules (e.g., hormones, other neurotransmitters, and humoral and cellular receptors) or the proliferation or continuity of aberrant, particularly neoplastic cell lines. Preferred antigens as components of such vaccines include, for example, human chorionic gonadotropin subsequences or sperm components for immunization against fertility mediators and thus for immunological inhibition of reproductive functions; mediators of the inflammatory phenomenon, in particular in purified form, e.g. lymphokines isolated from lymphocytes, in particular for the immunological prevention of macrophage Migration Inhibitor Factor (MIF) inflammatory diseases; immunologically specific antigen receptors for lymphocytes and antibodies (fractionated, antigen-specific lymphocytes, antigen receptors extracted or isolated from these lymphocytes, fractionated antigen-specific antibodies to anti-antigen-specific antigens) for anti-idiotypic immunization to eliminate pathogenic immune processes such as autoimmunity (eg against synovial antigen and immunoglobulins in primary chronic polyarthritis, anti-myelin components in in allergies (eg, hay pollen, dust, or medications for allergic asthma a, in allergic rhinitis or drug hypersensitivity) or as such to avoid normal but undesired immune reactions (e.g. to induce immune tolerances to prevent rejection of transplanted foreign organs and tissues); autologous or cross-reacted homologous or heterologous tumor cells, tumor cell fragments or membrane components, including oncornavirus-encoded glycoproteins such as GP 70, for tumor-specific immunization in the prevention and treatment of cancer.

In other cases, immunization against allergens has sought to induce pathogenetically, instead of the relevant IgE antibody response, primarily or to a sufficient extent against environmental antigens sensitizing IgG and IgA antibodies, thereby capturing allergens in the circulation and secretions with specific antibodies before they can react. (Mastzelle) bound IgE antibodies and thus trigger the release of allergic mediators. In this antigen-specific desensitization, 66878 5 sa are the allergens themselves, i.e. e.g. hay pollen, dust or drug, as an antigenic component of the vaccine.

Antigens, especially when they are small molecules, may also be completely and preferably covalently bound to a high molecular weight carrier. As the carrier, mention may be made in particular of lactic acid polymers and their derivatives having a free carboxyl group at the chain end, such as their esters with glycolic acids, polylactic acid amides or lactic acid polyesteramides, as disclosed, for example, in -methylcellulose or agarose. Further suitable carriers are basic, neutral or acidic polyamino acids which are not themselves immunogens, such as polyaspartic acid, polyglutamic acid, polylysine or polyornithine. Any other antigens within the meaning of the above definition or the examples given are also suitable as carriers, provided that an immune response against them is possible or even desirable. Thus, for example, the HCG peptide may be covalently bound to the tetanus toxoid, as a carrier.

The various moieties of the novel compounds are covalently linked to each other, i.e., the antigen is bound in at least one of its functional groups in peptide chemistry by conventional attachment to a muramyl peptide residue, directly or via a bridging member (Spacer).

Particularly suitable bridging members (Spacer) are bivalent residues of aliphatic compounds, e.g. residues of compounds having at least two amino groups, at least one amino group and one carboxy or thiocarboxy group, or at least two carboxy or thiocarboxy groups, such as aliphatic diamines, amino-thiocarboxylic acids , neutral, basic or acidic aliphatic amino acids di- or oligopeptides.

As the bridging member, mention should be made in particular of α, ω-diaminoalkanes, in particular α, ω-diaminoower alkanes, such as ethylenediamine, propylene diamine, tetramethylenediamine, alkyl dicarboxylic acids, such as α-succinic acid or glutaric acid, α, β or γ-aminoalkane lower alkanecarboxylic acids, especially natural α-amino-lower alkanecarboxylic acids such as glycine, β-alanine, L-alanine, α-aminoisobutyric acid, valine or leucine.

6 66878

Mention may be made, in particular, of carboxylic acid ester, carboxylic acid amide, thiocarboxylic acid ester or thiocarboxylic acid amide groups as covalent connecting elements.

Said new compounds may contain several covalent connecting elements, depending on the nature of the bridging member always used. Thus, for example, the above formula I may be in the following more detailed form

f A “I

Jjj en I - [r · - * ·· '] ^ - * ·· -, ^ <m) LIJ 0-1 m * - \ hi _LT Jo-i where A is the antigen residue, T is the carrier residue, MP is a residue of mura-myyl peptide, Z 'and Z "are bivalent bridging members, and X', X", X '"and X1V are covalent linkers and m and n are integers greater than 0.

Alkyl is straight-chain or branched, optionally bonded alkyl having up to 18 carbon atoms, however, preferably lower alkyl.

A substituted alkyl residue, such as a lower alkyl residue, may contain one, two or more identical or different substituents.

In the context of this specification and claims, residues and compounds with the word "lower" preferably contain up to 7, and preferably up to 4 carbon atoms.

In the foregoing and in the following, the general terms may have the following meanings:

Lower alkyl is, for example, n-propyl, n-butyl, isobutyl, sec-butyl or tert-butyl, also n-pentyl, n-hexyl, isohexyl or n-heptyl and preferably methyl or ethyl. In phenyl-lower alkyl, the lower alkyl residue is especially methyl or ethyl.

Lower alkoxy is, for example, n-propoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy and preferably methoxy or ethoxy.

Lower alkanoyl is in particular propionyl or butyryl, but is primarily acetyl.

The novel antigen derivatives may be in the form of mixtures of isomers or in the form of pure isomers.

It is known that muramyl peptides are good excipients which, when properly mixed with antigens, can contain their immunogenicity. However, it has been found that they have only a short-term effect because they are excreted relatively quickly from the human or animal body. In particular, they are only able to induce cell-mediated immunity in vivo against soluble antigens under certain conditions unsuitable for clinical purposes, namely in mixtures with antigens in a mineral oil emulsion.

The novel compounds of this invention now elicit a marked enhancement of the immune response in the antigen, in particular also cell-mediated immunity under clinically acceptable dosing conditions, as shown by the following experimental arrangements: 1. Enhancement of cell-mediated immunity in vivo:

Increased delayed hypersensitivity to bovine serum albumin (BSA) and sheep erythrocytes (SRBC) in guinea pigs.

Pirbright guinea pigs are immunized on day 0 with 1 mg of BSA or 1 mg of SRBC ghost cells ("SRBCG") in complete Freund's adjuvant · by injecting 0.1 mg of antigen adjuvant mixture into each hindpaw each time. 3 weeks later, skin reactions are triggered by subcutaneous injection of 100 μg BSA or resp. 100 μg of SRBCG dissolved in 0.1 ml of buffered saline and after 24 hours the reaction intensity is obtained based on the area of reddening rash and the increase in skin thickness. The antigen-specific increase in reaction intensity observed after 24 hours (delayed reaction) is considered a measure of cell-mediated immunity.

BSA and SRBCG are too weak immunogens to induce a delayed reaction alone or as a water-in-oil emulsion with incomplete Freund's adjuvant (10 parts BSA solution, respectively RSNCG suspension in 0.9% NaCl mixed with 8.5 parts Bayol F: (paraffin oil, petroleum hydrocarbon fraction) and 1.5 parts Arlacel A (mannitan monooleate)), but for effective immunization they must be used in a complete vehicle supplemented with mycobacteria (5 mg dead and lyophilized M. butyricum '). ia / 10 ml Bayol F / Arlacel A).

8 66878

Instead of mycobacteria, new compounds are used which contain BSA as antigen (1 mg BSA, 60 μg MDP / animal) or SRBCG as antigen (1 mg SRBCG, 25 μg MDP / animal), either as an antigen-oil mixture or suspended in carboxymethylcellulose ( CMC). The new compounds induced a delayed reaction in the absence of mycobacteria in the experimental set-up described above.

Significant enhancement of delayed reactivity against BSA and SRBCG can also be achieved by not combining new compounds with incomplete Freund's adjuvant but by administering them suspended in CMC. Intramuscular administration has proven to be particularly effective in this case. Under these conditions, an equal amount of free muramyl peptide mixed in the CMC mixture was substantially less active than the new active ingredient. Thus, it was shown that the novel compounds under clinically acceptable dosing conditions, i.e., when co-administered with body-friendly additives, can induce cell-mediated immunity even against soluble protein antigen.

2. Enhancement of cell-mediated immunity in vivo:

Enhancement of delayed hypersensitivity to BSA and SRBCG in mice.

MAG dog mice were immunized on day 0 with gradual doses of antigen (BSA agarose or SRBCG) that had not been conjugated to muramyl peptide or antigens conjugated to muramyl peptide (BSA agarose or SRBCG). BSA agarose preparations were administered subcutaneously at a dose of 0.1-100 μg (corresponding to a dose of 0.0029-6 μg of active compound with the new compounds together with muramyl peptides per animal) in a volume of 0.2 ml of buffered saline. SRBCG preparations were administered intraperitoneally at a dose of 0.01 to 3 mg (corresponding to a dose of 0.25 to 75 μg of the active compounds with the new compounds together with muramyl peptides per animal) in a volume of 0.5 ml of buffered saline and 0.05 ml, respectively. in a volume of 1 ml intradermally divided into three paws.

4 to 20 days later, delayed reactions are triggered by injection

Q

by acting on the left hind paw, 100 ug of BSA, 10 SRBCs in 20 ul of buffered saline, and after 24 and 48 hours, the reaction intensity is determined on the basis of paw swelling. The observed antigen-specific increase in paw volume is considered a measure of cell-mediated immunity.

Starting from day 14 of immunization with BSA-agarose-MDP compounds, there were also already significantly lower doses of 0.1 μg; corresponding to 0.006 μg of active substance) clear delayed reactions. In contrast, free BSA agarose is unable to sensitize delayed reactions. Likewise, SRBCG-MDP compounds, especially when administered intradermally, are capable of inducing a delayed reactivity that is significantly more pronounced than that which can be obtained by sensitization with SRBCG not bound to muramyl peptide.

Thus, it has also been shown that the novel compounds can significantly enhance cellular immunity.

3. Enhancing humoral immunity in vivo:

Elevation of antibody production against BSA in mice.

NMR1 mice were immunized intraperitoneally by injecting 0.1-100 μg BSA bound to muramyl peptide (0.0014-6.0 μg active ingredient) on day 0, 10, 17 and 28 days later, serum samples were taken and tested for anti-BSA antibody. concentration by passive haemagglutination technique. At the doses used, free BSA is subimmunogenic in the recipient animals, i.e. it is not able to produce any kind of antibody or only produces very insignificant antibody production. A compound with BSA in combination with muramyl peptide allows a 2-3-fold increase in serum antibody titer (log2 titer sum of titer differences on three days of blood test). It is also noteworthy that the novel compounds, which were further coupled to agarose as a carrier, are even more potent immunogens when administered intraperitoneally or subcutaneously.

This experiment showed that the novel compounds of the invention can also significantly enhance humoral immunity.

The new antigen derivatives are novel or improved known vaccines and can be used in novel vaccination methods or to simplify useful vaccination methods (whereby, for example, the number of vaccinations required to maintain longer-term protection can be reduced).

In particular, the invention relates to a process for the preparation of novel antigen derivatives containing antigen as a component of vaccines against parasites, bacteria, viruses, tumor cells, physiological constituents, their modified forms or subunits thereof, optionally covalently bound via bridge members, where R1, Rg, R4 # Rg and R? are hydrogen, X is carbonyl and R 2 is lower alkyl or phenyl optionally substituted by hydroxy or lower alkoxy and R 9, R 8, R 10, R 11, R 12 and R 13 are as defined above.

In particular, the invention relates to a process for the preparation of novel antigen derivatives containing antigen against parasites, bacteria, viruses, tumor cells, physiological constituents of the body, their modified forms or their subunits, optionally covalently bound via bridges to R 4, muramyl R 1 is hydrogen, X is carbonyl, R 2 is lower alkyl or phenyl optionally substituted by hydroxy or lower alkoxy, and R 3 is methyl and R 8, R 8, R 10 and R 13a R 3a are as defined above.

The invention relates in particular to a process for the preparation of novel antigenic derivatives containing covalently bonded muramyl peptides of the formula II in which R 1, R 4, R 8 and R 3 are hydrogen, X is carbonyl, R 2 is optionally substituted by hydroxy or nitroxy lower alkyl or phenyl, R 8 is hydrogen or methyl , R 7 and R 8 are hydrogen, R 8 is lower alkyl, hydroxy lower alkyl or phenyl and R 1, R 6 and R 8 are carboxyl, lower alkoxycarbonyl or carbamoyl and R 6 is also hydrogen.

In particular, the invention relates to a process for the preparation of novel antigenic derivatives containing covalently linked muramyl peptides of the formula II in which R 1, R 4, R 8 and R 3 are hydrogen, X is carbonyl, R 2 is optionally substituted by hydroxy or nitroxy lower alkyl or phenyl, R 8 and R 8 are hydrogen or methyl, R 9 is methyl, ethyl, n-propyl, i-propyl, 2-methylpropyl, hydroxymethyl, hydroxyethyl or phenyl and R 10, R 1 and R 12 are carboxy, lower alkoxycarbonyl or carbamoyl, R 1 is also hydrogen.

The invention also relates to a process for the preparation of novel antigen derivatives containing the antigen as components of vaccines against bacteria, viruses, 1 66678 tumor cells, physiological constituents, their modified forms or their subunits, optionally covalently linked via a bridging member to R R 1, R 8 and R 8 are hydrogen, X is carbonyl, R 1 and R 8 together are propylene or butylene and R 6, R 2, R 2, R 10, R 11 and R 12 are as defined above.

The bridge members in the above definitions are in particular α,,-diamino-lower alkanes, lower alkyl-dicarboxylic acids, natural α-amino-lower alkanecarboxylic acids.

In particular, the invention relates to a process for the preparation of the novel antigen derivatives exemplified.

The new compounds can be prepared by methods known per se.

The process for the preparation of novel antigen derivatives according to the invention is characterized in that the antigen optionally linked to the bridging members is condensed by covalent bonding with oxycarbonyl, iminocarbonyl or carbonylthio groups, optionally to the bridging members with at least one of the muramyl peptides of formula II, - and / or a mercapto group, and on the other at least one carboxylic acid group, and the compound obtained as described above, if desired, is also condensed by forming covalent bonds with oxycarbonyl, iminocarbonyl or carbonylthio groups on a carrier which may be bonded to bridging members.

The condensations are then carried out, for example, by reacting a compound in the form of an activated carboxylic acid with another compound in the form of a free amino, hydroxy or mercapto compound. The activated carboxyl group may be, for example, an acid anhydride, preferably an acid azide, an acid amide such as imidazolide, isooxazolid or an activated ester. Activated esters include, in particular, cyanomethyl ester, carboxymethyl ester, p-nitrophenylthioester, methoxyethylthioester, acetylaminoethylthioester, p-nitrophenyl ester, 2,4,5-trichlorophenyl ester, N-hydroxysuccinimide ester, N-hydride -hydroksipiperidiiniesteri. The active esters can also be obtained optionally from carbodiimide N-hydroxysuccinimide or unsubstituted or e.g. 1-hydroxybenzotriazole or 3-hydroxy-4-oxo-3,4-dihydrobenzo (d-hydroxybenzotriazole) substituted by halogen, methyl or nitro ) With -1,2,4-triazine.

The removal groups used in these condensations must be non-toxic or highly removable to avoid the most molecular compounds retaining toxic moieties by adsorption.

Therefore, as active esters, those obtained by N-hydroxysuccinimide or its C-substitution products, such as N-hydroxymethyl or dimethyl succinimide, or by reaction with a carbodiimide, such as carbodiimide itself or 1-ethyl-3- (3-dimethylimide), are preferred. with ethylaminopropyl) -carbodiimide.

The above reaction is carried out in a conventional manner either without or in the presence of diluents, condensation and / or catalytic agents, if necessary at reduced or elevated temperature. Preferably, work is done to prevent antigens from being destroyed, in an aqueous medium and in the pH range of 6-9, primarily in the pH range of 7-8.

The invention also relates to embodiments of the processes in which the reaction component is optionally in the form of its derivatives, such as a salt and / or in the form of mixtures of isomers or pure isomers.

Suitably, the starting materials used for carrying out the condensations according to the invention are those which initially lead to particularly desirable groups of end products and, above all, to the end products which are specifically shown and preferred.

The starting materials used are known or, if new, can be prepared by methods known per se.

The novel antigen derivatives according to the invention can also be used as pharmaceutical preparations. The pharmaceutical preparations according to the invention are those which are administered to warm-blooded animals enterally, such as orally or rectally, as well as parenterally, and which contain the pharmacologically active substance alone or in combination with a pharmaceutically acceptable carrier.

The novel pharmaceutical preparations contain from about 10% to about 95%, preferably from about 10% to about 90%, of the active ingredient. The pharmaceutical preparations according to the invention are in unit dosage forms, such as granules, tablets, capsules, suppositories or ampoules.

The preferred form of use consists of a solution or suspension of the new antigen derivatives, preferably containing up to 10% by weight of carboxymethylcellulose.

13 6687 B

Thus, the novel vaccines are used in known vaccination methods in approved or known dosages, respectively, in weight or international units, e.g., antigen derivatives containing early germ cells are administered in doses containing 10 to 10 cytological organisms at intervals of 1 to 8 weeks. In this case, it is preferred that each mg of protein contains 5 to 200 micrograms of muramyl peptide.

Preferably, for immunization with soluble compounds, an equivalent amount of antigen derivative in Falz solution (BSS) containing 0.14 g of calcium chloride, 0.8 g of saline, 0.2 g of magnesium sulfate -71 ^ 0, 0.2 g of magnesium chloride * 61 ^ 0, 0.6 g of potassium dihydrogen phosphate and 0.24 g of disodium hydrogen phosphate * 21 ^ 0 per liter of water.

If a depetitive effect is sought (e.g. topical, intradermal or intramolecular dosing), carboxymethylcellulose (preferably a final concentration of 5%) can be added to the antigen derivative thus dissolved.

Insoluble Macromolecular antigen derivatives are preferably administered as suspensions in BSS using carboxymethylcellulose as a stabilizer (preferably a final concentration of 5%). To prepare a stable suspension, the ice-cooled mixture is preferably sonicated in a concentrated manner.

Antigel derivatives with cells are administered primarily in a tissue culture medium particularly suitable for each cell type (e.g., EAGLE'S high amino acid medium for lymphocytes) (click et al., Cell. Immunol, Vol. 3, pp. 264-276 (1972)).

The novel muramyl peptides of formula II used as starting materials, in which X is a carbonyl group and R 9 are independently hydrogen, at least one of the radicals R 1, R 8 and R 4 is lower alkyl, preferably methyl and the others are hydrogen, and other substituents the supports have the meanings given above, can be prepared by condensing in a manner known per se a compound of the formula IV of 14 66878 CHOOR? J— \ K Λ> ^ 0 'R1 (IV> _ // y -x - r2

R 1 - CH (D) R

\

COOH

wherein X, R 2, and R 2 are as defined above and R 0, R 0 and R 0 are the radicals R 1, R 4 or R 8 or a readily cleavable protecting group, or a derivative thereof with a compound of formula V

R ° R0 rO

, 8, 10, 11 HN - CH - CON - CHCH 2 CH - R ° (V) r 7 (1) r 9 where R 0, R 0 Q, and R 0 2 have the same meaning as R g, R 1 and R 2; provided that the carboxy and, if desired, free hydroxyl groups present in these residues are protected by easily removable protecting groups, and optionally by cleavage of the protecting groups present.

The condensation is then carried out, for example, by reacting a compound of the formula IV in the form of an activated carboxylic acid with an amino compound of the formula V, or by reacting an acid of the formula IV with a compound of the formula V having an amino group in the activated form. The activated carboxyl group may be, for example, an acid anhydride, preferably a mixed acid anhydride such as an acid azide, an acid amide such as imidazole, an isooxazolid or an activated ester. Activated esters which may be mentioned are, in particular, cyanomethyl ester, carboxymethyl ester, p-nitrophenylthioester, p-nitrophenyl ester, 2,4,5-trichlorophenyl ester, pantachlorophenyl ester, N-hydroxysuccinimide ester, N-hydroxyphthalimide ester, 8-hydroxy -dihydro-1-carboethoxy-quinoline ester, N-hydroxypiperidine ester or enol ester obtained with N-ethyl-5-phenyl-isooxazolium 3'-sulfate. Activated esters can also be obtained, optionally with carbodiimide, by the addition of N-hydroxysuccinimide or unsubstituted or, e.g., halogen, methyl or nitro-substituted 1-hydroxybenzotriazole, 3-hydroxy-4-oxo-3,4-dihydrobenzo ( d) 1,2,3-tri-azines.

The amino group is activated, e.g., by reaction with phosphite amide.

Of the processes for the reaction with an activated ester, special mention should be made of the reactions with N-ethyl-5-phenyl-isooxazolium 3'-sulfonate (Woodward reagent K) or 2-ethoxy-1,2-dihydro-1-carboethoxy. -quinoline or carbodiimide.

Easily cleavable protecting groups are those known in peptide or sugar chemistry. Mention may be made, in particular, for carboxy groups, tert-butyl, benzyl or benzhydryl, and for hydroxy groups, in particular acyl radicals, e.g. lower alkanoyl radicals, such as acetyl, aroyl radicals, such as benzoyl and, in particular, carbonyl-derived radicals, .-butyl, benzyl or tetrahydropyranyl optionally substituted by nitro, lower alkoxy or halogen or optionally substituted alkylidene residues which bind the oxygen atoms in the 4- and 6-positions. Such alkylidene residues are in particular a lower alkylidene residue, in particular an ethylidene, isopropylidene or propylidene residue or also an optionally substituted benzylidene residue, preferably substituted in the p-position.

These protecting groups can be cleaved off in a manner known per se. They can be removed hydrogenolytically, e.g. with hydrogen in the presence of a noble metal such as palladium or platinum catalyst.

The starting materials used are known or can be prepared in a manner known per se.

The novel muramyl peptides of formula II used as starting materials, in which X is a carbonyl group, R1, R4 and R8 are trialempkylsilyl, preferably trimethylsilyl, and the other substituents have the meanings given above, can be obtained by reacting a compound of formula XI in a known manner.

CH 2 OH

/ ~ °> HM — r / N - X - R2 <XI) R3 - CH (D) R13 \ i8 i10 iu CON - CH - CON - CH - CHOCH - R, „I r 2 12

R (L> R

R7 · R9 to react with a reactive ester of a tri-lower alkylsilyl compound.

as the reactive esters of the tri-lower alkylsilyl compound, mention may be made in particular of trialperkylsilyl halides, in particular chlorides or bromides, bis-loweralkylsilylacetamide or sulphamide.

The reaction is preferably carried out in a solvent that does not contain reactive hydroxy or amino groups, such as dimethylformamide, dioxane, tetrahydrofuran, dimethoxyethane or chloroform.

The following examples illustrate the above invention; temperatures are given in degrees Celsius.

Example 1:

To a solution of 1 g of bovine serum albumin in 100 ml of 0.1 M sodium hydrogen carbonate-0.5M saline solution is added, with stirring, 500 mg of 1-acetamido-3-O - {(L-1- (D-1-carbamoyl-3- succinimido-oxycarbonyl-propyl) carbamoyl-ethyl) -carbamoyl-methyl-yl} -2-deoxy-D-glucose. The solution is stirred for 4 hours at room temperature and then sterile filtered (MF-Millipore, 0.45 filter). The conjugated bovine serum albumin is separated from the low molecular weight reaction products or salts by a diafiltration method using an Amikon UM-10 filter (ultrafiltration membrane with a nominal resolution of 10,000 Daltons, manufactured by Amicon Corp.) and lyophilized.

Quantitative determination of muramyl peptide bound to bovine serum albumin is performed by the Morgan-Elson reaction according to the application of J.M. Ghuysen et al. (Methods in Enzymology 8, (1966) 629). On average, 60 μg of muramyl lipeptide was found to bind to 1 mg of bovine serum albumin compound.

The succinimido ester used as starting material is prepared, for example, as follows: 1 mmol of 2-acetamido-3-O - {(L1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy- D-Gluose, 1 mmol of dicyclohexylcarbodiimide and 1.1 mmol of N-hydroxysuccinimide are dissolved in 3 ml of absolute dimethylformamide and stirred for 20 hours in a sealed vessel, protected from moisture. The precipitated dicyclohexylurea is separated off, the solvent is evaporated off under high vacuum and the residue is taken up in ether, then filtered off with suction and dried. The succinimido oxyester thus obtained can be stored protected from moisture, e.g. in a nitrogen ampoule. Example 2:

Condensation of the antigen derivative prepared in Example 1 with activated agarose; in this case a commercially available agarose derivative of BIO-RAD, Affi-Gel 10, is used. It contains in the agarose backbone the ether side chains ("Spacer arms") of N-alkyl succinamides esterified with N-hydroxysuccinimide.

Dissolve 120 mg of the bovine serum albumin derivative prepared according to Example 1 in 1.25 ml of 0.1 M phosphate buffer, pH 7.3, at 4 °. 500 mg of Affi-Gel 10 is then suspended in the solution by shaking and shaken for a further 4 hours at 4 °. The remaining active ester groups are converted by treatment with 1 M ethanolamine.HCl-0.1 M phosphate buffer solution (pH 7.3) for 30 minutes. The column is then filled with gel and washed first with 200 ml of 0.1 M phosphate buffer-1 M saline (pH 7.3), then with 20 ml of physiological saline.

The determination of Affi-Gel 10: precondensed bovine serum albumin-muramyl lipid peptide compounds is performed by quantitative analysis of the appropriate bovine serum albumin amino acids in the total hydrolysis of the determined gel samples. On average, 9.10 mg of bovine serum albumin muramyl peptide derivative binds to 1 mg of swollen Affi-Gel 10.

Example 3:

Sheep erythrocyte membrane is obtained from fresh sheep blood by the method of Dodge, J.I. et al. (Arch, Biochem. Biophys. 100 (1963) pp. 114-180). To a suspension of 500 mg of sheep 66878 18-head erythrocyte membrane in 50 ml of 0.1 M sodium hydrogen bicarbonate-1 M saline solution is added, with stirring, 400 mg of 2-acetamido-3 '- {(1-1- ( D1-Carbamoyl-3-succinimido-oxycarbonyl-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-Glucose and the mixture is stirred for 4 hours at room temperature. The erythrocyte membrane conjugate is then sedimented by hourly ultracentrifugation at 90,000 g and 4 °. The sediment is washed three times, each time by resuspension and ultracentrifugation, with phosphate buffered saline and once with distilled water. The washed erythrocyte membrane-conjugate is suspended in distilled water and lyophilized.

The determination of muramyl peptide bound to sheep erythrocytes is performed by the Morgan-Elso reaction to give 25 ug of muramyl peptide per 1 mg of sheep erythrocyte membrane.

Example 4: 100 mg of Neisseria meningitidis group C polysaccharide and 110 mg (0.2 mmol) of 2-acetamido-3-O - {(L-1- (D1-carbamoyl-3-N-aminoethylcarbamoyl) propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose-HCl is dissolved in 10 ml of distilled water, the pH of the solution is adjusted to 5 with dilute hydrochloric acid.

19.2 mg of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. HCl is added to the solution with stirring. The mixture is stirred for 1 hour at room temperature, the pH - by adding dilute sodium hydroxide - is maintained at 5, then 5 ml of 2 M sodium acetate buffer solution, pH 5, are added and stirring is continued for 30 minutes. The pH is then adjusted to 7 with sodium hydroxide solution. The solution is sterile filtered and dialyzed against distilled water at 4 ° and then freeze-dried.

Quantitative determination of desmethylmuramyl peptide coupled to C polysaccharide is performed as described in Example 1 by Morgan-Elson reaction to give 80 ug of desmethylmuramyl peptide per 1 mg of polysaccharide.

Used 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-ethyl) -methyl} -2-deoxy-D-glucose hydrochloride is prepared, for example, as follows: 1 mmol of 2-acetamino-3-o - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-Glu and 2 mmol of N-ethyl-N '- (3-dimethylaminopropyl) -carbodiimide. The HCl is dissolved in 10 ml of water and the pH is adjusted to 5 [mu] l with 666,88 parts of acid, then a solution of 5 mmol of ethylenediamine hydrochloride in 10 ml of water is added. The precipitate is stirred at pH 5, room temperature, for 6 hours. The mixture is applied to a weakly acidic cation ion exchange column - Amberlite CG 50 II, 2.5 x 45 cm and eluted with a linear gradient from 0.05 M pyridine acetate, pH 6 (300 ml) to 0.5 M pyridine acetate, pH 3.7 ( 300 ml). Prepared 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D -the fractions containing glucose acetate - the fractions are tested and identified by ninhydrin or high-voltage electrophoresis - lyophilized. The conversion to the hydrochloride form takes place as follows: the lyophilisate is dissolved in 6 ml of 0.2 N HCl and chromatographed on a Bio-Gel®P2 column (molecular sieve polyacrylamide-water).

separation range 100-1800 Daltons, manufactured by Bio-Rad), 2.5 x 90 an, as eluent / 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-N-aminoethylcarbamoyl- fractions containing propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-Glucose hydrochloride are freeze-dried. The preparation is uniform in high voltage electrophoresis. In the structure determination, the molecular ratio of 1 muramic-acid powder L-alanine: 1 D-glutamic acid: 1 ethylenediamine is observed in the total hydrolysis.

In a similar manner, the corresponding 8'-aminoethylamide.HCl compounds are prepared starting from the corresponding muramyl peptides, namely: 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-N-aminoethylcarbamoyl) -propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose.HCl, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-N-aminoethyl) (carbamoyl-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose.HCl, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-N -aminoethyl-carbamoyl-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose.HCl, 2-acetamino-3-O - {(L-1- (D1N-carbamoyl-methyl) -Carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-ethyl) -carbamoyl-methyl> -2-deoxy-D-glucose.HCl, 2-benzoylamino-3-O - {(1- 1- (Dl -Carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbimoyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose.HCl, 2-propionylamino-3-O - {(L 1- (D-3-carbamoyl-n-aminoethyl-carbamoyl-propyl) -carboxylic bamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose.HCl, 20,68787 2-acetylamino-3-O - {(1- 1- (D1-carbamoyl-3-N-aminoethylcarbamoyl) -propyl) -carbamoyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose.HCl, 2-acetylamino-3-O - {(L-1- (D1-carbamoyl-3-N-aminoethylcarbamoyl) (1-propyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose.HCl, 2-propionylamino-3-O - {(1- 1- (D1 (or 3) -carboxy) -3 (or 1) -N-amino-ethyl-carbamoyl-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose .HCl, 2-benzoylamino-3-CH (1- 1- (D1N-Carbamoyl-methyl-carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose.HCl, 2-benzoylamino-3-O - {( L-1- (D1-carboxy-3-N-aminoethylcarbamoyl-1-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose.HCl, 2-acetamino-3-O - {( L-1- (D1-Carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl i} -2-deoxy-D-glucose.HCl, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3- (1-N-aminoethylcarbamoyl) ethyl) carbamoyl-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose .HCl, 2-acetamino-3-O - {(L-1- (D1-carboxy-3-N-aminoethyl- carbamoyl-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose.HCl, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3 (N-aminoethyl-carbamoyl-propyl) -carbamoyl-N, N-tetramethylene) -carbamoylmethyl} -2-deoxy-D-glucose.HCl, 2-acetamino-3-O - {(L-1- (Dl -carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose.HCl or 2-benzoylamino-3-O - {( 1- 1- (D1-Carbamoyl-3-N-aminoethyl-carbamoyl-propyl) -carbamoyl-21-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose .HCl.

These compounds are condensed as described above with a group C polysaccharide from Neisseria meningitidis.

Example 5: Immediately after isolation, the total yield of the malaria-causing Plasmodium knowlesi Merozoite from the blood of an infected rhesus monkey (method for preparing merozoites: see G.H. Mitchel et al.

21 66878 (1975), Immunology, 29, 397) is suspended in a solution of 100 mg (0.17 mmol) of 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-succinimido- oxycarbonyl-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose in 15 ml of physiological saline solution pH 7.2. The suspension is incubated for one hour at 37 °. The conjugate is then precipitated by centrifugation. The pellet is washed by resuspension in physiological buffer and recentrifuged. The washed merozoite conjugates are suspended in G.H. According to Mitchell (see reference above) in 10% autologous rhesus monkey serum and lyophilized.

Quantitative determination of muramyl peptide bound to merozylites is performed by the Morgan-Elso reaction to give 40-60 ug of muramyl peptide per 1 mg of merozylite.

Example 6:

To a solution of 200 mg (0.34 mmol) of 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-succinimidooxycarbonyl-propyl) -carbamoyl-ethyl) -carbamoyl -methyl} -2-deoxy-D-glucose in 20 ml of phosphate buffered saline, pH 7.2, o 10 T early lymphocytes from CBA / J mice are suspended. (Early lymphocyte cells were prepared in mixed lymphocyte culture against C57BL / 6 mouse stimulator cells, LC.Anderson et al., (1977), The Journal of Experimental Medicine, 146, 1124). The suspension is incubated for 90 minutes at room temperature. The early lymphocyte conjugates are then precipitated by centrifugation and washed by resuspension in phosphate-buffered saline and recentrifuged.

Quantitative determination of muramyl peptide associated with early T cells is performed by the Morgan-Elso reaction (see Example 1) to give 6-70 ug of muramyl peptide per 10 T early cells. Example 7;

In a manner similar to the above examples, bovine serum albumin is obtained in association with the following compounds: 2-acetamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} - 2-Deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2- deoxy-α, 3-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy- α, 3-D-glucose, 2-acetamido-3-O - {(L-1- (D1-carbamoylmethylcarbamoyl-3-carboxypropyl) carbamoylethyl) carbamoylmethyl} -2-deoxy-D-glucose si, 22 66878 2-Benzamido-2-deoxy-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoylmethyl} -D-glucopyranose, 3-O- ((1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-2-propionamido-D-glucose and 2-acetamido-3-o - {(L-1- (Dl carbamoyl-3-carboxypropyl) -karbamoyy-lip propylamide) -karbamoyyliraetyyli} -2-deoxy-D-glucose.

2-Acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3- O - {(1- 1- (D1,3-dicarboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzylamino-3-O - {(1- 1- (D1N-carbamoylmethyl) -Carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose> 2-acetamino-3-O - {(D1- (L1-carbamoyl-3-carboxy-propyl) - Carbamoyl-2'-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1,3-dicarboxy-propyl) -carbamoylethyl) - carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-2'-methylpropyl) carbamoylmethyl } -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3- (L-1-carboxyethyl) carbamoylpropyl) carbamoylethyl) -Carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1,3-dicarboxypropyl)? carbamoyl-2 ' -methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N-N , N-Tetramethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) ) -N-methylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-21-methyl) propyl) -carbamoyl-methyl} -2-deoxy-D-glucose.

Example 8:

In a manner similar to Example 3, sheep erythrocyte membranes are obtained in association with the compounds: 2-acetamino-3-O- {D1- [1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- [1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D -glucose, 2-benzoylamino-3-O - {[L-1- (D1-carbamoyl-3-carboxypropyl) -2,266,878 carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino -3-O - {(1- 1- (D, 1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(1-1 - (D1-carbamoyl-3-carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1N-carbamoylmethylcarbamoyl-3-carboxy) (s-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-propyl) - karbamoyylimety over} -2-deoxy-D-glucose, 2-acetylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy- D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- propionylamino-3-O - {(1- (1- (1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-1-glucose-2-benzoylamino-3-O - {(1 -1- (D1N-carbamoylmethyl-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (Dl- carbamoyl-3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1 -Carbamoyl-3- (L-1-carboxyethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (Dl, 3 (dicarboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- ( D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-tetramethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- ( D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3 carboxy-propyl) -karbamoyy-yl-2'-methyl-propyl) -Carbamoylethyl} -2-deoxy-D-glucose. Example 9;

In a manner similar to Example 5, merozoites of the malaria-causing Plasmodium knowlesi are obtained in association with the compounds: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamyl). Ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl -ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy- D-glucose, 2-benzoylamino-3-O - {(L1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose-2-propionylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (DlN- carbamoylmethylcarbamoyl-3-carboxypropyl) carbamoylethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl (1-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetylamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoylpropyl) -carbamoyl-methyl} - 2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(1- 1- (D, 1,3-dicarboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose-2-benzoylamino-3-O - {(1 -1- (D1N-carbamoylmethyl-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (Dl-carbamoyl- 3-carboxy-propyl) -carbamoyl-1,2-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-) 3- (L-1-carboxyethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1,3-dicarboxypropyl) -Carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benz Zoylamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3 -O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N-N, N-tetramethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- { D1- (L1-Carbamoyl-3-carboxy-propyl) -carbamoyl-21-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose.

25 66878

Example 10:

To a solution of 100 mg of 2-acetamino-3-O- {D-1- (1- 1- (D1-carbamoyl-3-succinimidooxycarbonyl-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl } -2-deoxy-D-glucose in 10 ml of phosphate buffered saline, pH 7.2, is suspended in 10 canine mammary cancer cells (Tumor cells were prepared according to the method of HHSedlacek, H. Messmann and FRSeiler, Behring Inst. Mitt ., No. 55, 349-355 (1974)). The suspension is incubated for 90 minutes at room temperature. The tumor cell-muramyl peptide conjugates are then precipitated by centrifugation and washed by resuspension in phosphate-buffered saline and recentrifuged.

Quantitation of muramyl peptide associated with tumor cells is performed by the Morgan-Elso reaction (see Example 1) and yields 60-80 μg muramyl peptide per 10 mammalian cancer cells.

Example 11:

In a manner similar to Example 10, canine mammalian cancer cells are obtained in association with the compounds: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy -D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino -3-O - {(L-1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(1-1 - (D1-carbamoyl-3-carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1N-carbamoylmethylcarbamoyl-3-carboxy) (s-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) - carbamoylmethyl} -2-deoxy-D-glukoo si, 2-acetylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino- 3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 26 66878 2-propionylamino-3-O- {(1- 1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1N-carbamoylmethyl) -Carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) ) -carbamoyl-1'-2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-1-glucose, 2-acetamino-3-O- {D1- (L-1- (D-1-carbamoyl-d- ( L-1-carboxy-ethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1,3-dicarboxypropyl) ) -carbamoyl-2'-methylpropyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl) 1- (3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl) -3-carboxy-propyl) -carbamoyl-Ιΐ-Ν, Ν-tetramethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (Dl-carbamoyl) -3-carboxy-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3-carboxy- propyl) -karbamoyy-yl-2'-methyl-propyl) -Carbamoylethyl} -2-deoxy-D-glucose. Example 12: To 10 ml of a vaccine suspension of foot-and-mouth disease culture in Beringwerke's phosphate-buffered saline, 100 mg of 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-succinimidooxycarbonyl) is added. propyl) -carbamoyl-ethyl) -carbamic-methyl-sulfamoyl} -2-deoxy-D-glucose. The suspension is shaken for 4 hours at 4 °. The viral muramyl peptide conjugate is then sterile filtered, dialyzed against low molecular weight reaction products, and lyophilized. Quantitative determination of muramyl peptide associated with viruses is performed by the Morgan-Elso reaction (see Example 1).

Example 13:

In a manner similar to Example 12, a foot-and-mouth disease vaccine is obtained in association with the compounds: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl- Ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2 -deoxy-D-glucose, 27 66878 2-Benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose , 2-Benzoylamino-3-O - {(1- 1- (D, 1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O- {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1N-carbamoylmethylcarbamoyl) -3-Carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose-2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) carbamoyl-propyl)} Carbamoylmethyl - 2-deoxy-D-glucose, 2-acetylimino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy-D- glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino- 3-O - {(1- 1- {D1,3-decarboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1-1- ( D1N-carbamoylmethyl-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (Dl-carbamoyl-3- carboxy-propyl) -carbamoyl-1H-21-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3- (L1-Carboxyethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-dicarboxypropyl) -carbamoyl -21-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose-2-benzoylamino-3-O - {(L-1- (Dl -Carbamoyl-3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (Dl- carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-tetramethylene) -carbamoyl-methyl} -2-deoxide-D-glucose-2-acetamino-3-O - {(L-1- (Dl -carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3- carboxy-propyl) -carbamoyl-1'-2'-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose.

28 66878

Example 14:

In a manner similar to Example 6, TBA early T conditions were obtained in CBA / J mice coupled to: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl -ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} - 2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-Benzoylamino-3-O - {(L-1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {( L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (DlN-carbamoylmethylcarbamoyl-3 (carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl- propyl) -2-Carbamoylmethyl} Deso xy-D-glucose, 2-acetylamino-3-O - {(1-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-Acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-1,2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3- O - {(L-1- (D1,3-dicarboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose / 2-benzoylamino-3-O - {(L-1- (D1N-carbamoylmethyl) -Carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-N-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) ) -carbamoyl-1H-2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3- (L1) (carboxy-ethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-dicarboxypropyl) -carbamoyl -2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl) yl-3-carboxy-propyl) -carbamoyl-21-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-) 3-carboxy-propyl) -carbamoyl-1-N, N-tetramethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 29,66887 2-acetamino-3-O - {(1- 1- (D1- carbamoyl-3-carboxy-propyl) -carbamoyl-1-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3 -carboxy-propyl) -carbamoyl-1H-2'-methyl-nropyl) -carbamoylethyl} -2-deoxy-D-glucose, Example 15; 1 mg Naida serum albumin-2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose- the conjugate is dissolved in 0.1 ml of phosphate-buffered saline (PBS); 0.1 ml of a 5% suspension of carboxymethylcellulose in PBS is mixed with the solution.

This mixture is administered in two equal doses intramuscularly to a hamster.

Example 16: - 10 T-early mucin-2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D -glucose conjugate (see Example 6) is suspended in 0.5 ml of phosphate buffered saline (PBS); the suspension is mixed with 0.5 ml of a 5% suspension of carboxymethylcellulose in PBS. This mixture is administered subcutaneously at 0.1 ml per mouse.

Example 17: To 10 ml of a rabies HDC vaccine suspension in Behringwerke phosphate-buffered saline, 100 mg (0.17 mmol) of 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-succin) are added. (imido-oxycarbonyl-propyl) -carbamoyl-ethyl) -carbamoyl-7-methyl} -2-deoxy-D-glucose. The virus concentration is 2 x 10 ld ^ q / mouse in 1 ml of suspension. The suspension is shaken for 4 hours at 4 °. The muramyl peptide-water horror-HDC vaccine conjugate is then sterile filtered, dialyzed against low molecular weight reaction products, and lyophilized.

Example 18:

In a manner similar to Example 17, the rabies HDC vaccine Behringwerke coupled with the compounds: 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl- Ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2 -deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 30 66878 2-Benzoylamino-3-O - ((1- 1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O- { (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1N-carbamoylmethylcarbamoyl-) 3-Carboxy (propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-N-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) propyl) -karbamoyylimetyy 1H} -2-deoxy-D-glucose, 2-acetylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoylpropyl) carbamoylmethyl} -2-deoxy D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-1-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- propionylamino-3-O - {(1- 1- (D1,3-dicarboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- (D1N-carbamoylmethyl-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (Dl-carbamoyl-3 -carboxy-propyl) -carbamoyl-1'-2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-) 3- (L-1-carboxyethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-dicarboxy- propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (Dl -Carbamoyl-3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (Dl- carbamoyl-3-carboxypropyl) carbamoyl-N, N-tetramethylene) carbamoylmethyl} -2-deoxy-D-glucose / 2-acetamino-3-O - {(1- 1- (D1-carbamoyl) -3-carboxy-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3-carboxy- propyl) -carbamoyl-2'-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose. Example 19: To 10 ml of a suspension of extracted influenza virus antigen Typ A / Victoria) 3/75 in phosphate buffered saline is added 100 mg (0.17 mmol) of 2-acetamino-3-O - (( l-1- (D-carbamoyl-3-succinimido-carbonyl-oxy-propyl) carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose.

31 66878 (Viral antigen was prepared according to the Tween / ether cleavage method, Behringwerke, Marburg, BRD - corresponding to the preparation of Begrivac S? Concentration is 4000 I.E. in 1 ml of suspension). The suspension is shaken for 4 hours at 4 °. The virus-antigen-muramyl peptide conjugates are then separated by dialysis against phosphate-buffered saline from small molecule reaction products; the dialyzed suspension is frozen and stored at -20 ° until used.

Example 20;

In an analogous manner to Example 19, an influenza virus antigen is obtained in association with the compounds: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl -ethyl) -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl) -2- deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- benzoylamino-3-O - {(L-1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(L- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1N-carbamoylmethylcarbamoyl-3-carboxylate) (s-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-propyl) Carbamoylmethyl} -2-deoxy-D-glu cose, 2-acetylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino- 3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbaraoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {( L-1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1N-carbamoylmethyl-carbamoyl) -3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) - carbamoyl-21-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- (D1- (L-1- (D1-carbamoyl-3- (L1-carboxy) ethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 32 66878 2-acetamino-3-O - {(1- 1- (D1,3-dicarboxypropyl) -carbamoyl- 2'-Methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-gluco-1,2-benzoylamino-3-O - {(1- 1- (D1-carboxyl) Amoyl-3-carboxy-propyl) -carbamoyl-21-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-) 3-Carboxy-propyl) -carbamoyl-1-N, N-tetramethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetazino-3-O - {(1- 1- (D1-carbamoyl-) 3-carboxy-propyl) -carbamoyl-1-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3-carboxy) -propyl) -carbamoyl-2'-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose. Example 21: To 2 ml of a solution of tetanus toxoid in phosphate-buffered saline is added 10 mg of 2-acetamido-3-O - {(1- (1-carbamoyl-3-succinimidooxycarbanyl). propyl-phenyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose. The toxoid concentration is 3 mg / ml. The solution is stirred for 4 hours at 4 °. The tetanus toxoid-muramyl peptide conjugate is then separated from the low molecular weight reaction products by ultrafiltration; the ultrafiltered solution is frozen and stored at -20 ° until use. The quantitative assay (Morgan-Elson reaction) gives about 50 pg of muramyl peptide per 1 mg of tetanus toxoid-muramyl peptide conjugate.

Example 22:

In a similar manner to Example 21, tetanus toxoid is coupled to the following compounds: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2- deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D- glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3- O - {(1- 1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(1-1 (Dl -Carbamoyl-3-carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1N-carbamoylmethylcarbamoyl-3-carboxy-propyl) ) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 33 66878 2-Benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoylmethyl } -2-deoxy-D-gl ucose, 2-acetylamino-3-O - {(1-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino- 3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {( 1- 1- (D1,3-Dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1N-carbamoylmethyl-carbamoyl) -3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl- 1H-2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3- (L-1-carboxy) -ethyl) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1,3-dicarbaboxypropyl) -carbamoyl-2 '-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carbo) (xi-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-N-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-N, N-tetramethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-ethyl) -N-methylcarbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3-carboxy-propyl) -carbamoyl- 2'-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose. Example 23: To 10 ml of a solution of cholera toxoid from Vibrio cholerae in phosphate buffered saline is added 50 mg of 2-acetamido-2-O - {(L1- (D1-carbamoyl-3-succinimidooxycarbonylpropyl). ) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose. The protein concentration in the solution is 0.6 mg / ml. The solution is stirred for 4 hours at 4 °. The cholera toxoid-muramyl peptide conjugate is then separated by ultrafiltration from the small molecule reaction products? the ultrafiltered solution is frozen and stored at -20 ° until use. Quantitative assay (Morgan-Elson reaction) gives 40-50 μg muramyl peptide per 1 mg cholera toxoid-muramyl peptide conjugate.

34 66878

Example 24:

In a similar manner to Example 23, tetanus toxoid is coupled to the following compounds: 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl } -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2- deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- benzoylamino-3-O - {(1- 1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(1- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1N-carbamoylmethylcarbamoyl-3-carboxylate) (s-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-propyl) Carbamoylmethyl} -2-deoxy-D-glucose , 2-acetylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O - {(L-1 - (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1N-carbamoylmethyl-carbamoyl-3- carboxy-propyl) -carbamoyl-ethyl) -carbimoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D-1- (L-1 (D1-carbamoyl-3- (L1-carboxy-ethyl) ) -carbamoyl-propyl) -carbamoylethyl) -carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-dicarboxypropyl) -carbamoyl-2'- methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carbamyl) Boxoxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) ) -carbamoyl-1-N, N-tetramethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 66878 35 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy) (propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3-carboxy-propyl) -carbamoyl -li-2'-methyl-propyl) -karbeunoyylietyyli} -2-deoxy-D-glucose. Example 25: 20 mg of a synthetic eicosapeptide identical to the C-terminal sequence of human chorionic gonadotropin (HCD) (Reference: CHSchneider, K.Blaser, Ch.Pfeuti and E.Gruden, Febs. Letters, 50, 272 (1975)) and 30 mg of 2-acetamido-3-O - {(L1- (D1-carbamoyl-3-succinimidooxycarbanyl-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D -glucose is dissolved in 2 ml of sodium phosphate buffer solution, pH 7.2. The solution is stirred for 6 hours at room temperature. The eicosapeptide-muramyl peptide conjugate is then chromatographed on a Sephadex G-25 column (1.4 x 40 cm) eluting with water and freeze-dried. Quantitative amino acid analysis shows that the 1-muramyl peptide molecule is bound to the 1-eicosapeptide molecule.

Example 26:

In a manner similar to Example 25, a C-terminal eicosapeptide fragment of human chorionic gonadotropin coupled to the following compounds is obtained: 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose , 2-benzoylamino-3-O - {(L-1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-propionylamino-3-O- { (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1N-carbamoylmethylcarbamoyl-) 3-Carboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) - propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetylamino-3-O - {(L-1- (D1-carbimimoyl-3-carboxy-propyl) -carbamoylpropyl) -carbamoylmethyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-36,6878 1H-2-hydroxyethyl) -carbamoylmethyl} -2-deoxy-D- glucose, 2-propionylamino-3-O - {(1- 1- (D1,3-dicarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {(1- 1- (D1N-carbamoylmethyl-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1 - (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2'-methyl-propyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3- (L-1-carboxyethyl) carbamoylpropyl) carbamoylethyl) carbamoylethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1,3-Dicarboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D -glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D- glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-tetramethylene) -carbamoyl-methyl} -2-deoxy-D- glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1-carbamoyl-3-carboxy-propyl) -carbamoyl-21-methyl-propyl) -carbamoylethyl} -2-deoxy-D-glucose. Example 27:

In a manner similar to Example 1, bovine serum albumin is coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} -2-deoxy- D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} -2-deoxy-D-glucose, 2- acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino- 3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3- O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamido-3-O- {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {( 1- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl-k arbamoylmethyl} -2-deoxy-D-glucose, 37 66878 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-N, N-pentamethylene ) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) - carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -N-methyl-carbamoyl-ethyl) - carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoyl ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl-carbamoyl-ethyl} -2-deoxy -D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-ethyl} -2 -deoxy-D-glucose-2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-ethyl} - 2-deoxy -D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2 -deoxy-D-glucose, 2-benzamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-ethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -carbamoyl- ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbimoyl-3-carboxy; i-propyl) -carbamoyl-N / N-pentamethylene) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl-carbamoyl-ethyl) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy- D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-car bamoyl-3-carboxymethyl-phenyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) ) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxid-D-glucose, 2-benzamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) ) -carbamoyl-2-chloroethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3,3-dicarboxy) -propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 38 66878 2- (8-carbomethoxy-succinamido) -3-O - {(1- 1- (D1-carbamoyl-3-carboxylate) (s-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (8-carbomethoxy-succinamido) -3-O- {D1- (1- 1- (D1-carbamoyl) -3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1- 1- (D1-carbamoyl-3-trimethylsilyl-carboxy) -propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-trimethylsilyl-D-glucose (in contact with water trimethylsilyl) sterile group is saponified rapidly), 2-acetamino-2-deoxy-3-O - {(1- 1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} -1,4,6 -tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) -carbamoyl-ethyl } -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p-hydroxy- phenyl) -ethyl) -carbamoyl-ethyl} -2-desoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carb -bamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl)) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) - carbamoyl-methyl 1} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-ethyl) -carbamoyl- methyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-ethyl) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p- hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1- (L1-carboxyethyl) carbamoyl-3-benzyl) silylcarboxy-propyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 39 66878 2-acetamino-3-O - {(L1- (D1,3-dicarboxypropyl) -N-methylcarbamoyl -ethyl) -carbamoylmethyl} -2-deoxy-D-glucose Example 28;

In a manner similar to Example 3, sheep erythrocyte membranes are coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} -2 -deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose , 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose , 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose , 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose , 2-Benzamido-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose , 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) ) -N-propylcarbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-N , N-pentamethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N -pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -N-methyl-carbamoyl) -ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D-carbamoyl-3-carboxy-propyl) -carbimimoyl-methyl) -N-methyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl- Ethyl} -2-deoxy-D-glucose-2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl carbamoyl-ethyl} -2-des oxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carbarboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} - 2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoylpropyl) -N-ethylcarbimoyl-ethyl} - 2-deoxy-D-glucose, 40 66878 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl-carbamoyl -ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -N-roethyl-carbamoyl-ethyl) -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy -D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - ((L-1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-chloroethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L- 1- (D1-Carbamoyl-3,3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2- (3-carbomethoxy-succinamido) -3-O - ((1- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (g-carbomethoxy-succinamido) -3-O- {Dl - (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L-1- (D-Carbamoyl-3-trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (in contact with water, trimethyl the isyl ester group is rapidly saponified), 2-acetamino-2-deoxy-3-O - {(1- 1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} -1,4 , 6-Tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) -carbamoyl-ethyl } -2-deoxy-D-glucose, 2-acetcunino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbam) 41 66878 bamoyl-2 '- (p- hydroxy-phenyl) -ethyl) -carbamoyl-ethyl} -2-desoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl)) -Carbamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy) propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl i) -Carbamoylmethyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) - carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) ) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carboxylate) bamoyl-2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1- (L1-carboxyethyl) carbamoyl) -3-Benzylcarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-dicarboxy-propyl) ) -N-methyl-carba-sulfamoyl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 29;

In a manner similar to Example 4, a group C polysaccharide of Neisseria meningitidis is coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoylmethyl } -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoylmethyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy- D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy- D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy- D-glucose, 2-benzamido-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy- D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) carbamate yl-ethyl) -N-propyl-carbamoyl-methyl} -2-deoxy-D-glucose, 42 66878 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carboxylate) moyl-N, N-pentamethylene) -carbamoylmethyl) -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl- N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxypropyl) -N-methyl- carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl-carbamoyl-ethyl } -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxypropyl) -carbaraoyl-ethyl) -N-ethyl-carbamoyl-ethyl } -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl- carbamoylmethyl} -2-deoxy-D-glucose, 2-bentamido-3-O- {D1- (L1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) -N-ethyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L1- (D1-carbaraoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -carbamoyl- Ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -N-methylcarbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-methyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- benzoyl Amino-3-O - {(L1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L1- ( (1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1-1 - (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1-1 - (D1-Carbamoyl-3,3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 43 66878 2- (β-carbomethoxy-succinamido) -3-O- ((1 -1- (D1-Carbamoyl-3-carboxy-1-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1-glucose, 2- (β-carbomethoxy-succinamide) -3-O- ( D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1-1 - (D1-Carbamoyl-3-trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (contact trimethylsilyl ester group is rapidly saponified with water), 2-acetamino-2-deoxy-3-O - {(L-1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} - 1,4,6-Tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- (D-1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -propyl ) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy -propyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- (D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 (p-hydroxy-phenyl) -ethyl) -carbimoyl-ethyl} -2-desoxy-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy) -propyl) -carbamoyl-N, N-tetramethylene) -carbamoyl-ethyl) -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {[L-1- (D1-carbamoyl-3-carb Boxoxypropyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O - ((L-1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- (Dl- (L-1- (Dl- carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- (D1- (L-1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy) -propyl) -carbamoyl-2 '- (p-hydroxyphenyl) -ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - ((L-1- (Dl- (L1-Carboxy-ethyl) -carbamoyl-3-benzylcarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 44 66878 2-acetamino-3-O - {(1- 1- (dI, di-3-carboxy-propyl) -N-methyl-carba-sulfamoyl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 30:

In a manner similar to Example 5, merozoites of the malaria-causing Plasmodium knowlesi are coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl } -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2- deoxy-D-glucose, 2-benzamido-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) - carbamoyl-ethyl) -N-propyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl)) -Carbamoyl-N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) - carbamoyl-N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -N- methyl-1'-carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-N-glucose-2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl- methyl) -N-methylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N -methyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) i) -N-methyl 1-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) - N-ethylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoylpropyl) -N-ethylcarbamoyl-ethyl} -2-deoxy-D-glucose, 45 66878 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl- ethyl) -N-propylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carboxylate). bamoyl-N, N-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) - carbamoyl-Ιΐ, Ν-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) ) -N-methylcarbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxymethyl-phenyl) ) -carbamoyl-methyl} -2-deoxy-D-glucose , 2-Benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O- {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- { D1- (L-1- (D1-carbamoyl-3,3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamino) -3 -O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O- { (1- 1- (D1-carbamoyl-3-trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (contact the trimethylsilyl ester group is rapidly saponified with water), 2-acetamino-2-deoxy-3-O - {(L-1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} - 1,4,6-Tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl- Ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p -hydroxy-phenyl) -ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 46 66878 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) ) -carbamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy) -propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxylate) Si-propyl) -carbamoyl-ethyl) -carbamoyl-methyl) -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O - ((1- 1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- (Dl- (1- 1- (Dl- carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose / 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-21-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-21- (p-hydroxyphenyl) -ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (Dl- (L -1-carboxy-ethyl) -carbamoyl-3-benzylcarboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- ( D, 3-dicarboxy-propyl) -N-methyl-carbamoyl-yl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 31:

In a manner similar to Example 6, early T cells of CBA / K mice are obtained coupled to the following compounds: 2-acetamino-3-O - (((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoyl- methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-benzamido-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-pr opylcarbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-N, Ν-pentamethylene ) -carbamoylmethyl} -2-deoxy-D-glucose, 66878 2-benzoylamino-3-O - [(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-N, N- pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -N-methyl-carbamoyl- ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- [1-(- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbaraoylmethyl) -N-methyl-carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N- karbeunoyyli-methyl-ethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl- ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N- pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N -pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl) -Carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl) } -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1 - (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose / 2-benzamino-3-O - {(L-1- (Dl-carbamoyl-3-carboxy) -propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L-1- (D1-carbamoyl-3 -carboxy-propyl) -carbamoyl-2-chloroethyl) -carbimimoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbimimoyl-3) (3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose / 2- (β-carbomethoxy-succinamido) 3-O - {(L-1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 48 66878 2- (β-carbomethoxy-succinamido) -3-O- {D1- (1- 1- (D1- carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1- 1- (D1-carbamoyl-3-trimethylsilyl) carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (in contact with water tr the imethylsilyl ester group is saponified rapidly), 2-acetamino-2-deoxy-3-O - {(L-1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -1,4 , 6-Tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetyl-3-O- {D1- (L-1- (D1-carbamoyl-3-: carboxypropyl) -carbamoyl-21-hydroxypropyl) -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- ( p-hydroxy-phenyl) -ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl)) -carbamoyl-N, Ν-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {Dl- (1- 1- (Dl-carbimoyl-3-carboxy) propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl i-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) ) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy) (propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl)) -carbamoyl-2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {{L-1- (D1-carbamoyl-3-carboxy-propyl) - carbamoyl-2 '- (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1- (L1-carboxyethyl) ) -carbamoyl-3-benzylcarboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-di- carboxy-propyl) -N-methyl-carba-sulfamoyl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

49

Example 32: 6 6 8 7 8

In a manner similar to Example 12, a Behringwerke foot-and-mouth disease culture vaccine coupled with the following compounds is obtained: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N- methylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl} -N-ethyl-carbamoyl- methyl> -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl- methyl} -2-deoxy-D-glucose, 2-benzamido-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-p- propyl) -carbamoyl-ethyl) -N-propyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy) propyl) -carbamoyl-N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl)) -N-methyl-carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl ) -N-methylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N- methyl i-carbimoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -ethyl) -N-ethylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) carbo) -bamoyyli-propyl) -nm ethylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) - N-ethylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoylpropyl) ) -N-ethylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -ethyl) -N-propylcarbamoyl-ethyl} -2-deoxy-D-glucose, 50 66878 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl)) -Carbamoyl-N, N-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-N, N-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3- carboxy-propyl) -N-methyl-carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy- methylphenyl) -carbamoyl-methyl} -2-deoxy-D-glukoo si, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3 -O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino -3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3 -O- {D1- (L-1- (D1-carbamoyl-3,3-dicarboxypropyl) carbamoylethyl) carbamoylethyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamino) —3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy- succinamino) -3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbimoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3 -0 - {(l-1- (D-karbcunoyyli-trimethylsilyl-3-carboxy-propyl) carbamoyl-ethyl) -carbamoyl-methyl} -2-desoxy-l, 4,6-tris-trimethylsilyl-D-glucose (kos preferably with water, the dimethylsilyl ester group is rapidly saponified), 2-acetamino-2-deoxy-3-O - {(L-1- (D1-carbamoyl-3-trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} - 1,4,6-Tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl -ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) ) -carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p-hydroxy-phenyl) -ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 51 66878 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3) -carboxy-propyl) -carbamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbaoyl) -3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(b1- (D1-carbamoyl-3-carboxylate) Si-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O - {(1- 1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O- {D1- (1- 1- (D1- carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-21-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-21- (p-hydroxyphenyl) -ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1- (L -1-carboxy-ethyl) -carbamoyl-3-benzylcarboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- ( D, 3-di-carboxy-propyl) -N-methyl-carba-sulfamoyl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 33:

In a manner similar to Example 17, the rabies HDC vaccine Behringwerke is coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} - 2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoylmethyl} -2-deoxy- D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D- glucose, 2-acetamino-3-O - {(1- 1- (D1-carbimimoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D- glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D- glucose, 2-benzamido-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D- glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carba -Noyl-ethyl) -N-propyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carba -moyl-N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 52 66878 2-Benzoylamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -N-methyl -1-carbaraoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) - N-methylcarbainoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methyl -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl -carbamoyl-ethyl) -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl i-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N- Ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N- propylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamimoyl-3-carboxy-propyl) -carbamoyl-N, N -pentamethylene) -carbamoyl-ethyl) -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-N, N -pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl) -Carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} - 2-deoxy-D-glucose, 2-Bent soylamino-3-O - {(L1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L1- ( D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L1- ( Dl-carbamoyl-3-carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {Dl- (Ll- (Dl- carbamoyl-3,3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O - ((L1- (D1-carbamoyl- 3-Carboxy-53,6878 (propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O- {D1- (L1- ( D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L1- (D1-carbamoyl-3- Trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (contact in water, the trimethylsilyl ester group is saponified rapidly), 2-acetamino-2-deoxy-3-O - {(L1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -1, 4,6-Tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl } -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) -carbamoyl- Ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p-hydroxy -phenyl) -ethyl) -carbamoyl-ethyl} -2-desoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carb -bamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- (D1- (L1- (D1-carbamoyl-3-carboxypropyl)) -Carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-p- propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O - {(1- 1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- {D1- (1- 1- (D1-carbamoyl-) 3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1-carbimoyl-3-carboxy-propyl) - carbamoyl-2 '- (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1- (L1-carboxy) -ethyl) -carbamoyl-3-benzylcarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1, 3- dicarboxy-propyl) -N-methyl-carba- (54,6878moyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose,

Example 34t

In an analogous manner to Example 19, the influenza virus antigen Typ A / Victoria / 3/75 is obtained coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N- methylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1-1- (D1-carbamoyl-3-carboxypropyl) carbamoylpropyl) -N-ethylcarbamoyl- methyl} -2-deoxy-D-glucose, 2-benzamido-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl- methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) (li) -carbamoyl-ethyl) -N-propyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy) propyl) -carbamoyl-N, Ν-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl)) -N-methyl-1-carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carba -moyl-methyl) -N-methyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- (D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) ) -N-methylcarbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbose) -bamoyl-ethyl) -N-ethyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl)) -carboxylic carbamoyl-propyl) -N-methyl-carboxylic bamoyl-ethyl} -2-deoxy-D-glucose / 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N- Ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) - N-ethylcarbamoyl-ethyl} -2-deoxy-D-glucose, 55 66878 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) ) -N-propylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -N, N-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- 1- (D1-carbaraoyl-3-carboxy-propyl) -carbamoyl) -N, N-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl)) -N-methyl-carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxymethyl) phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-be N -oylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-bentamino-3-O- { (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O- { (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {Dl- (1- 1- (D1-carbamoyl-3,3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O- (1- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O - (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1 -1- (D1-Carbamoyl-3-trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (in contact with water with n, the trimethylsilyl ester group is saponified rapidly), 2-acetamino-2-deoxy-3-O - ((1- 1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} -1,4,6-Tris-trimethylsilyl-D-glucose, 2-azetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) - carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy- propyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carboxylic acid) 2 '- (p-hydroxy-phenyl) -ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) (i) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O - {(L1- (D1-carbamoyl-3-carboxypropyl) (li) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- (D1- [L1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 ' - (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1- (L1-carboxyethyl) carbamoyl) 3-Benzylcarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L1- (D1,3-dicarboxy-propyl) -N -methyl-carba-sulfamoyl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 35;

In a similar manner to Example 21, tetanus toxoid is coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methylcarbamoylmethyl} -2 -deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbeunoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose , 2-acetamino-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino -3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3 -O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamido-3-O - {(L1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- { (LL (D-carbamoyl-3-carboxy-propyl) -carbamic-sulfamoyl-ethyl) -N-pr opylcarbamoylmethyl} -2-deoxy-D-glucose, 57 66878 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-N, N -pentamethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {[L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N -pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl-carbamoyl) -ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoylmethyl) -N-methyl-carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -N-ethyl- carbamoyl-ethyl> -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N- methyl-carbamoyl-ethyl} - 2-Deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl } -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl -ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl -Carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N- pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1- (1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N- pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl-carbamoyl- Ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2 -deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (Dl -Carbamoyl-3-carboxymethyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy- propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbimimoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1- 1- (D1-carbamoyl-3- carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3, 3-Dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 66878 58 2- (8-carbomethoxy-succinamido) -3-O - {(1- 1- (Dl-carbamoyl-) 3-Carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamino) -3-O- {D1- (1- 1- ( D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1- 1- (D1-carbamoyl-3- trimethylsilylcarboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (in contact with water the ylsilyl ester group is saponified rapidly), 2-acetamino-2-deoxy-3-O - {(1- 1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} -1,4,6 -tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) -carbamoyl-ethyl } -2-deoxy-D-Glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p- hydroxy-phenyl) -ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carb -bamoyl-N, N-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl)) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) - karbamo ylmethyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) carbamoyl ethyl) ) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2' - (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1- (L1-carboxyethyl) carbamoyl) 3-Benzyl-1-carboxy-propyl (1-carbamoyl-ethyl) -carbamoyl-1-methyl-2-deoxy-D-glucose, 59 66878 2-acetamino-3-O - {(1- 1- (dI, di-3-carboxy-propyl) -N-methyl-carbamoyl-yl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 36:

In a manner similar to Example 23, cholera toxoid of Vibrio cholerae is coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoylmethyl} -2-deoxy -D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy -D-glucose, 2-benzamido-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D -glucose, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl) -ethyl) -N-propylcarbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl) -N, N-pentamethylene) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-N , Ν-pentamethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-1-methyl) - N-methylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- {D1 - ((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methyl- carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N- ethylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) - n-methyl-carbamoyl-ethyl} - 2-Deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl } -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl -ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl -Carbamoyl-ethyl} -2-deoxy-N-glucose, 60 66878 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N Pentamethylene-carbamoyl-ethyl} -2-deoxy-D'-glucose, 2-benzoylamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-N, N -pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl) -Tyl-carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoyl -methyl} -2-deoxy-D-glucose, 2-benzoylamino-3- O - {(1- 1- (D1-carbamoyl-3-carboxymethyl-phenyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1-1 - (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-methyl-mercapto-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L -1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2-chloroethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {Dl- (1 -1- (D1-carbamoyl-3,3-dicarboxy-propyl) -carbamoylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O - ((1 -1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- (β-carbomethoxy-succinamido) -3-O- (Dl- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - ((1-1- ( D1-carbamoyl-3-trimethylsilylcarboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (in contact with water trimethylated the ylsilyl ester group is saponified rapidly), 2-acetamino-2-deoxy-3-O - {(1- 1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) -carbabamoyl-ethyl) -carbamoylmethyl} -1,4,6 -tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl} -2 -deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) -carbamoyl-ethyl } -2-deoxy-D-glucose 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2 '- (p-hydroxy-phenyl) ) -ethyl) -carbamoyl-ethyl} -2-desoxy-D-glucose, 2-acetamino-3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carboxylate) bamoyl-N, N-tetramethylene) -carbabamoyl-ethyl} -2-deoxy-D-glucose, 61 66878 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) ) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-glycolylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl- ethyl li) -Carbamoylmethyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O - {(L-1- (Dl-carbamoyl-3-carboxypropyl) - carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2- (N-methylacetamino) -3-O- {D1- (L-1- (D1-carbamoyl-3-carboxypropyl) ) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- (D1- (L-1- (D1-carbamoyl-3-carboxypropyl) -carboxylate) bamoyl-21-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl- 2 '- (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1- (L-1-carboxyethyl) ) -carbamoyl-3-benzylcarboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-di- carboxy-propyl) -N-methyl-carba-sulfamoyl-ethyl) Carbamoylmethyl} -2-deoxy-D-glucose.

Example 37:

In a manner similar to Example 25, a synthetic eicosapeptide identical to the C-terminal sequence of human chorionic gonadotropin is coupled to the following compounds: 2-acetamino-3-O - {((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoylmethyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - {((D1-carbamoyl-3-carboxypropyl) carbamoylmethyl) -N-methyl -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl -methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl -methyl} -2-deoxy-D-glucose, 2-acetamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl -methyl} -2-deoxy-D-glucose, 2-benzamido-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl methyl} -2-deoxy-D-glukoo si, 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamido-3-0 - {(l-1- (D-carbamoyl-3-carboxy-propyl) -carbamic-sulfamoyl-n, n-pentamethylene) -carbamoyl-methyl} -2-deoxy-D-glucose; 2-Benzoylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -carbamoyl-methyl} -2-deoxy-D-glucose, 62 66878 2-acetamido-3-0 - {(l-1- (D-carbamoyl-3-carboxy-propyl) -N-methyl-carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose; 2-acetamino-3-O- (D1 - ((D1-carbamoyl-3-carboxypropyl) -carbamoylmethyl) -N-methylcarbamoyl-ethyl} -2-deoxy-D-glucose, 2- benzoylamino-3-O-11) -1 - ((D1-carbamoyl-3-carboxy-propyl) -carbamoyl-methyl) -N-methyl-carbamoyl-ethyl} -2-deoxy-D-Glucose, 2- acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-ethyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2- acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-methyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (L- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzamido-3-O- {D1- ( 1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -N-ethyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {Dl - (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -N-propyl-carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1- 1- (D1-Carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-benzoylamino-3- O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-N, N-pentamethylene) -carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino- 3-O- [D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -N-methyl-carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2- acetamido-3-0 - ((L-1- (D-carbamoyl-3-carbo xy-methyl-phenyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O - ((1- 1- (D1-carbamoyl-3-carboxymethyl-phenyl) - carbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - ((1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-2-methylmercaptoethyl) ) -carbamoylmethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-2-chloroethyl) - carbamoylmethyl} -2-deoxy-D-glucose, 2-acetamino-3- (O- (D1- (1- 1- (D1-carbamoyl-3,3-dicarboxypropyl) carbamoylethyl) carbamoyl ethyl) } -2-deoxy-D-glucose, 2- (6-carbomethoxy-succinamido) -3-O - ((1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl -methyl} -2-deoxy-D-glucose, 2- (3-carbomethoxy-succinamido) -3-O- {D1- (1- 1- (D1-carbamoyl-3-636,6878 carboxypropyl) -carbamoyl- Ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-benzamino-3-O - {(L-1- (D1-carbamoyl-3-trimethylsilylcarboxy-propyl) -carbamoyl-ethyl) -carbamoyl 1-methyl} -2-deoxy-1,4,6-tris-trimethylsilyl-D-glucose (the trimethylsilyl ester group is rapidly saponified on contact with water), 2-acetamino-2-deoxy-3-O - {(1-1 - (D1-Carbamoyl-3-trimethylsilyl-carboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} -1,4,6-tris-trimethylsilyl-D-glucose, 2-acetamino-3-O- {D1- (L -1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-3-O- {D1- (1-1 - (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-2'-hydroxy-propyl) -carbamoyl-ethyl} -2-deoxy-D-Glucose, 2-acetamino-3-O- {Dl - (l-1- (D-carbamoyl-3-carboxy-propyl) -carboxylic-carbamoyl-21- (p-hydroxy-phenyl) ethyl) carbamoyl} -2-ethyl-des-oxy-D-glucose; 2-acetamido-3-0- {DL- (L-1- (D-carbamoyl-3-carboxy-propyl) -carboxylic-carbamoyl-n, n-tetramethylene) -carbamoyl-ethyl} -2-deoxy-D- glucose, 2-glycolylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose oose, 2-glycolylamino-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N -methyl-acetamino) -3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2- (N-methyl-acetamino) -3-O- (D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl> -2-deoxy-D-glucose, 2-acetamido-3-0- {DL- (l-1- (D-carbamoyl-3-carboxy-propyl) -carboxylic-carbamoyl-2'-phenylethyl) -carbamoyl-ethyl} -2-deoxy-D-glucose , 2-acetamino-3-O - {(L-1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-2 '- (p-hydroxyphenyl) ethyl) carbamoylmethyl} -2- deoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1- (L1-carboxy-ethyl) -carbamoyl-3-benzylcarboxy-propyl) -carbamoyl-ethyl) -carbamoylmethyl} - 2-desoxy-D-glucose, 2-acetamino-3-O - {(L-1- (D1,3-dicarboxypropyl) -N-methylcarbamoyl-ethyl) -carbamoylmethyl} - 2-deoxy-D-glucose.

Several of the aforementioned muramyl peptides or their spacer-linked forms are novel. They can be prepared, for example, as shown in the following examples: 64 66878

Example 38;

A solution of 3.4 g of benzyl-2-acetamino-3-O- (D-1- {L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl- 1-ethyl} -carbamoyl-ethyl] -2-deoxy-αD-glucopyranoside benzyl ester in 100 ml of methanol / distilled water 2/1, hydrogenated as a catalyst 0.3 g of 10% palladium on carbon, at normal pressure and 45 ° The catalyst is filtered off and the filtrate is evaporated, the residue is dissolved in 40 ml of water and this solution is extracted 3 times with 40 ml of water-saturated sec-butanol each time and the organic phases are washed 3 more times. The aqueous solution is combined, evaporated, the residue is dissolved in a small amount of distilled water and freeze-dried to give 2-acetamino-3-O- [1- [1- (1-) -carbamoyl- 3- (11-Carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-ethyl-2-deoxy-D-glucose as a white powder with (a) D = + 9 ° + 1 ° (distilled water, c = 1.090).

The starting material used is prepared as follows:

To a solution of 6.1 g of benzyl-2-acetamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} - 2-deoxy-αD-glucopyranoside monohydrate and 3.5 g of L-alanine benzyl ester p-toluenesulfonate in 30 ml of N, N-dimethylformamide, 1.4 ml of triethylamine, 1.1 g of N-hydroxysuccinyl imide and 2.3 g of dicyclohexylcarboximide and stirred for 48 hours at room temperature. The crystallized dicyclohexylurea is filtered off and washed with 10 ml of N, N-dimethylformamide and the filtrate is evaporated to dryness. The residue is suspended in 100 ml of water, stirred for 1 hour at 0 °, the insoluble matter is filtered off, washed with a small amount of ice water and dried. The product is further dissolved in methanol, precipitated with twice the amount of ethyl acetate, filtered, washed with a small amount of ethyl acetate and dried: (a) ^ = + 72 ° + 1 ° (methanol, c = 0.998).

In a similar manner, starting from benzyl 2-acetamino-3-O-1- (1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-α-D-glucopyranoside 2 -acetamino-3-O- {{L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -1'-carbamoyl-ethyl} -carbamoyl-methyl'-2-deoxy-D glucose are.

Starting from benzyl 3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} -2-deoxy-2-propionamino-αD-glucopyranoside and glycine benzyl ester p-toluene-65,6878 sulfonate is prepared from 3-O- (D1- (L1-) D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl {carbamoyl-ethyl] -2 -desoksi-2-propioniamino-D-glucose.

Correspondingly prepared: 2-acetamino-3-O- [{1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl} carbamoylmethyl} -2-deoxy-D- glucose, 2-butyrylamino-3-O- [1- [L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-ethyl ] -2-deoxy-D-glucose, 2-butyrylamino-3-O- [{1- (D1-carbamoyl-3- (L1-carboxyethylcarbamoyl) propyl) carbamoyl-ethyl} -carbamoylmethyl] -2-deoxy-D-glucose, 3-O-1- {L1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl {carbamoylmethyl] -2-deoxy-2 -propionamino-D-glucose, 2-iso-butyrylamino-3-O- {L1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-propyl {-carbamoyl-methyl] -2-deoxy-D-glucose, 2-iso-butyrylamino-3-O- [1--L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl -propyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-iso-butyrylamino-3-O-{{1 - ( D1-Carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-2-methylpropyl {-carbamoylmethyl] -2-deoxy-D-glucose, 2-iso-butyrylamino-3-O - | d-1- {L-1- (d-carbamoyl-3- (ll-carboxy-ethyl-carbamoyl) propyl) carbamoyl-2-methylpropyl -carbamic {-sulfamoyl-ethyl-2-d-desokjsi glucose, 2-iso-butyrylamino-3-O- {L1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl {carbamoylmethyl] -2-deoxy-D- glucose, 2-iso-butyrylamino-3-O- {L1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl {carbamoylmethyl] -2-deoxy-D- glucose, 2-iso-butyrylamino-3-O- [1- [L-1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl} -carbamoyl-ethyl] - 2-deoxy-D-glucose, 2-iso-butyrylamino-3-O- {L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-ethyl { -carbamoyl-methyl] -2-deoxy-D-glucose, 66 66878 2-iso-butyrylamino-3-O- [1--L- -Carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-iso-butyrylamino-3-O- {L-1 - (D1-carbamoyl-3- (L1-carboxy-propyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl] -2-deoxy-D-glucose, 2-acetamino-3-O- | {L-1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-2-methylpropyl} carbamoylmethyl] -2-deoxy-D-glucose, 2-acetamino-3- 0 | {d-1 of L-1- (d-carbamoyl-3- (carboxy-methyl-carbamoyl) propyl) carbamoyl-2-methylpropyl} carbamoyl-ethyl-lij-2-deoxy-d -glucose, 2-acetamino-3-O- {L1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-2-methylpropyl} -carbamoyl-methyl | 2-deoxy-D-glucose, 2-acetamino-3-O- [1- [1- (D1-carbamoyl-3- (L1-carboxyethylcarbamoyl) propyl) carbamoyl-2-methylpropyl } -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-acetamino-3-O- {L-1- (D1-carbamoyl-3- (L1-carboxy-propyl-carbamate) (yl) -propyl) -carbamoyl-2-methyl-propyl} -carbamoyl-methyl-2-deoxy-D-glucose, 2-butyrylamino-3-O- [L1- (D1-carbamoyl-3- (Ll) -carboxy-butyl-1-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl] -2-deoxy-D-glucose, 2-acetamino-3-O- [1- [1- [1- -Carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-propyl} -carbamoyl-ethyl} -2-deoxy-D-glucose, 2-acetamino-1,5-O- {L1- (D1 -Carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-propyl} -carbamoyl-methyl} -2-desoxy-D-glucose, 2-acetamino-3-O- 1- {L-1- (D1-Carbamoyl-3- (carboxymethyl-carbamoyl) -propyl) -carbamoyl-propyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-acetamino-3-O -j {L1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoylpropyl} carbamoylmethyl | -2-deoxy-D-glucose, 2-acetamino-3-O - | {L-1- (D-carbamoyl-3- (ll-carboxy-propyl-carbamoyl) propyl) carbamoyl ethyl} carbamoyl-2-metyylij-des-ok si-D-glucose, 67 66878 2-acetamino-3-O- [1--1- {L1- (D1-carbamoyl-3- (L1-carboxy-propyl-carbamoyl) -propyl) -carbamoyl-ethyl] -carbamoyl- ethyl-2-deoxy-D-glucose, 2-acetamino-3-O-L1- (D1-carbamoyl-3- (L1-carboxy-2-methylpropylcarbamoyl) -propyl) -carbamoyl-ethyl] -carbamoyl- methyl -2-deoxy-D-glucose, 2-acetamino-3-O- [1- [1- (D1-carbamoyl-3- (L1-carboxy-2-methyl-propyl-carbamoyl) -propyl]) -carbamoyl-ethyl} -carbamoyl-ethyl-2-deoxy-D-glucose, 2-acetamino-3-O - ({L1- (D1-carbamoyl-3-) L-1-carboxy-butyl-carboxylate) (M -oyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl] -2-deoxy-D-glucose, 2-butyrylamino-3-O- {L1- (D1-carbamoyl-3- (carboxymethyl-carbo) -bamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl] -2-desoxy-D-glucose, 2-butyrylamino-3-O- (d-1- {L1- (D1-carbamoyl-3- ( (11-carboxy-propyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-butyrylamino-3-O- ({L1- (D1-carbamoyl-3- (L1-carboxy-propyl-1H-carbamoyl) -propyl) -carbamoyl-ethyl] -carbamoyl-methyl] -2-deoxy-D-glucose, 2-butyrylamino-3- O- [1- 1- {L-1- (D1-carbamoyl-3- (L1-carboxy-2-methyl-propyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-ethyl} -2-deoxy- glucose, 2-butyrylamino-3-O- {{1- (D1-carbamoyl-3- (L1-carboxy-2-methyl-propyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoylmethyl} -2 -deoxy-D-glucose, N-2-benzoylamino-3-O- {L1- (D1-carbamoyl-3- (L-1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- [1--L-1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-ethyl} - carbamoyl-ethyl-2-deoxy-D-glucose, 2-benzoylamino-3-O- {L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-propyl} -Carbamoyl-methyl-2-deoxy-D-glucose, 2-benzoylamino-3-O- [1--L-1- (D1-carbamoyl- 3- (Carboxymethyl-carbamoyl) -propyl) -carbamoyl-propyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 68 66878 2-acetamino-3-O-j {L1- (D1-carbamoyl-3 - (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-N, N-tetramethylene} -carbamoyl-methyl] -2-deoxy-D-glucose, 2-acetamino-3-O- 1- {L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-N, N-tetramethylene} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2- acetamido-3-0-j {LL (D-carbamoyl-3- (carboxy-methyl-carbamoyl) propyl) carbamoyl, n, n-tetramethylene-metyylij} carbamoyl-2-deoxy-D-glucose , 2-acetamino-3-O- [1- {L-1- (D1-carbamoyl-3- (carboxymethylcarbamoyl) propyl) carbamoyl-N / N-tetramethylene} carbamoyl- Ethyl--2-deoxy-D-glucose, N-2-acetamino-3-O- {L-1- (D1-carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl -2-hydroxy-ethyl} -carbamoyl-methyl-1 H-2-deoxy-D-glucose, 2-acetamino-3-O- [1--1- {L-1- (D1-carbamoyl-3- (L1- carboxy-ethyl-ka (rbamoyl) -propyl) -carbamoyl-2-hydroxy-ethyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-benzoylamino-3-O- [{L- (D1-carbamoyl-3- (L1-carboxy) (ethyl-carbamoyl) -propyl) -carbamoyl-2-hydroxy-ethyl} -carbamoyl-methyl} -2-deoxy-D-glucose, 2-benzoylamino-3-O- [1--1- {L-1- (Dl -Carbamoyl-3- (L1-carboxy-ethyl-carbamoyl) -propyl) -carbamoyl-2-hydroxy-ethyl} -carbamoyl-ethyl] -2-deoxy-D-glucose, 2-acetamino-3-O-j {L1- (D1-Carbamoyl-3- (L-1-carboxymethyl) -carbamoyl-propyl) -carbamoylmethyl} -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetamino-3- 0 | {d-1 of L-1- (d-carbamoyl-3- (L-carboxy-methyl-carbamoyl) propyl) carbamoyl-methyl} carbamoyl-ethyl-2-deoxy-d-glucose , 2-acetamino-3-O- {L-1- (D1-carbamoyl-3- (L1-carboxymethylcarbamoyl) propyl) carbamoylmethyl} carbamoylmethyl} -2-deoxy- D-glucose, 2-acetamino-3-O- [1--1- {L-1- (D1-carbamoyl-3- (L1-carboxymethylcarbamoyl) propyl) carbamoylmethyl} -t arbamoyl-ethyl-2-deoxy-D-glucose, 2-acetamino-3-O- {L-1- (D1-carbamoyl-3- (L1-carboxymethyl-carbamoyl) -propyl) -carbamoyl- methyl} carbamoyl-methyl | -2-deoxy-D-glucose.

69 66878

Example 39:

Solution of 4.2 g of benzyl-2-acetamino-3-O- {{1- (β-1-carbamoyl-3- (L-5-benzyloxycarbonylamino-5-carbamoyl-pentylcarbamoyl)) propyl ) -carbamoyl-ethyl} -carbamoyl-methyl-2-deoxy-αD-glucopyranoside in 100 ml of methanol / water 2/1, hydrogenated as a catalyst by 0.5 g of 10% palladium / carbon, under normal pressure and at room temperature. In this case, the pH of the reaction mixture is maintained at 6 by adding 1N hydrochloric acid. After uptake of hydrogen, the catalyst is filtered off and the filtrate is evaporated to dryness. The residue is dissolved in a small amount of distilled water and lyophilized.

2-Acetamino-3-O- {L-1- (D1-carbamoyl-3- (L-5-amino-5-carbamoyl-pentyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl is obtained. 1-methyl-2-deoxy-D-glucose hydrochloride as a white powder.

The starting material used can be prepared as follows:

A solution of 15 g of α-carbobenzoxy-e-t-butoxycarbonyl-L-lysine methyl ester in 100 ml of saturated methanolic ammonia solution is left to stand for 48 hours at room temperature and evaporated to dryness. The product, α-carbobenzoyl-e-t-butoxycarbonyl-L-lysinamide, is recrystallized from methanol / ether, m.p. 142 °, (α) D = -3 ° + 1 ° (methanol, c = 1.018).

A solution of 3 g of α-carbobenzoxy-s-t-butyloxycarbonyl-1-L-lysinamide in 25 ml of trifluoroacetic acid, cooled to 0 °, is stirred for 1 hour and then evaporated to dryness. To the residue are added 20 ml of saturated brine and ice, made alkaline with concentrated ammonia solution and extracted with ethyl acetate. The organic phase is washed with further saturated brine, dried over sodium sulfate and evaporated to dryness. Obtained α-carbobenzoxy-L-lysinamide as a white foam.

To a solution of 5.6 g of benzyl-2-acetamino-3-O- {{1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl} -carbamoyl-methyl] -2-deoxy-αD -glucopyranoside and 2.8 g of α-carbobenzoxy-L-lysinamide in 30 ml of Ν, Ν-dimethylformamide, 1.1 g of N-hydroxysuccinimide and 2.2 g of dicyclohexylcarbodiimide are added and the mixture is stirred for 40 hours at room temperature. The crystallized dicyclohexylurea is filtered off and washed with 10 ml of Ν, Ν-dimethylformamide. The filtrate is evaporated to dryness and the residue is extracted for 30 minutes with 100 ml of distilled water. The insoluble matter is filtered off, washed with water, dried to give benzyl-2-acetamino-3-O- {L-1- (D1-carbamoyl-3- (L-5-benzyloxycarbonylamino) -70,6878 -5-carbamoyl- pentyl-carbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl] -2-deoxy-αD-glucopyranoside. The product is recrystallized from methanol / ethyl acetate.

Correspondingly prepared: 2-acetamino-3-O- {{1- (D1-carbamoyl-3- (5-amino-1β-carbamoyl-pentylcarbamoyl) -propyl) -carbamoyl-ethyl} -carbamoyl-methyl} 2-deoxy-D-glucose hydrochloride.

Example 40:

Solution of 2.8 g of benzyl-3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-methyl} -2-deoxy-2 -isobutyroylamino-α-glucopyranoside in 80 ml of methanol / distilled water 1/1, hydrogenated, catalyst 0.3 g of 10% palladium / carbon, at normal pressure and 45 °. After further treatment and freeze-drying of the residue, 3-O - ((1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-methyl} -2-deoxy-2-isobutyroylamino-D- glucose as a white powder.

The starting material used is prepared as follows:

A mixture of solutions of 21.0 g of benzyl 2-amino-2-deoxy-4,6-O-isopropylidene-α-glucopyranoside in 150 ml of chloroform and 9.0 g of potassium hydrogen carbonate in 150 ml of distilled water is cooled while with stirring, to 0 ° and 8.5 ml of iso-butyric acid chloride are added dropwise. After stirring for 1 hour at room temperature, the organic phase is separated off, washed with ice-cold 0.5N hydrochloric acid, water, saturated sodium hydrogen carbonate solution and again with water, dried and evaporated. The product, benzyl 2-deoxy-2-isobutylamino-4,6-O-isopropylidene-α-D-glucopyranoside, is crystallized from 150 ml of ether, m.p. 82 °, (α) D = + 109 ° + 1 ° (chloroform, c = 1.017).

To a solution of 15.1 g of benzyl 2-deoxy-2-isobutyroylamino-4,6-O-isopropylidene-α-glucopyranoside in 150 ml of absolute acetonitrile is added, under a nitrogen atmosphere while protecting from moisture and stirring, 1.9 g of sodium hydride (Fluka, pract.) and stir for 1.5 hours at 40 °. The reaction mixture is then cooled to -10 ° and 5.6 ml of methyl bromoacetate are added. Stir for an additional 15 minutes in an ice bath and an additional 2 hours at room temperature. After further work-up, benzyl 2-deoxy-2-isobutylamino-4,6-O-isopropylidene-3-O-methoxycarbonylmethyl-α-D-glucopyranoside is obtained, which is recrystallized from ether-66878 71 ri / petroleum ether, m.p. 119-120 °, (α) D = + 152 ° + 1 ° (chloroform, c = 0.963).

A solution of 3.16 g of benzyl 2-deoxy-2-isobutyrylamino-4,6-O-isopropylidene-3-O-methoxycarbonylmethyl-α-glucopyranoside in 30 ml of methanol and 10 ml of 1N sodium hydroxide solution, left to stand at room temperature for 1 hour. 3 ml of 1N hydrochloric acid are added and the solution is evaporated to dryness. The residue is dissolved in 50 ml of Ν, Ν-dimethylformamide and 2.26 g of L-α-aminobutyroyl-D-iso-glutamine-tert-butyl ester hydrochloride and 1.75 g of EEDQ are added and left to stand for 24 hours at room temperature. . An additional 0.2 g of EEDQ is added and the mixture is allowed to stand for a further 24 hours. The solvent is distilled off and the residue is dissolved in ethyl acetate / water. The organic phase is separated and washed with ice-cold 1N hydrochloric acid, water, saturated sodium hydrogen carbonate solution and water, dried over sodium sulfate and evaporated to dryness. There is thus obtained benzyl 3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-1-propyl) -carbamoylmethyl} -2-deoxy-2-isobutylamino-4,6- O-isopropylidene-αD-glucopyranoside tert-butyl ester as a white foam.

This product is dissolved in 60 ml of glacial acetic acid, while adding 60 ml of water with stirring, and left to stand for 24 hours at room temperature. This solution is evaporated to dryness in a water-jet vacuum and the residue is dissolved in ethanol. Filter with activated carbon and evaporate to dryness again. There is thus obtained benzyl 3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -carbamoyl-1-methyl} -2-deoxy-2-isobutyroylamino-αD-glucopyranoside- tert-butyl ester, a white amorphous substance with (a) D = + 74 ° + 1 ° (methanol, c = 0.950).

A solution of 3.9 g of this tert-butyl ester in 40 ml of 98% trifluoroacetic acid, cooled to 0 °, is stirred for 1 hour at 0 ° and poured into 500 ml of absolute ether. The crystallized product is filtered off, washed with ether and dried in vacuo. The obtained powder is dissolved in 40 ml of water / tetrahydrofuran 1/1 and stirred for 30 minutes with 50 ml of Dowex 3 ion exchange resin (acetate form). The ion exchange resin is filtered off and washed with 500 ml of tetrahydrofuran / 1-acetic acid. The filtrate is evaporated to dryness and the product is crystallized from methanol / ether, m.p. 205-206 °.

72 66878

Example 41;

A solution of 3.1 g of benzyl-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-2-isobutyroylamino- αD-glucopyranoside in 40 ml methanol / water 1/1, hydrogenated with 10% palladium / carbon, at normal pressure and 45 °. After further work-up, 3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-2-iso-butyrylamino-white powder is obtained as a white powder by freeze-drying. D-glucose.

The starting material used is prepared in the same manner as in Example 40:

Condensation of benzyl-3-O-carboxymethyl-2-deoxy-2-isobutyroylamino-4,6-O-isopropylidene-αD-glucopyranoside sodium salt with L-alanyl-D-isoglutamine-tert-butyl ester hydrochloride gives benzylic acid. 3-0 - {(L-1- (D-carbamoyl-3-carboxy-pro-propyl) carbamoyl-ethyl) -carbamoyl-methyl} -2-desoxy-2-isobutyraldehyde royyliamino-4,6-O- isopropylidene-αD-glucopyranoside tert-butyl ester which is a white foam. Hydrolysis of the 4,6-O-isopropylidene group affords benzyl 3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-2 -isobutyroyl-20-amino-α-glucopyranoside tert-butyl ester with (a) D = + 71 ° + 1 ° (methanol, c = 0.956).

The tert-butyl ester is cleaved off with trifluoroacetic acid. There is thus obtained benzyl 3-O - {(L1- (D1-carbamoyl-3-carboxypropyl) carbamoyl-ethyl) -carbamoylmethyl} -2-deoxy-2-isobutyroylamino-α-glucopyranoside as a white amorphous product. .

Example 42:

Solution of 4.2 g of benzyl-2-acetyl-N-methyl-amino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl -methyl} -2-deoxy-D-glucopyranoside in 75 ml of methanol / water 1/1, hydrogenated with 0.5 g of 10% palladium / carbon at normal pressure and 45 °. The catalyst is filtered off and the filtrate is evaporated to dryness. The residue is dissolved in a small amount of distilled water and lyophilized. This gives 2-acetyl-N-methylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoylmethyl} -2-deoxy-D- glucose as a white powder.

The starting material used is prepared as follows:

To a solution of 8.5 g of benzyl-2-acetamino-2-deoxy-4,6-O-isopropylidene-3-O-methoxycarbonylmethyl-α-glucopyranoside 73 66878 in 80 inches of absolute acetonitrile is added under a nitrogen atmosphere to the mixture with stirring and humidity. 0.75 g of sodium hydride (Fluka, pract.) And stir for 1 hour at 40 °. The reaction mixture is then cooled to room temperature and a solution of 6.0 g of methyl iodide in 50 ml of absolute acetonitrile is added dropwise over 4 hours. After 3 hours, the reaction mixture is filtered and the filtrate is evaporated to dryness. The residue is dissolved in ethyl acetate, this solution is washed with water, dried over sodium sulfate and evaporated to dryness. Benzyl 2-acetyl-N-methylamino-2-deoxy-4,6-O-isopropylidene-3-O-methoxycarbonyl-methyl-α-glucopyranoside is obtained as a yellowish oil with an Rf value of 0.45 silicon. -acid-thin layer plate in the system methylene chloride / ethyl acetate 85/15.

A solution of 4.4 g of benzyl 2-acetyl-N-methylamino-2-deoxy-4,6-O-isopropylidene-3-O-methoxycarbonylmethyl-α-glucopyranoside in 60 ml of methanol and 15 ml of ml of 1N sodium hydroxide solution, leave to stand for 1 hour at room temperature, add 5 ml of 1N hydrochloric acid and evaporate to dryness. The resulting benzyl 2-acetyl-N-methylamino-3-O-carboxymethyl-2-deoxy-4,6-O-isopropylidene-α-glucopyranoside sodium salt is dissolved in 50 ml of N, N-dimethylformamide and condensed with 3.2 g of L-alanyl-D-isoglutamine-tert-butyl ester hydrochloride in the presence of 2.5 g of EEDQ. The solution is evaporated to dryness in vacuo and the residue is dissolved in ethyl acetate. The solution is washed with water, ice-cold 1N hydrochloric acid, water, saturated sodium hydrogen carbonate solution and water, dried over magnesium sulphate and evaporated to dryness. Benzyl-2-acetyl-N-methylamino-3-O - {(1-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoylethyl) -carbamoyl-methyl} -2-deoxy-4 is obtained. , 6-O-isopropylidene-αD-glucopyranoside tert-butyl ester as a yellowish foam. This product is dissolved in 45 ml of 95% trifluoroacetic acid pre-cooled to 0 ° and stirred for 1 hour at 0 °. The reaction mixture is poured into 400 ml of absolute ether, the precipitated product is filtered off, washed with ether and dried. Treatment of this material with an ion exchange resin, Dowex-3-acetate form, gives trifluoroacetic acid-free benzyl-2-acetyl-N-methylamino-3-β-β (1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoylethyl) -carbamoyl-methyl} -2-deoxy-αD-glucopyranoside as a white powder.

In a similar manner there are prepared: 74 66878 2-Acetyl-N-methylamino-3-O- {D1- (L-1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-ethyl) -carbamoyl-ethyl} - 2-deoxy-D-glucose, 2-acetyl-N-methylamino-3-O- {D1- (1- 1- (D1-carbamoyl-3-carboxypropyl) carbamoylpropyl) carbamoyl -ethyl} -2-deoxy-D-Glucose, 2-acetyl-N-methylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) -carbamoyl-propyl) -Carbamoyl-methyl} -2-deoxy-D-Glucose, 2-acetyl-N-methylamino-3-O - {(1- 1- (D1-carbamoyl-3-carboxy-propyl) - carbamoyl-2-methyl-propyl) -carbamoyl-methyl} -2-deoxy-D-glucose, 2-acetyl-N-methylamino-3-O- {D1- (L-1- (D1-carbamoyl-3) -carboxy-propyl) -carbamoyl-21-methyl-propyl) -carbamoyl-ethyl} -2-deoxy-D-glucose, 3-O - {(L-1- (D1-carbamoyl-3-carboxy-propyl) - carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-2-propionyl-N-methylamino-D-Glucose, 2-butyryl-N-methylamino-3-O - ((1- (D-carbamoyl-3-carboxy-propyl) carbamoyl-ethyl) -carbamoyl-methyl} -2-deoxy-D-Glu-koosia.

Example 43:

Trimethylsilyl ether can be prepared, for example, as follows: 0.3 g of 2-benzamido-2-deoxy-3-O - {(1- 1- (D1-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl) -carbamoyl-methyl} D-glucose is dissolved in 3 ml of dimethylformamide and 0.4 ml of bis-trimethylsilylacetamide is added. After 5 hours at 35 °, evaporate in vacuo to a syrup from which the acetamide formed can be separated by dissolving in absolute ether or absolute ethyl acetate. After re-evaporation, a colorless syrup is obtained with (a) D = + 15 ° (c = 0.1, dioxane).

Similarly, a syrupy 2-acetamino-2-deoxy-3-O - {(1-1- (D1-carbamoyl-3-trimethylsilylcarboxypropyl) carbamoylethyl) carbamoylmethyl} -1,4,6-tri -trimethylsilyl-D-Gluose with (a) ^ = -10 ° (c = 0.91, dioxane).

Upon contact with water, the trimethylsilyl ester group is rapidly saponified so that these derivatives are also suitable for coupling.

66878

Example 44:

Benzyl 2-acetamido-3-0-j {LL (d-1- (L-carboxy-ethyl) -carboxylic-carbamoyl-3-carboxypropyl) carbamoyl-ethyl} -carbamoyl-methyl-lij-2-desoxy A 5% solution of α-glucopyranoside in tetrahydrofuran / water 2/1 is hydrogenated as a catalyst with 10% palladium / carbon at normal pressure and room temperature. After uptake of the theoretical amount of hydrogen, the catalyst is filtered off and the filtrate is freeze-dried. This gives 2-acetamido-3-O-{{L- (d-1- (L1-carboxy-ethyl) -carbamoyl-3-carboxypropyl) -carbamoyl-ethyl} -carbamoyl-methyl} -2-deoxy-D-glucose. as a white powder. Rf value in thin layer chromatogram = 0.21 (acetic acid ethyl ester / n-butanol / pyridine / acetic acid / water 42: 21: 21: 6: 10).

In a similar manner, a derivative is prepared with authentic muramic acid.

The starting material can be prepared as follows: 5.68 g of N-tert-butoxycarbonyl-L-alanyl-Dy-benzyl-Glu-tamyl-L-alanine benzyl ester are dissolved in a mixture of 5 ml of trifluoroacetic acid and 5 ml of 1,2-dichloroethane and left stand for 16 hours at room temperature, protected from moisture. Dilute this solution with 50 ml of tetrahydrofuran, cool in an ice bath and neutralize with triethylamine. After the addition of a solution of 3.7 g of benzyl 2-acetamido-3-carboxymethyl-2-deoxy-α-glucopyranoside and 1.38 ml of triethylamine in 100 ml of tetrahydrofuran, 2.6 g of 2 -ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline and allowed to stand for 24 hours at room temperature. After evaporation of the solvent, the residue is dissolved in chloroform / methanol 9/1, washed with water, ice-cold 2N hydrochloric acid, water, saturated sodium hydrogencarbonate solution and water, filtered and the solvent is removed. There is thus obtained benzyl-2-acetamido-3-O- {1- (1--1- (1-carboxyethyl) carbamoyl-3-carboxypropyl) carbamoylethyl} carbamoylmethyl} -2 -deoxy-α-D-glucopyranoside as a colorless powder, Rf value = 0.48 (in an identical system).

The starting material used can be prepared as follows: 7.15 g of N-tert-butoxycarbonyl-L-alanyl-D-glutamic acid γ-benzyl ester and 6.15 g of L-alanine benzyl ester p-toluenesulfonate are dissolved in 100 ml of anhydrous dimethylformamide. Cool in an ice bath and add, with stirring, successively 4.03 g of N-hydroxysuccinimide, 3.61 g of dicyclohexylcarbodiimide and finally 1.95 ml of N-methylmorpholine. After stirring for 6 hours at 0 ° and 15 hours at room temperature, the suspension is cooled, the precipitate (dicyclohexylurea and morpholine hydrochloride) is filtered off and the filtrate is evaporated. The residue is dissolved in ethyl acetate, washed several times with water, 1N citric acid and 1N sodium hydrogen carbonate solution and further with water. The vinegar-ester solution is dried, evaporated and the crystalline residue is recrystallized from ethyl acetate / petroleum ether 1/1, m.p. 135-136 °, (α) D = -9 ° + 1 ° (c = 1, methanol), Rf = 0.82 (in the above system) and 0.86 (acetonitrile / water 3: 1).

Instead of alanine, the protected dipeptide can be correspondingly extended by other natural amino acids.

Example 45: g 7.5 x 10 dead Trypanosoma cruzi parasites (Chagas disease agent) are suspended in a solution of 50 mg of 2-acetamino-3-Oj (L1- (D-carbamoyl-3-carboxypropyl) -carbamoyl-ethyl). ) -carbamoylmethyl] -2-deoxy-D-glucose-N-hydroxysuccinimide ester in 6 ml of physiological buffer. The suspension is incubated for two hours at 37 °. The muramyl peptide-conjugated parasites are then precipitated by centrifugation. The precipitate is washed by resuspending it in physiological spray solution and recentrifuging. The washed parasite-muramyl peptide conjugates are suspended in physiological spray solution and used for immunization.

The quantitative determination of murpanyl peptide coupled to trypanosomes is performed as in Example 1 by the Morgan-Elson reaction to give 50-70 mg of muramyl peptide per mg of trypanosomes.

Claims (8)

77 66878 A process for the preparation of novel antigen derivatives comprising an antigen to which at least one and at most as many muramyl peptide molecules per antigen molecule are bound so that the antigenic nature is retained, and optionally bridging members and a carrier, wherein the unbound muramyl peptide has the formula II structure CH2OR6 vi> * '! N - x - r2 (II) r3 - ch (D) r13 \ * 8 flO fu CON - CH - CON - CH - CH2CH - R12 wherein 17 © R, © X is a carbonyl or carbonyloxy group,, R4 and Rg are separated independently hydrogen or trimethylsilyl, R 2 is a phenyl residue or unsubstituted or lower alkyl substituted by hydroxy, carboxy, lower alkoxy and / or lower alkoxycarbonyl, R 8, R 7 # R 9 and R 2 are independently hydrogen or lower alkyl, R 8 is hydrogen, unsubstituted or , lower alkyl substituted with amino, mercapto or phenyl residue, or Ry and Rg together are alkylene # having 3 or 4 carbon atoms, and R10, R1 and 2 are independently carboxy, trimethylsilyloxycarbonyl, unsubstituted or phenyl-substituted lower alkoxycarbonyl, carboxyl, or is unsubstituted or substituted on the nitrogen atom by unsubstituted or carboxy, lower alkoxycarbonyl or carbamoyl-substituted lower alkyl , or R 1 is also hydrogen, provided that at least one free hydroxy, amino, mercapto or carboxy group is present in the starting compound of formula II, characterized in that the antigen optionally attached to the bridging members is condensed by forming covalent bonds oxycarbonyl. with iminocarbonyl or carbonylthio groups, optionally to bridging members of muramyl peptides of the formula II, one of which has at least one free amino, hydroxy and / or mercapto group and the other at least one carboxylic acid group, and the compound obtained as described above if desired, it is also condensed by forming covalent bonds with oxycarbonyl, iminocarbonyl or carbonylthio groups, optionally on a support bonded to the bridge members. Process according to Claim 1, characterized in that a muramyl peptide of the formula II is used, in which hydrogen is indicated and the other substituents have the meanings given in claim 1. Process according to Claim 1 or 2, characterized in that the second compound is reacted in the form of an activated carboxylic acid with the second compound in the form of a free amino, hydroxy or mercapto compound. Process according to one of Claims 1 to 3, characterized in that the carboxylic acid component is activated by esterification with N-hydroxysuccinimide before condensation. Process according to one of Claims 1 to 4, characterized in that a high molecular weight polymer of lactic acid or its derivatives containing a free carboxyl group at the chain end, alginic acid, polygalacturonic acid, pectin, carboxymethylcellulose or agarose, agarose, agar is used as the carrier according to claim 1. acidic polyamic acid. Process according to one of Claims 1 to 5, characterized in that the bridging member is an α, ω-diamino-lower alkane, an alkane dicarbonyl or an aminoalkanecarbonyl bonded via a nitrogen atom from which the bond leaves the nitrogen atom. Process according to one of Claims 1 to 4, characterized in that the muramyl peptide of the formula I according to Claim 1 is used, in which R 1, R 8, R 4 and R 4 are hydrogen, X is carbonyl, R 2 is phenyl or, optionally, by hydroxy or Alem - 79 66878 lower alkyl substituted by pialkoxy, and denotes hydrogen or methyl and R 9, R 8 / R 10, R 1 -j and R 12 have the same meaning as in Claim 1. Process according to one of Claims 1 to 4, characterized in that the muramyl peptide of the formula II according to Claim 1 is used, in which R 1, R 2, R 8, R 2, R 8 and R 1 are hydrogen, X is carbonyl, R 2 is phenyl or optionally by hydroxy. or lower alkyl substituted with nitoxy, R 1 is hydrogen or methyl, R 8 is lower alkyl, hydroxy-lower alkyl or phenyl and R 1, R 1 and R 2 and R 2 are carboxyl, lower alkoxycarbonyl or carbamoyl or R 1 is also hydrogen.