MXPA01010624A - Novel ribose-substituted aromatic amides, method for the production and use thereof as medicaments - Google Patents

Abstract

Compounds of formula (I);wherein R1=alkyl, alkenyl or alkynyl, O-alkyl, O-alkenyl or optionally substituted, optionally interrupted O-alkynyl;R2=hydrogen or halogen;R3=hydrogen, alkyl or halogen;R4=NHR'or NHOR'', R'or R''are identical or different and represent hydrogen, alkyl, alkenyl or alkynyl, aryl;R5=hydrogen or O-alkyl;R6=alkyl or CH2-O-alkyl;R7=hydrogen or alkyl or R6 et R7 form a cycle together with the carbon carrying them in addition to the additionsalts thereof with bases. The compounds of formula (I) have antibiotic properties.

Description

NEW AROMATIC AMIDAS REPLACED BY A RIBOSA, METHOD FOR THE PRODUCTION AND USE OF THE SAME AS MEDICINES The present invention relates to novel aromatic amides substituted by a ribose, its preparation process and its application as medicaments. The subject of the invention is the compounds of the formula (I): wherein Ri 'represents an alkyl, alkenyl or alkynyl, 0-alkyl, O-alkenyl or linear, branched or cyclic O-alkynyl containing up to 8 carbon atoms optionally substituted by one or more halogen atoms, optionally interrupted by an oxygen, sulfur or nitrogen atom, an aryl or aralkyl radical that REF: 133814 contains up to 18 optionally substituted carbon atoms, an optionally substituted monocyclic or polycyclic aromatic heterocyclic radical, an NH 2 radical, NHalcyl or NHalc 2, NHalc 3 or NHOalc 4, alk, alc 2, alc 3 and alc 4 representing an alkyl radical that contains up to 8 carbon atoms, R 2 represents a hydrogen atom or a halogen atom, R 3 represents a hydrogen atom, an alkyl radical containing up to 8 carbon atoms or a halogen atom, R 4 represents an NHR 'or NHOR radical "in which R 'or R" identical or different represent a hydrogen atom, a linear, branched or cyclic alkyl, alkenyl or alkynyl radical containing up to 8 carbon atoms, an aryl radical containing up to 14 carbon atoms optionally substituted , R5 represents a hydrogen atom or an O-alkyl radical containing up to 8 carbon atoms, Re an alkyl or CH2-0-alkyl radical, in which alkyl represents an adical alkyl containing up to 8 carbon atoms, R7 represents a hydrogen atom or an alkyl radical containing up to 8 carbon atoms or R6 and R7 form together with the carbon which carries them, a cycle, as well as their salts addition with the bases. As examples of bases, mention may be made of salts formed with amines such as arginine, lysine, Na +, K +, NH3 +, N (alk) 3+ alc3 ions which represent an alkyl radical containing up to 8 carbon atoms. In the definition of the substituents: the alkyl, alkenyl or alkynyl radical is preferably a methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tertbutyl, decyl or dodecyl, vinyl, allyl, ethynyl, propynyl, cyclobutyl, cyclopentyl radical or cyclohexyl, the halogen is preferably fluorine or chlorine, or bromine, - the aryl radical is preferably the phenyl radical. The subject of the invention is, more particularly, the compounds of the formula (I) in which Ri represents an alkyl radical containing up to 4 carbon atoms, for example a radical the compounds of the formula (I) in which Ri represents a benzoyl radical, the compounds of the formula (I) in which R 2 represents a hydrogen atom, the compounds of the formula (I) in which R 3 represents a radical methyl, the compounds of the formula (I) in which R 5 is an OCH 3 radical, the compounds of the formula (I) in which Re and R 7 represent a methyl radical or an ethyl radical as well as those in which R 6 and 7 they form, with the carbons which carry them, a cyclopentyl radical. Among the preferred compounds of the invention, mention may be made of the compounds of the formula (I) in which R4 represents a radical NH-0-CH2-C = CH. The subject of the invention is very particularly the compounds of which the preparation is given later in the experimental part and very particularly the product of examples 10 and 11. The products of the general formula (I) possess a very good antibiotic activity on gram® anaerobic bacteria such as staphylococci, streptococci, pneumococci, enterococci, listeria. The compounds of the invention can be used as medicaments in the treatment of infections of sensitive germs and, mainly, in those of the staphylococcus, such as septicemia of staphylococcus, malignant staphylococcus of the face or skin, pyodermitis, septic or suppurative ulcers, boils, anthrax, phlegmon, erysipelas and acne, staphylococcal such as acute or post-acute anginas. , bronchopneumonia, pulmonary suppurations, streptococities such as acute angina, otitis, sinusitis, scarlet fever, pneumococcal pneumonia, bronchitis and diphtheria. The products of the present invention are also active against infections due to germs such as Haemophilus influenzae. The subject of the invention is the compounds of the formula (I) as well as their pharmaceutically acceptable salts as medicaments. The invention relates more particularly to the compounds mentioned above as preferred compounds as medicaments. The subject of the invention is also pharmaceutical compositions containing as an active ingredient at least one of the drugs defined above.

These compositions can be administered orally, rectally, parenterally or locally via topical application on the skin and mucous membranes, but the preferred route of administration is the buccal or injectable route. They are solid or liquid and are presented under the pharmaceutical forms commonly used in human medicine, such as, for example, plain or dragee-shaped tablets, capsules, granules, suppositories, injectable preparations, ointments, creams , the gels; they are prepared according to the usual methods. The active ingredient (s) can be incorporated in the excipients usually used in these pharmaceutical compositions, such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fatty substances of animal or vegetable origin, paraffin derivatives, glycols, various wetting agents, dispersants or emulsifiers, preservatives. These compositions may also be presented in the form of a powder intended to be dissolved extemporaneously in a suitable vehicle, for example in sterile pyrogen-free water.

The dose administered varies depending on the condition treated, the subject in question, the route of administration and the product considered. It can be understood, by example, between 50 mg and 3000 mg per day orally or injectable, in the adult for the preferred products.

The subject of the invention is a process for Preparation of the compounds of the formula (I) characterized by submitting a compound of the formula (II): Or to the action of a compound of the formula R, -C -Hal in the which Ri retains its previous meaning and Hal represents a halogen atom to obtain the compound of the formula (III): which is subjected to the action of a compound of the formula R 4 H (IV) to obtain the compound of the formula The invention also has as new chemicals, the compounds of formula (II) and (III). In a preferred embodiment, Hal is a chlorine atom. The compounds of the formula (II) used as starting materials of the process of the invention can be prepared as indicated below in the experimental part. The preparation of the compounds of the formula (II) described in the experimental part can be schematized as follows: Another subject of the invention is a process characterized in that a compound of the formula (V) is subjected to: in which the substituents retain their previous meaning and OM represents a blocked hydroxyl radical, with the action of a compound of the formula RiCOHal in which Ri retains its previous meaning and Hal represents a halogen atom, then with the action of an agent of OH function release to obtain the corresponding compound of formula (I): The products of the formula (V) used as starting products are new products and are themselves an object of the invention.

The compounds of the formula (V) can be prepared according to the procedure indicated in the experimental part. The experimental part can be schematized as follows.

Preparation 1: 4, 7-dihydroxy-8-methyl-3- (phenylazo) -2H-1-benzopyran-2-one Stage A: C5H5 N + = N, Cl "10.62 g of aniline are introduced at 10 ° C. 138 ml of a 36% hydrochloric acid solution, a solution containing 23.32 g of sodium nitrite and 123 ml of water is added, maintaining the temperature between 0 and 5 ° C. A solution is obtained that is maintained at 5 ° C for 45 minutes, a product is obtained which is used as follows: Step B: 4, 7-dihydroxy-8-methyl-3- (phenylazo) -2H-1-benzopyran-2-one 33.75 g of 4 are introduced, 7-Dihydro-8-methyl-2H-l-benzo-pyran-2-one in 1,1,1 ethanol, 138.3 g of sodium acetate are added and 150 ml of product prepared in step A are added. keep the reaction mixture under stirring for 30 minutes and add 460 ml of water, keep stirring for 1 hour, rinse the product obtained with water or methyl cyanide and with ether, dry and obtain 87.34 g of product. searched.

Preparation 2: 2, 3-cyclic carbonate and 1- (2,2,2-trichloroethanimidate) of 6-deoxy-5-C-methyl-4-0-methyl-L-lixo-hexopyranose Step A: 2, 3- cyclic carbonate of 6-deoxy-5-C-methyl-4-0-methyl-L-lixo-hexopyranose 50 g of 6-deoxy-5-C-methyl-4-0-methyl-L-lixo-hexopyranose are introduced. in 2L of dichloro 1,2-ethane. 44.3 g of carbonyl diimidazole are added. It is brought to reflux for 3 H 30. It is allowed to return to room temperature. Concentrate and obtain 120 g of the product which is subjected to chromatography on silica eluting with the mixture of methylene chloride acetone 9-1. Thus, 23.19 g of the desired product are obtained. Step B: 2, 3-cyclic carbonate and 1- (2, 2, 2-trichloro-ethanimidate) of 6-deoxy-5-C-methyl-4-0-methyl-L-lixo-hexopyranose. 276 mg of cesium carbonate, 18.17 g of the product prepared in stage A and 16 ml of trichloromethane cyanide in 250 ml of methylene chloride. The reaction mixture is kept under stirring for 3 hours. It 1 add 7 ml of trichloromethane cyanide. The product obtained is maintained under stirring for 1 hour and the product obtained is eluted with the mixture of cyclohexane ethyl acetate (5-5). Thus, 27.01 g of the desired product are obtained.

EXAMPLE 1: 3'-cyclopropylcarbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-α-alpha-L-lixo-hexapyranosyl) oxy] -4 -hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -cyclopropanamide Stage A: 7- [(2,3-carbonyl-6-deoxy-5-C-methyl-4- O-methyl-. Alpha.-L-lixo-hexopyranosyl) oxy]] -4-hydroxy-8-methyl-3- (phenylazo) -2H-1-benzopyran-2-one 36.7 g of the preparation product are introduced 1 and 25 g of the product of preparation 2 in 500 ml of methylene chloride. 1.2 ml of BF3, Et20 are added. They are stirred for 20 hours at 20 ° C. 100 ml of water are added, stirred, filtered and decanted. The precipitate is washed with methylene chloride, decanted, the organic phases are washed with water, combined, dried and concentrated. 500 ml of ethyl ether are added. It is stirred for 1 hour at 20 ° C and 15 minutes at 0 ° C. It is drained, rinsed and washed with ethyl ether. The desired product is thus obtained 30 g (71%). Step B: 3-amino-7- [(2,3-carbonyl-6-deoxy-5-C-methyl-4-0-methyl-. Alpha.-L-lixo-hexopyranosyl) oxy]] -4 -hydroxy-8-methy1-2H-l-benzopyran-2-one 30 ml of water, 1.8 g of sodium acetate and 1.7 g of dithionite are added in a suspension containing 1.5 g of the product from the preceding stage and 15 ml. of ethanol. It is brought to reflux in 30 minutes. Reflux is maintained for 10 minutes. It is filtered. It is brought to 20 ° C, cooled to 0 ° C. It is dried, covered with ethyl ether, drained and dried. The desired product is thus obtained (858 mg). Step C: N- [7- [(2,3-carbonyl-6-deoxy-5-C-methyl-4-0-methyl- .alpha.-L-lixo-hexopyranosyl) oxy]] -4- hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -cyclopropanecarboxamide 20 ml of ethyl acetate are added to 1 g of the product of the preceding stage. It is crushed with the spatula. 250 mg of pyridine are added. 256 mg of cyclopropane carboxylic acid chloride are added. It is stirred for 1 hour 30 minutes at 20 ° C. It is diluted with 100 ml of ethyl acetate and 50 ml of water. It is decanted, washed with sodium hydrogen carbonate, with water, and with hydrochloric acid. Dry, filter and concentrate. The product obtained on silica is chromatographed eluting with the hexane / ethyl acetate mixture (1-1). The desired product is thus obtained. Step D: 3'-cyclopropyl-carbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-Lixo-hexopyranosyl) oxy] -4 -hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -cyclopropanamide 82 μl of cyclopropylamine and 283 μl of 1,8-diazabicyclo [5.4.0] undec-7-ene are added in a solution containing 453 mg of the product from the preceding stage and 10 ml of DMF. It is stirred for 20 hours at 20 ° C. It is poured over a diluted solution of monosodium phosphate. It is extracted with ethyl acetate, washed with water, dried, filtered and concentrated. 563 mg of the product which is subjected to chromatography eluting with the heptane / ethyl acetate 30-70 mixture are obtained. It is eluted with methanol, 312 mg of the product is obtained which is covered or coated in a mixture of ethyl acetate / methanol 8-2. It runs off. It is concentrated and 113 mg of the desired product are obtained. Rf = 0.18 heptane / ethyl acetate 30-70.

EXAMPLE 2: 3'-N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-α-alpha-L-hexyl-hexopyranosyl) -carbamic acid ester) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -cyclopropanecarboxamide 102 mg of sodium hydride are added in a suspension containing 237 mg of isopyloxyamine hydrochloride and 7.5 my DMF. Stir for 1 hour at 20 ° C. 0.25 ml of triethylamine and the product prepared in stage C of example 1 are added. It is taken 3 hours at 50 ° C, 150 mg of DMAP is added and it is kept overnight at 50 ° C. 150 mg of DMAP and 132 mg of isopyloxyamine hydrochloride are added. Stir 20 hours at 50 ° C. It is brought to 20 ° C. It is poured into a normal solution of cold hydrochloric acid, extracted with ethyl acetate, washed with water, dried, filtered and concentrated. 253 mg of the product is obtained which is subjected to chromatography on silica eluting with the heptane / ethyl acetate 3-7 mixture. 48 mg of the desired product are obtained, rf = 0.15.

EXAMPLE 3: 3'-N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-Lixo-hexopyranosyl) -carbamic acid ester) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -cyclopropane-carboxamide 1.0 ml of LiC104 solution in 3 molar Et20 is added in a suspension containing 302 mg of the product prepared in step C of example 1 and 5 ml of ethyl ether. The mixture is crushed. It is placed under ultrasound for 15 minutes. It is kept under stirring for 5 hours, 15 ml of LiC104 / Et2 solution are added. Stir 16 hours at 20 ° C, dilute with ethyl acetate and wash with water. Dry, filter and concentrate. 365 mg of the product is obtained which is subjected to chromatography on silica eluting hexane / ethyl acetate (4-6) then with a mixture of methanol / ethyl acetate 40-60. 36 mg of the desired product are obtained. By operating as above, the following products have been obtained: - N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-) -3'-ester (1-methylethoxy) -carbamic acid. alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -benzeneacetamide-3'-ethoxycarbamic acid ester of N- [ 7- [(6-deoxy-5-C-methyl-4-O-methyl-.alpha. -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran -3-yl] -benzene-acetamide-3'-ester of the (lR-trans) ethoxycarbamic acid of N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl- .alpha. L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2,2-dimethyl-3-ethenyl-cyclopropanamide-3'-acid ester cyclopropyl-carbamic acid N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-α-alpha-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2- oxo-2H-l-benzopyran-3-yl] -benzeneacetamide 3'-cyclopropyl-carbamic acid ester of N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl- .alpha. -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l- benzopyran-3-yl] -benzenepropanamide-3'-ester of (1-methylethoxy) -carbamic acid of N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl- .alpha. -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -benzenepropanamide-3'-ester of butoxycarbamic acid of N- [7- [(6-deoxy-5-C-methyl-4-O-methyl-α-alpha-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-3 -yl] -2-methyl-propanamide-3'-propoxycarbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-O-methyl-. alpha. -L-lixo -hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2-methyl-propanamide 3'-cyclopropyl-carbamic acid ester of N- [7- [ (6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3 il] -cyclobutanamide.

Preparation 3: 3-amino-7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0- [[2-propynyloxy) amino] carbonyl] -2-0- [(tetrahydro- 2H-pyran-2-yl) oxy] -. alpha. -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methy1-2H-l-benzopyran-2-one Step A: 7- [[6-deoxy-5-C-methyl-4-0-methyl- 2-0- [(tetrahydro-2 H -pyran-2-yl) oxy] -3-0 [(triethylsilyl) oxy] -. alpha. -L-lixo-hexopyran-sil] oxy] -4-hydroxy-8-methyl-2H-l-benzopyran-2-one 28.0 g of the product P prepared subsequently is subjected to hydrogenation under reduced pressure in the presence of palladium on carbon. The palladium is filtered and rinsed with THF. Concentrate under reduced pressure and obtain 32.48 g of the product which is purified on silica eluting with the mixture hexane / ethyl acetate 6-4. Step B: 7- [[6-deoxy-5-C-methyl-4-0-methyl-2-0- [(tetrahydro-2H-pyran-2-yl) oxy] -3-0- [(triethylsilyl) oxy] -. alpha.-L-lixo-hexopyran-sil] oxy] -4-hydroxy-8-methyl-3- (phenylazo) 2H-1-benzopyran-2-one An amount of 143 ml of normal acid solution hydrochloric at 0 ° C, 3.54 g of aniline are added. It is kept under stirring at 0 ° C for 15 minutes, a solution of 2.9 g of sodium nitrite in 30 cm3 of water is added. A solution of 14.39 g of sodium acetate in 150 ml of water is added. It is kept under stirring for 15 minutes, a solution containing the product of the preceding step in 150 ml of ethanol is added. It is kept under stirring for 15 minutes at 0 ° C, 300 ml of AcOEt are added. It is decanted, washed with sodium hydrogen phosphate, dried and concentrated. 34 g of the product are obtained which is purified by chromatography on silica eluting with hexane, then with the hexane / ethyl acetate mixture 60-40. 17.55 g of the product are obtained. Step C: 7- [[6-deoxy-5-C-methyl-4-0-methyl-2-0- [(tetrahydro-2H-pyran-2-yl) oxy] -. alpha -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-3- (phenylazo) -2H-l-benzopyran-2-one 57.5 ml of Bu4NF molar solution are added in THF in a solution containing the product prepared in the preceding step in 400 ml of THF. It is kept under stirring at 0 ° C for 5 hours. Wash with a saturated solution of NaH2P04, decant, concentrate and dry. 34 g of the product are obtained which is purified by chromatography on silica eluting with hexane 60 AcOEt 40. 17.55 g of the desired product are obtained. Step D: 7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0- [[(2-propynyloxy) -amino] carbonyl] -2-0- [(tetrahydro-2H- piran-2-yl) oxy] -. alpha. -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-3- (phenylazo) -2H-l-benzopyran-2-one a) It is placed in solution at 0 ° C in 250 ml of methylene chloride 17.55 g of the product of the preceding stage. 9.62 g of DMAP and 9 g of paranitrophenol chloroformate were added. It is stirred for 1 hour and 1.40 g of paranitrophenol chloroformate are added. It is concentrated under reduced pressure. b) In a second ball flask under nitrogen at 0 ° C, the propargyloxyamine hydrochloride is suspended in 250 ml of DMF. 6.7 g of sodium hydride are added. The reaction mixture is kept under stirring for 1 hour. The product prepared in stage a) to which the preceding solution is added is collected with 250 ml of DMF at 0 ° C. It is kept under stirring for 1 hour. The reaction mixture is poured into a mixture of aqueous sodium phosphate acid solution and ethyl ether. It is filtered, washed with ether and dried. 16.06 g of the desired product are obtained. Step E: 3-amino-7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0 - [[(2-propynyl-oxy) -amino] carbonyl] -2-0- [(tetrahydro-2H-pyran-2-yl) oxy] - .alpha.-L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methy1-2H-l-benzopyran-2-one dipped in a bath of oil at 85 ° C, a suspension containing 16 g of the product from the preceding stage, 22.7 g of sodium dithionite, 10.7 g of sodium acetate, 400 ml of water and 90 ml of ethyl alcohol. It is kept under agitation for 60 minutes. It is filtered. The filtrate is kept for 2 hours in an ice bath. The obtained crystals are drained and washed with water. They are dried and 10.26 g of the desired product are obtained.

Product P: 7- [[6-deoxy-5-C-methyl-4-0-methyl-2-0- (tetrahydro-2 H -pyran-2-yl) -3-0- (triethylsilyl) -.alpha. -L-lixo-hexopyranosyl] oxy] -4- (diphenylmethoxy) -8-methyl-2H-l-benzopyran-2-one Stage A: 4- (diphenylmethoxy) -8-methyl-7- (tetrahydro-2H-pyran -2-yl) -2H-l-benzopyran-2-one 55 g of 4-hydroxy-8-methyl-7- (tetrahydro-2H-pyran-2-yl) -2H-l-benzopyran-2 are introduced One in 250 ml of anhydrous dimethylformamide heated at 40 ° C was added, and a solution of 58.3 g of diphenyldiazomethane in 250 ml of DMF was added dropwise. The addition is made in 3 hours maintaining the temperature at 40 ° C. Several portions of 3 g of diphenyldiazomethane are again added and the mixture is stirred at 40 ° C for one hour. The reaction medium is poured into 2 1 of sulfuric ether. The organic solution is washed with an aqueous solution of sodium bicarbonate, with a solution of soda (0.1 M), with water and with brine. It evaporates to dryness. The residue is stirred in a mixture of isopropyl ether-hexane (1-2). The insoluble dries and dries. 20.5 g of the desired product are obtained. CCM CH2Cl2-AcOEt (95-5). Rf = 0.44 Stage B: 4- (diphenylmethoxy) -7-hydroxy-8-methyl-2H-1-benzopyran-2-one 35 ml of a solution of 0.9 M hydrochloric acid in methanol are added in a solution containing a mixture of 20 g of the product from step A, 100 ml of dichloromethane and 100 ml of methanol. The mixture is stirred at room temperature for 2 hours and the solvents are evaporated. The residue is dispersed in absolute ethanol cooled to 0 ° C. the insoluble is drained and rinsed with cold alcohol then with sulfuric ether. Dry and collect 15.53 g of the product which is dispersed in the ether, drained and dried. 14.54 g of the desired product are obtained. NMR XH MHz, CDC13, ppm) d 2.31 (s, 3H), 5.62 (s, 1H), 6.35 (s, 1H), 6.78 (d, 1H, J = Hz), 7.75 (d, 1H, J = _Hz ), 6.99 to 7.10 (m, _H), 7.30 to 7.42 (m, _H). Step C: 7- [[6-deoxy-5-C-methyl-4-0-methyl-. alpha -L-lixo-hexopyranosyl] oxy] -4- (diphenylmethoxy) -8-methyl-2H-1-benzopyran-2-one A mixture of 91.13 g of the product of stage B is cooled to 0 ° C., 58.6 g of 6-deoxy-5-C-methyl-4-0-methyl-L-lixo-hexopyranose and 80 g of triphenylphosphine in 900 ml of dichloromethane. 60 ml of diisopropylazodicarboxylate are added dropwise. It is stirred for 1 hour at room temperature. 34 g of triphenylphosphine and 25 ml of diisopropylazodicarboxylate are added. Stir 1 hour at room temperature. 34 g of triphenylphosphine and 25 ml of diisopropylazodicarboxylate are added and the mixture is stirred at room temperature for 12 hours. Concentrate under vacuum. Chromatograph eluting with a mixture of toluene / isopropyl alcohol (95-5). After the meeting of the fractions and evaporation of the solvents, they are collected after recrystallization from the isopropyl ether, 86.33 g of the desired product. NMR XH (300 MHz, CDC13, ppm) d 1.13 (s, 3H), 1.37 (s, H), 2.24 (s, 3H), 2.69 (s, 1H), 2.79 (s, 1H), 3.38 (d, 1H), J = 10 Hz), 3.60 (s, 3H), 4.24 (m, 1H), 4.28 (m, 1H), 5.56 (s, 1H), 5.64 (d, 1H, J = 1.5 Hz) , 6, (s, 1H), 7.18 (d, 1H), 7.81 (d, 1H), 7.39 (m, 10H). Step D: 7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0- (triethylsilyl) -alpha-L-lixo-hexopyranosyl] oxy] -4- (diphenylmethoxy) -8- methyl-2H-l-benzopyran-2-one 26.6 g of imidazole and 70.15 ml of diisopropylethylamine are added in a solution cooled to 0 ° C, containing 80 g of the product of the preceding step and 600 ml of dichloromethane. 33.5 ml of triethylsilyl chloride are added dropwise. Stir 1 hour at room temperature. It is washed with an aqueous solution of sodium dihydrogen phosphate, 1 M, with water and with brine. Dry over magnesium sulfate, filter and concentrate. 98.58 g of the product which is purified by chromatography on silica eluting with the dichloromethane acetone mixture (from 0.8 to 1%) are collected. 46.5 g of the product are obtained. XH NMR (300 MHz, CDCl3-d6, ppm) d 0.60 (q, _H, J = _Hz), 0.74 (q, _H, J = _Hz), 0.97 (t, _H, J = _Hz), 1.00 (t, _H, J = _Hz), 1.10 (s, 3H), 1.32 (s, 3H), 2.24 (s, 2H), 2.74 (s, 1H), 3.31 (d, 1H, J = _Hz), 3.54 (s, 3H), 4.07 (m, 1H), 4.29 (dd, 1H, J = Hz), 5.50 (s, 1H), 5.65 (d, 1H, J = Hz), 6.35 (s, 1H), 7.28 (d, 1H, J = Hz), 7.81 (d, 1H, J = Hz), 7.40 (m). Step E: 7- [[6-deoxy-5-C-methyl-4-0-methyl-2-0- (tetrahydro-2H-pyran-2-yl) -3-0- (triethylsilyl) -alpha-L -lixo-hexopyranosyl] oxy] -4- (diphenylmethoxy) -8-methyl-2H-1-benzopyran-2-one 19 ml of dihydropyran and 400 mg of APTS are added in a solution containing 67 g of the product from the stage precedent and 1 1 dichloromethane. It is stirred for 40 minutes at room temperature, 300 mg of APTS are added. After 30 minutes, 100 mg of APTS are added, then also 100 mg of APTS. It is stirred for 20 additional minutes, then the acid carbonate is introduced as finely ground sodium. It is stirred for 10 minutes, the reaction medium is diluted with a mixture of hexane / ethyl acetate (1-2), washed with water and with brine. The solvents are dried and evaporated. The product obtained is subjected to chromatography eluting with the heptane / ethyl acetate (4-1) mixture. 77.9 g of the desired product are collected.

NMR XH (300 MHz, DMSO-d6, ppm) d 0.64 (q, _H, J = _Hz), 0.73 (q, _H, J = _Hz), 0.95 to 1.32 (_H), 2.25 (s, _H), 2.27 (s, _H), 3.30 (d, _H, J = Hz), 3.4 (d, _H, J = Hz), 3.50 (m, 2H), 3.93 (m, 2H), 3.53 (s, _H), 3.54 (s, _H), 4.04 to 4.15, 4.36 (dd, _H, J = _Hz), 4.94 (1), 4.96 (1), 5.50 (if, H), 5.65 (if), 6.37 (s, 1H), 7.15 (d, _H, J = _Hz), 7.19 (d, _HH, J = Hz), 7.81 (m, 1H), 7.30 to 7.44, 1.47 to 2.00.

EXAMPLE 4: 3'-N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-lixo-hexopyranosyl) -carbamic acid ester) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -benzamide 60 μl of triethylamine and 50 μl of benzyl chloride are added in a solution containing 200 mg of the product of Preparation 3 and 4 ml of methylene chloride. Stir for 1 hour 30 at 0 ° C. The temperature is allowed to rise to 20 ° C. It is poured over a mixture of ice and monosodium phosphate. It is extracted with methylene chloride, dried, filtered and concentrated. 400 ml of methanol are added at 20 ° C, 40 mg of TsOH, H20 are added. It is stirred for 2 hours at 20 ° C. It is diluted with methylene chloride, washed with water, dried, filtered and concentrated. 90 mg of product are obtained. The aqueous phase is extracted with ethyl acetate, dried, filtered and concentrated. 75 mg of the product are obtained. The 90 mg and 75 mg of the product are combined. Chromatograph on silica eluting with methylene chloride, ethyl acetate, acetic acid 80-20-1. 105 mg of the desired product are obtained.

EXAMPLE 5: 3'-2- (6-Deoxy-6-C-methyl-4-0-methyl-α-alpha-L-mannopyranosyl) oxy] -carbamic acid ester] -4- hydroxy-3- [1- (methoxyimino) ethyl] 8-methyl-2H-l-benzopyran-3-yl] -2-one It is placed in solution at 20 ° C in 10 ml of methylene chloride, 139 mg of acid 2-methoxyiminopropanoic acid and 250 mg of pentafluorophenol. 270 mg of DCC in solution in 10 ml of methylene chloride are added. Stir 2 hours 30 minutes at 20 ° C. It is filtered, the filtered product is concentrated and redissolved in 10 ml of DMF. 20 ml of the solution thus obtained are stirred at 20 ° C under nitrogen atmosphere and 250 mg of the product of preparation 3 are added. They are stirred for 15 hours at 20 ° C. It is diluted with methylene chloride, washed with water, dried, filtered and concentrated. The residue obtained is dissolved in 5 ml of methanol at 20 ° C. 80 mg of TsOH, 1H20 are added. Stir 5 hours at 20 ° C. Purify by chromatography on silica eluting with the mixture of methylene chloride, ethyl acetate, acetic acid 80-20-1 then hexane ethyl acetate 50-50. 100 mg of the desired product are obtained, rf = 0.1.

EXAMPLE 6: N- [7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0 - [[(2-propynyloxy) amino] carbonyl] -. alpha. -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2- (2-pyridinylmethoxy) -acetamide Step A: 2- [(2 -pyridinyl) methoxy] -acetic acid. In 20 minutes at 0 ° C, 0.530 g of sodium hydride are added in a solution of 1 g of 2-hydroxymethylpyridine and DMF. 1.6 ml of ethyl chloroacetate are added at 0 ° C. 2 ml of a sodium acid phosphate solution are poured in, then concentrated under reduced pressure. The product obtained is subjected to chromatography on silica eluting with the mixture of methylene methanol chloride 90-10. 4.5 g of the product is obtained which is subjected to chromatography on silica eluting with the mixture of methylene chloride, methanol 90-10. The product obtained is purified and 1.30 g of the desired product are obtained. Step B: 2- [(pyridinyl) methoxy] acetic acid 3.7 ml of a 2 N sodium hydroxide solution are added in a solution containing 1.3 g of the product prepared in the preceding step and 10 ml of ethanol. It is kept under stirring for 1 hour, brought to pH < 7 by the addition of a normal solution of hydrochloric acid and concentrated under reduced pressure, taken up in acetone and filtered. The mother liquors are concentrated and 1.01 g of the desired product are obtained. Step C: N- [7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0 - [[(2-propynyloxy) amino] carbonyl] -. alpha. -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2- (2-pyridinylmethoxy) -acetamide It is kept under stirring for 30 minutes, 0.2 g of the product of preparation 3, 0.065 g of the product of stage B, 0.053 g of HOBT and 0.075 g of EDCS and 6 ml of methylene chloride. It is concentrated to dryness, a product is obtained which is chromatographed on silica eluent 90-10 methylene methanol chloride. 148 mg of the product that is collected in the methanol are obtained, 40 mg of APTS are added. The product obtained is subjected to chromatography eluting with the mixture of methylene chloride-methanol 90-10. 0.110 g of the desired product are obtained.

EXAMPLE 7: 3 '- (2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-O-methyl-alpha-L-lixo-hexopyranosyl)] oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2 - [(1, 2, 5-thiadiazol-3-yl) oxy] -acetamide Stage A: acid 2- [1, 2, 5-thiadiazol-3-yl) oxy] -acetic 5.93 ml of a 2 N solution of soda are added in a solution containing 1 g of ethyl ester of 2- [1, 2, 5] -thiadiazol-3-yl) oxy] -acetic acid and 5 ml of ethanol. It is kept under stirring for 2 hours. It is brought to pH5-6 by the addition of a normal solution of hydrochloric acid. It is concentrated and 1.054 g of the product are obtained. Chromatograph on silica eluting with the mixture of methylene methanol chloride 90-10. Step B: 3 '- (2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-. Alpha. -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2- [(1,2,5-thiadiazol-3-yl) oxy] -acetamide It is poured at 0 ° C, 0.105 g of the product of the preceding step in 10 ml of methylene chloride. 2 drops of DMF are added and 0.126 ml of oxalyl chloride are added. They are kept under agitation for 30 minutes. Concentrate under reduced pressure and collect with methylene chloride. 0.164 ml of pyridine and 0.200 g of the product of preparation 3 are added in 10 ml of methylene chloride. It is kept under stirring for 20 minutes. It is poured on a cooled solution of sodium chloride. It is extracted with methylene chloride and dried. A product is obtained which is subjected to chromatography on silica eluting with the mixture of methylene methanol chloride 90-10. 76 mg of the product which is taken up in 4 ml of methanol are obtained. 22 mg of APTS are added and kept under agitation for 30 minutes. It is concentrated under reduced pressure. The product obtained is purified by chromatography on silica eluting with the mixture of methylene chloride, 95/5 methanol. 30 mg of the desired product are obtained. By operating as above, the following products have been obtained: - N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-) (2-propynyloxy) -carbamic acid ester. alpha-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2- [(5-methyl-isothiazol-3-yl) oxy ] -acetamide -3- (2-propynyloxy) -carbamic acid ester of N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-. alpha. -L-lixo-hexopyranosyl ) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2 - [[2'-ethyl- [2, 5'-bithiazole] -4-yl) methoxy ] -acetamide -3- (2-propynyloxy) -carbamic acid ester of N- [7 - [(6-deoxy-oxy] -4-hydroxy-8-methyl-2-oxo-2H-1-benzopyran- 3-yl] -2- [(l-oxide-2-pyridinyl) methoxy] -acetamide-3'-trans (2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy)] -5-C-methyl-4-0-methyl- .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2 , 2-dimethyl-3- (2-methylpropyl) -cyclopropanecarboxamide - 3'-ester of the (lR-trans) (2-propynyloxy) -carbamic acid of N- [7- [(6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-lixo -hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2,2-dimethyl-3-ethyl-cyclopropanecarboxamide-3'-acid ester (2- propynyloxy) -carbamic acid N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-. alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2 N- [7 - [(6-deoxy-5-C-methyl) - (2-propynyloxy) -carbamic acid-2-o-benzopyran-3-yl] -2-phenoxy-acetamide-3'-ester -4-0-methyl- .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -benzamide-3'-ester of the (2-propynyloxy) -carbamic acid of N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-. alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8 -methyl-2-oxo-2H-l-benzopyran-3-yl] -2-propy1-cyclopropanecarboxamide-3'-trans (2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy) -5-C-methyl-4-0-methyl- .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3 -yl] -2- (methoxymethyl) -cyclopropanecarboxamide-3'-trans (2-propynyloxy) -carbamic acid ester of 2- (butoxymethyl) -N- [7- [(6-deoxy-5-C-methyl-4-0-methyl- .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2- oxo-2H-l-benzopyran-3-yl] -cyclopropanecarboxamide-3'-(2-propynyloxy) -carbamic acid ester of N- [7 - [(6-deoxy-5-C-methyl-4-0- methyl- .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -bencenacetamide-3'-ester (2-propynyloxy) ) -carbamic N- [7 - [(6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2- oxo-2H-l-benzopyran-3-yl] -2- (1-hydroxypropyl) -cyclopropanecarboxamide-3'-carbamate (2-propynyloxy) -carbamic acid of N- [7 - [(6-deoxy-5- C-methyl-4-0-methyl-. Alpha. -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2- [( phenyl-methoxy) methyl] -cyclopropanecarboxamide-3'-2- (propyl-2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-0-methyl- .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -4-pyridi N-Carboxamide 3 '- (2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy-5-C-methyl-4-0-methyl- 1-oxide]. alpha -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -3-pyridinecarboxamide 7- [[6-deoxy-5-C-methyl- 4-0-methyl-3-0 [[(2-propynyloxy) amino] carbonyl] -.alpha. -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-carbamate of 2-propenyl-3'-ester of (2-propynyloxy) -carbamic acid of N [7 - [(6-deoxy-5-C-methyl-4-0-methyl-.alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-1 -benzopyran-3-yl] -5-thiazolecarboxamide - N - [7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0 - [[(2-propynyloxy) amino] carbonyl] - .alpha.-L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -alpha- (hydroxymethyl) -benzeneacetamide (isomer A) N- [7- [[6-deoxy-5-C-methyl-4-0-methyl-3-0 - [[(2-propynyloxy) amino] carbonyl} -. alpha -L-lixo-hexopyranosyl] oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -alpha- (hydroxymethyl) -benzenacetamide (isomer B) N- [7- [ [6-deoxy? -5-C-met? L-4-0-met? L-. alpha -L-lixo-hexopyranosyl] oxy] -4-h? Drox? -8-met? L-2-oxo-2H-l-benzop? Ran-3-? L] -4-met? Llp? Perazmcarboxam? Da N- [7- [[6-deoxy] -5-C-met? L-4-0-met? L-3-0- [[(2-propynyloxy) to one] carbonyl] -. alpha. -L-lixo-hexopyranosyl] oxy-4-hydroxy? -8-met? L-2-oxo-2H-l-benzop? Ran-3-yl] -3-h? Drox? -2-phenoxy -propanamide (isomer A) 7- [[6-deoxy? -5-C-met? l-4-0-met? l-3-0- [[(2-propynyloxy) ammo] carbonyl] -. alpha.-L-lixo-hexopyranosiljoxi] -4-h? drox? -8-met? l-2-oxo-2H-l-benzop? ran-3? l] -3-h? drox? -2- phenoxy? -propanamide (isomer B) N- [7- [[6-deoxy? -5-C-met? l-4-0-met? l-3-0- [[(2-propynyloxy) ammo] carbonyl] -. alpha.-Ll? xo-hexopyranosyl] oxy] -4-h? drox? -8-met? l-2-oxo-2H-l-benzop? ran-3-? l] -5- methyl-4-hexenamide N- [7- [[6-deoxy? -5-C-met? l-4-0-met? l-3-0- [[(2-propynyloxy) ammo] carbonil] -. alpha -L-lixo-hexopyranosyl} ox?] -4-h? drox? -8-met? l-2-oxo-2H-l-benzop? ran -3? l] -2, 2, 2-tr? Fluoro-aceta ida Preparation 4: 6-deoxy? -5-C-et? L-6-C-met? L-4-0-met? L-2, 3-0- (1-met? L ethylidene) -L-lixohexopyranose Stage A: [4S- [4-. alpha , 5- . alpha (S *)]] -β, ß-diethyl-2, 2-dimethyl-5- (hydroxymethyl) -a-methoxy-1,3-dioxolan-4-ethanol are introduced into 250 ml of tetrahydrofuran (THF), 400 ml of 1 M ethyl magnesium bromide in solution in THF, stirred for 15 minutes, then 25.2 g of .Delta were introduced. 2-methyl-3, 4-0- (1-methyl-ethylidene) -L-arabinonic acid lactone and 126 ml of THF. Stir 1 hour 30, allowing to reach room temperature. The reaction medium is poured over 480 g of an ice-water mixture (1: 1) and stirred for 15 minutes. The aqueous phase is decanted and 80 g of sodium chloride are added thereto. The aqueous phase is re-extracted with methylene chloride. The organic phases (THF + methylene chloride) are combined, dried over sodium sulphate, filtered and then evaporated to dryness under vacuum in a 50 ° C bath. It is dried and 32.9 g of the desired product are obtained. Stage B:. Delta. -5-C-Ethyl-6-C-methyl-4-0-methyl-2, 3-0- (1-methylethylidene) -L-lixonic acid lactone They are introduced into 450 ml of methylene chloride, 450 ml of dimethylsulfoxide (DMSO), 246 ml of triethylamine (TEA) and 45.6 g of the product obtained according to stage A. 90 g of the trioxide pyridine sulfide complex are added in portions while maintaining the temperature below 30 ° C. Stirring is continued for 2 hours 30. 500 ml of ether are then introduced then the reaction medium is poured onto 500 g of ice + water (1: 1). After decanting, the aqueous phase is again extracted with 500 ml of ether. The organic phases are combined, dried over sodium sulphate, filtered and then evaporated to dryness under vacuum. 66 g of the product are obtained. It is again extracted 3 times 250 ml of ether and washed with 150 ml of water. The organic phases are again combined, dried over sodium sulfate, filtered and then evaporated to dryness under vacuum. 39 g of the desired product are obtained. Step C: 6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-2, 3-0- (1-methyl ethylidene) -L-lixohexopyranose It is introduced into 390 ml of tetrahydrofuran (THF) ) 39 g of the product of the preceding stage. The reaction medium is cooled to 0 ° C, then it is introduced maintaining the temperature at 0 ° C, 120 ml of a 1.5 M solution of DIBAH in the toluene. Stir 1 hour 30 allowing the temperature to rise. It is poured on the reaction medium maintaining the temperature below 20 ° C, 500 ml of a 1 M aqueous solution of double cake of sodium and potassium. Stir one hour at room temperature. After decanting, the aqueous phase is extracted again with methylene chloride. The organic phases are combined (THF + methylene chloride), dried over magnesium sulfate, filtered and then evaporated to dryness. 38.46 g of the desired product are obtained. Step D: 6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-L-lixohexopyranose. 67.7 g of the product of the preceding step, 183 ml of 0.1 sulfuric acid are introduced into 183 ml of water. N. It is heated at 70 ° C for 2 hours 30. It is allowed to return to room temperature, then barium carbonate is added to bring the pH to around 7-8. The medium is filtered. Rinse with 60 ml of water. The filtrate is concentrated under vacuum at 45 ° C. The residue is taken up in 50 ml of ethyl acetate, then evaporated to dryness under vacuum. The operation is renewed three times with 50 ml of AcOEt. The oil obtained is dissolved in 50 ml of methylene chloride. It is filtered again. After evaporation of the methylene chloride, 55.87 g of the product are obtained. It is recovered with 80 ml of ether and stirred 3 hours at room temperature. It is drained, rinsed with a minimum of ether then dried in the oven under vacuum at 45 ° C. 28.32 g of the desired product F = 100 ° C are obtained.

EXAMPLE 8: N- [7- [[6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-3-0- [(5-methyl-lH-pyrrol-5-yl)] carbonyl) -.alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2-methyl-propanamide Step A: 2, 3-cyclic carbonate of 6-deoxy-5-C-ethyl-6-C-methyl-4-O-methyl-L-lixohexopyranose A mixture of 3,083 g of 6-deoxy-5 is cooled to 0 ° C. C-ethyl-6-C-methyl-4-0-methyl-L-lixohexopyranose and 50 ml of methylene chloride. 3.4 g of 1,1-carbonyldiimidazole and 0.168 ml of 1,8-diazo-bicyclo [5-4-0] -undec-7-ene are added. It is poured into 30 ml of a 1M sodium hydrogen phosphate solution and extracted with methylene chloride. The organic phases are washed with water, dried, filtered and concentrated. 4.09 g of the desired crude product used is obtained as in the next step. Stage B: 2, 3-cyclic carbonate and 1- (2, 2, 2-trichloroethanimidate) of 6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-L-lixo-hexopyranoside 3.05 g of trichloroacetonitrile in a mixture of 78 mg of cesium carbonate, 20 ml of methylene chloride and 3.97 g of the product from stage A are stirred for 16 hours at room temperature. It is filtered and concentrated. 5.29 g of the desired product are obtained. Step C: 7- [(2,3-carbonyl-6-deoxy-5-C-ethyl-6-C-met i 1-4-O-methyl-.alpha. -L-lixo-hexopyranosyl) oxy ] -4-Hydroxy-8-methyl-3- (phenylazo) -2H-l-benzopyran-2-one 0.13 ml of boron trifluoride etherate [BF3 (0et) 2] are introduced into a mixture containing 90 ml of methylene chloride, 3.10 g of 4,7-dihydroxy-8-methyl-3- (phenylazo) -2H-1-benzopyran-2-one and 4.7 g of the product of the preceding step. It is filtered and concentrated. 7.05 g of a product is obtained which is purified by flash chromatography on silica eluting with the mixture of methylene chloride isopropanol 95-5. A product is obtained which is crystallized from the ether, drained and dried under reduced pressure. 2.32 g of the desired product are thus obtained. Step D: 3-amino-7- [(2,3-carbonyl-6-deoxy-5-C-ethyl-6-C-methyl-4-O-methyl-. Alpha. -L-lixo-hexopyranosyl ) oxy] - -hydroxy-8-methyl-2H-l-benzopyran-2-one A mixture of 2.32 g of the product of stage C 200 ml of ethanol is placed under hydrogen pressure (approximately 1400 mbar) for 2 hours. and 232 mg of palladium on carbon at 10%. It is filtered, washed with an ethanol-methylene chloride mixture and concentrated in the rotovap under reduced pressure. 1.54 g of the product are obtained. Step E: N- [7- [(2,3-carbonyl-6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-. Alpha. -L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2-methyl-propanamide 0.55 ml of pyridine and 0.4 ml of isobutyryl chloride are introduced in a mixture of 1.5 g of the product of the preceding stage and 30 ml of methylene chloride. It is kept under agitation for one hour. Pour into 20 ml of a 1M sodium hydrogen phosphate solution, extract with methylene chloride. The organic phases are washed, dried, filtered and concentrated. 1.8 g of the desired product is obtained. Step F: N- [7- [(6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-.alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8 -methyl-2-oxo-2H-l-benzopyran-3-yl] -2-methyl-propanamide A solution containing 303 mg of the product from the preceding step, 5 ml of methanol and 1.4 ml of a solution is stirred for 2 hours. aqueous solution of sodium hydroxide at 0.5 N. 50 ml of an aqueous solution of 1 M sodium hydrogen phosphate is poured, extracted with methylene chloride. It is washed with water, dried, filtered and concentrated. 270 mg of the desired product are obtained.

Step G: N- [7- [[6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-3-0- [(5-methyl-lH-pyrrol-5-yl)] carbonyl) - .alpha.-L-lixo-hexopyranosyl) oxy] -4-hydroxy-8-methyl-2-oxo-2H-l-benzo? iran-3-yl] -2-methyl-propanamide. hours at room temperature 260 mg of the product of the preceding step, 4 ml of dimethylformamide, 0.168 ml of (1,8-diaza-bicyclo [5-4-0] -undec-7-ene) and 152 mg of 5-methyl-2-pyrrolcarboxylate of 2-2-2-trichloroethyl. Pour into 20 ml of an aqueous solution of 1M sodium hydrogen phosphate, extract with ethyl acetate. The organic phases are collected, dried, filtered and concentrated. 260 mg of the crude target product is obtained which is purified by chromatography on silica eluting with the mixture of methylene methanol chloride 95-5. Samples of 110 mg of this product are taken and 27 microliters of 1, 8-dia'za-bicyclo [5.4.0] -undec-7-ene and 3 ml of methylene chloride are added. It is stirred for 1 hour at room temperature. It is poured into 3 ml of an aqueous solution of 1M sodium hydrogen phosphate. It is extracted with methylene chloride. The organic phases are washed with water, collected and dried over magnesium sulfate, filtered and concentrated. 100 mg of the desired product are obtained.

F = 140-142 ° C.

EXAMPLE 9: 3 '- (2-propynyloxy) -carbamic acid ester of N- [7- [(6-deoxy-5-C-ethyl-6-C-methyl-4-0-methyl-α-alpha.- L-lixo-hexopyranosyl) -oxi] -4-hydroxy-8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2-methyl-propanamide. Agitate for 50 hours at room temperature 303 mg of the product prepared against the last stage of the preceding example, 3 ml of pyridine, 60 mg of lithium perchlorate and 610 mg of O-propargyl hydroxylamine hydrochloride. It is kept 3 days in the freezer and stirred again for 4 hours. It is poured into 10 ml of water and extracted with methylene chloride. The organic phases are washed, dried over magnesium sulfate, filtered and concentrated. 420 mg of the product is obtained which is purified by chromatography on silica (eluent methylene chloride-methanol 95-5). 170 mg of a regioisomer product 3/2 are obtained in mixture 75-25.

Preparation 5: [7R- (7. alpha, 8.beta., 9.beta., 10. alpha.)] -4-hydroxy) -7- [[10-methoxy-8- [(tetrahydro-2H- piran-2-yl) oxy] -9- [(triethylsilyl) -oxy] -6-oxa-spiro [4.5] decan-7-yl) oxy] -8-methyl-2H-l-benzopyran-2-one Step A: [4S- [4.alfa. , 5. alpha. (S *)]] -2, 2-dimethyl-5- [(1-hydroxycyclopentyl) methoxymethyl] -1,3-dioxolan-4-methanol 20 ml of a solution of dibromobutane (106 ml of dibromobutane in 200 ml) are introduced. of THF), in a mixture containing 43 g of magnesium, 100 ml of THF and a crystal of iodine. The reaction mixture is placed under ultrasound. 1.7 1 of THF are added. The rest of the dibromo solution is added. Stirring is maintained for 2 hours 30. A solution containing 80.37 g of 2-0-methyl-3,4- (1-methylethylidene) -L-arabinic acid delta-lactone and 1 liter of THF. Stir 4.5 hours at room temperature. Cool to 0 ° C, add a saturated solution of ammonium chloride. Decant, remove the organic phase, extract with a solution of ethyl acetate at 20% heptane. It is washed, dried, and evaporated to dryness. 111.85 g of the desired product are obtained. Step B: [3 'As- (3' a. Alpha, 7 '.alpha, 7' a.beta.)] -7 '-methoxy-dihydro-spiro [cyclopentan-1, 6'- [6H] - 1, 3-dioxolo [4,5-c] pyran] -4 '(3aH) -one 221 g of PyS03 are added in a solution containing 111 g of the product prepared in step A and a mixture of one liter of chloride of methylene, 1 liter of DMSO, 0.607 1 of triethylamine. Stir 2 hours at room temperature. They are poured over an aqueous solution of sodium acid phosphate, se. extracted with a mixture of ethyl acetate, heptane (1-1). It dries, filters and evaporates to dryness. 57.7 g of the desired product are obtained. Step C: [8R- (8.alpha., 9. alpha, 10.beta)] -10-methoxy-6-oxaespiro [4.5] -decano-7, 8, 9-triol It is added at -5 ° C, 157 ml of a 1.5 M solution of dibutylaluminum hydride in toluene in a solution containing 56 g of the product of the preceding step and 300 ml of THF. Stir at 3 ° C for 1 hour. 1 liter of a 1 M solution of double sodium tartrate and potassium is added. Stir 15 minutes at room temperature. The reaction medium is extracted with a mixture of ethyl acetate-heptane 1-1. It is washed with water, brine, dried and evaporated to dryness. The residue obtained is stirred at 70 ° C in the presence of 150 ml of a 0.1 N sulfuric acid solution and 150 ml of water for 2.5 hours. It is cooled to room temperature. It is filtered, and evaporated to dryness. 49 g of the desired product are obtained. Stage D: [7R- (7. alpha, 8.beta., 9.beta., 10. alpha.)] -7- [(8,9-dihydroxy-10-methoxy-6-oxaespiro [4.5] - decan-7-yl) oxy] -4- (diphenylmethoxy) -8-methyl-2H-1-benzopyran-2-one. 45.30 g of DIAD are added dropwise at 0 ° C in a mixture of 49 g of the product of the Preparation 3, 73 g of 4- (diphenylmethoxy) -7-hydroxy-8-methyl-2H-1-benzopyran-2-one prepared as indicated in Preparation 6 and 59 g of triphenylphosphine. Stir 1.5 hours at room temperature. One equivalent of triphenylphosphine and DIAD is added at 0 ° C. The solvents are evaporated, recovered with ether and the desired product is obtained. Stage E: [7R- (7.alpha., 8.beta., 9.beta., 10. alpha.)] -4- (diphenyl-methoxy) -7- [[8-hydroxy-10-methoxy-9] - [(triethylsilyl) oxy] -6-oxaespiro [4.5] -decan-7-yl) oxy] -8-methyl-2H-l-benzopyran-2-one 15.21 g of triethylsilane chloride are added at 0 ° C. in a solution containing 48 g of the product of the preceding step and 400 ml of methylene chloride. It is stirred for one hour at 0 ° C, washed with a 1M solution of sodium acid phosphate and rinsed with water. It dries. The product obtained is chromatographed on silica eluting with the mixture of methylene chloride acetone 99-1 and then with the mixture of toluene tert-butyl methyl ether. 28.37 g of the desired product are obtained. Stage F: [7R- (7. alpha, 8.beta., 9.beta., 10. alpha.)] -4- (diphenylmethoxy) -7- [[10-methoxy-8- [(tetrahydro -2H-pyran-2-yl) oxy] -9- [(triethylsilyl) oxy] -6-oxaespiro [4.5] -decan-7-yl) oxy] -8-methyl-2H-l-benzopyran-2-one 7.57 ml of 2, 3-dihydropyran and 400 mg of paratoluene sulphonic acid are added in a solution containing 28.1 g of the product from the preceding step and 250 ml of dichloromethane. Stir 1 hour at room temperature. Bicarbonate of soda is added and stirred for 20 minutes at room temperature. It is washed with water, the organic phases are dried over sodium sulphate. The product obtained is subjected to chromatography on silica eluting with the heptane-ethyl acetate 4.1 mixture. 16.81 g of the desired product are obtained. Stage G: [7R- (7. alpha, 8. beta, 9. beta, 10.alpha.)] -4-hydroxy) -7- [[10-methoxy-8- [(tetrahydro-2H- piran-2-yl) oxy] -9- [(triethylsilyl) -oxy) -6-oxa-spiro [4.5] -decan-7-yl) oxy] -8-methyl-2H-l-benzopyran-2-one Is stirred under a hydrogen atmosphere, a solution of 16.19 g of the product of the preceding step, 150 ml of THF, in the presence of 810 mg of palladium on carbon. It is filtered and 15.1 g of the desired product are obtained.

Preparation 6: 4- (Diphenylmethoxy) -7-hydroxy-8-methyl-2H-l-benzopi-an-2-one Step A: 4- (diphenylmethoxy) -8-methyl-7- (tetrahydro-2H-pyran-2 -yl) -2H-1-benzopyran-2-one 55 g of 4-hydroxy-8-methyl-7- (tetrahydro-2H-pyran-2-yl) -2H-1-benzopyran-2-one are introduced in 250 ml of anhydrous dimethylformamide heated at 40 ° C, and a solution of 58.3 g of diphenyldiazomethane in 250 ml of DMF is added dropwise. The addition is made in 3 hours maintaining the temperature at 40 ° C. Several portions of 3 g of diphenyldiazomethane are again added and the mixture is stirred at 40 ° C for one hour. The reaction medium is poured onto 2 1 of sulfuric ether. The organic solution is washed with an aqueous solution of sodium bicarbonate, with a solution of soda (0.1 M), with water and with brine. It evaporates to dryness. The residue is stirred in a mixture of isopropyl ether-hexane (1-2). The insoluble product dries and dries. 20.5 g of the desired product are obtained. CCM CH2Cl2-AcOEt 59565 °. Rf = 0.44. Step B: 4- (diphenylmethoxy) -7-hydroxy-8-methyl-2H-1-benzopyran-2-one 35 ml of a 0.9 M hydrochloric acid solution are added to the methanol in a solution containing a mixture of 20 g of the product from step A, 100 ml of dichloromethane and 100 ml of methanol. The mixture is stirred at room temperature for 2 hours and the solvents are evaporated. The residue is dispersed in absolute ethanol cooled to 0 ° C. The insoluble product is drained and rinsed with cold alcohol then with sulfuric ether. Dry and collect 15.53 g of the product which is dispersed in the ether, drained and dried. 14.54 g of the desired product are obtained. 1 H NMR (300 MHz, CDC13, ppm) d 2.31 (s, 3 H), 5.62 (s, 1 H), 6.35 (s, 1 H), 6.78 (d, 1 H, J = _Hz), 7.75 (d, 1 H, J = _Hz), 6.99 to 7.10 (m, _H), 7.30 to 7.42 (m, _H). EXAMPLE 10: [7R- (7.a., 8.β, 9.β, 10.a)] - (2-propynyloxy) -carbamic acid 8-hydroxy-7- [4-hydroxy-8-methyl-2] -oxo-3- (benzoylamino) -2H-l-benzopyran-7-yl) -10-methoxy-6-oxaespiro [4.5] decan-9-yl Stage A: [7R- (7.a., 8.β , 9.β, 10.a)] -4-hydroxy-7- [[10-methoxy-9 - [(triethylsilyl) oxy] -6-oxaespiro [4.5] decan-7-yl] oxy] -8-methyl -3- (phenylazo) -2H-l-benzopyran-2-one To the aqueous hydrochloric acid solution (27 ml) cooled to 0 ° C, the aniline (1.44 ml) is added dropwise. This mixture is stirred at 0 ° C for five minutes. The aqueous solution of sodium nitrite (1.18 g: in solution in 10 ml of water) is then introduced dropwise. After 20 minutes of stirring at 0 ° C, the sodium acetate (8.41 g) is added and stirred for 10 additional minutes. Ethanol (30 ml) is then added. Always at 0 ° C, a solution of [7R- (1 .a., 8.β, 9.β, 10.a)] -4-hydroxy-7- [[10-methoxy-8- [(Tetrahydro-2H-pyran-2-yl) oxy] -9- [(triethylsilyl) oxy] -6-oxaspiro [4.5] decan-7-yl] oxy] -8-methyl-2H-l-benzopyran-2 -one of preparation 5, 13.15 mmoles in 30 ml of THF. This mixture is stirred forty minutes at 0 ° C. The reaction solution is poured onto an aqueous solution of sodium dihydrogen phosphate (1M: 100 ml). Extract with an AcOEt-heptane mixture (1: 1). The organic solution is washed with water, then dried over sodium sulfate, filtered and concentrated to dryness. The desired product is thus obtained. Step B: [7R- (7.a., 8.β, 9.β, 10.a)] -7- [(8,9-dihydro-10-methoxy-6-oxaespiro [4.5] decan-7- il] oxy] -4-hydroxy-8-methyl-3- (phenylazo) -2H-l-benzopyran-2-one To a solution, cooled to 0 ° C, of the preceding product in anhydrous tetrahydrofuran (170 ml) is added drip a solution of tetrabutylammonium fluoride (1M in THF, 20 ml), allow the temperature to rise and stir for 1 hour at this room temperature, add tetrabutylammonium fluoride (1M in THF): 20 ml. and it is stirred for an additional hour. The reaction solution is poured onto an aqueous solution of sodium dihydrogen phosphate (100 ml). Extract with an AcOEt-heptane mixture (80-20). The organic solution is washed with water then dried over magnesium sulfate, filtered and concentrated to dryness. 9 g of the crude product are obtained which is purified by chromatography eluting with the dichloromethane-acetone mixture (94: 6). Stage C: [3 'aR- (3'a.a., 4 'a. , 7 '. , 7 'aa)] -4' - [[4-dihydro-8-methyl-3- (phenylazo) -2H-l-benzopyran-7-yl] oxy] -7 '-methoxy-tetrahydro-spiro [cyclopentan- 1, 6 '[6H-1, 3] dioxolo [4,5-c] pyran] -2' -one The mixture of the product from step B (2.42 g) and carbonyldiimidazole (1.6 g) in anhydrous tetrahydrofuran (30 ml. ) is heated to reflux. After forty-five minutes, the cooled reaction mixture is poured onto an aqueous solution of sodium hydrogen sulfate (10% sol: 20 ml) then extracted with dichloromethane. The organic phase is dried over magnesium sulfate. It is filtered and evaporated to dryness. The residue was purified by chromatography on silica, eluting with the dichloromethane-acetone mixture (95-5). 2.35 g of the desired product are obtained.

Step D: [3 'aR- (3' a .a., 4 * a., 7 'a., 7' aa)] -4 '- [[3-amino-4-hydroxy-8-methyl-2 -oxo-2H-l-benzopyran-7-yl] oxy] -7'-methoxy-tetrahydro-spiro [cyclopentan-1, 6 '[6H-1, 3] dioxolo [4,5-c] pyran] -2 The solution of the product from the preceding step in tetrahydrofuran (30 ml) is stirred vigorously at room temperature, in the presence of Pd / C (0.250 G: 10%), under a hydrogen atmosphere. About forty minutes the reaction is complete. The catalyst is removed by filtration. It evaporates to dryness. The residue is concreted in an ether-pentane mixture under ultrasound then isolated by filtration. After drying, 1.85 g of the desired product are recovered. Step E: [3 'aR- (3' aa, 4 'a., 7' a., 7 'aa)] -N- [4-hydroxy-7- [(7'-methoxy-2'-oxo- tetrahydro-spiro [cyclopentan-1, 6 '[6H-1, 3] dioxolo [4, 5-c] pyran] -4' -yl) oxy] -8-methyl-2-oxo-2H-l-benzopyran- 3-yl] -benzamide To the suspension cooled to 0 ° C of the product from the preceding step in dichloromethane (5 ml) is introduced trichlolamine (177 μl). 134 μl of benzoyl chloride is added to the syringe. The reaction solution is stirred for 1 hour at 0 ° C. Triethylamine (18 μl) and benzoyl chloride (13 μl) were added again and the reaction mixture was stirred for 1 additional hour at 0 ° C. The reaction solution is poured onto an aqueous solution of sodium dihydrogen phosphate (1M: 100 ml). Extract with an AcOEt-heptane mixture (80:20). The organic solution is washed with water then dried over magnesium sulfate, filtered and concentrated to dryness. The residue is purified by chromatography eluting with the mixture of heptane-ethyl acetate (2: 1). 420 mg of the desired product are obtained. Step F: [7R- (7.a., 8β, 9β, 10.a)] - (2-propynyloxy) -carbamic acid 8-hydroxy-7- [4-hydroxy-8-methyl-2] -oxo-3- (benzoylamino) -2H-l-benzopyran-7-yl] -10-methoxy-6-oxaespiro [4.5] decan-9-yl To a solution of the product of the preceding step in pyridine (dried on potash, 4 ml) is added successively O-propargilhidroxyminamina (822 mg) and lithium perchlorate (82 mg). The reaction medium is stirred 2.5 days at room temperature. The reaction solution is poured onto an aqueous solution of sodium hydrogen sulfate (at 10%: 100 ml). Extract with a mixture of AcOEt-heptane (80-20). The organic solution is washed with water then dried over magnesium sulfate, filtered and concentrated to dryness. 497 mg of the crude or unmixed desired product are obtained which is chromatographed on silica eluting with the dichloromethane-methanol (94: 6) mixture. 263 mg of the desired product are obtained. EXAMPLE 11: [7R- (7.a., 8β., 9β., 10.a)] - (2-propynyloxy) -carbamic acid 7- [4-hydroxy-8-methyl-3- [(2-methyl) -l-oxo-propyl) amino] -2-oxo-2H-l-benzopyran-7-yl] -10-methoxy-6-oxa-spiro [4.5] decan-9-yl Stage A: [3 • aR- (3 'aa ^' a. ^ 'a. ^' aa)] -N- [4-hydroxy-7- [(7 * -methoxy-2'-oxo-tetrahydro-spiro [cyclopentan-1, 6 '[6H- 1, 3] dioxolo [4, 5-c] pyran] -4 * -yl) oxy] -8-methyl-2-oxo-2H-l-benzopyran-3-yl] -2-methyl-propanamide It is subjected to hydrogenation for 2 hours under an atmosphere of H2 in the presence of palladium on carbon a solution of 810 mg of the product from step C of the preceding example namely [3 'aR- (3' aa, 4 'a., 7' a ., 7 'aa)] -4' - [[4-hydroxy-8-methyl-3-phenylazo) -2-oxo-2H-l-benzopyran-7-yl] oxy] -7'-methoxy-tetrahydro- spiro [cyclopentan-1, 6 '[6H-1, 3] dioxolo- [4,5- c] pyran] -2' -one to obtain the corresponding 3-amino product. It is filtered, rinsed with THF and the solvent is evaporated. 10 ml of methylene chloride, 240 ml of triethylamine plus 165 ml of isopropyl chloride were added at 0 ° C. Stir 1 hour at 0 ° C, diluting with methylene chloride and wash with sodium hydrogen phosphate. Chromatograph on silica eluting with the hexane / ethyl acetate 2-1 mixture and obtain 680 mg of the desired product. Step B: [7R- (7.a., 8β., 9β., 10.a)] - (2-propynyloxy) -carbamic acid 7- [4-hydroxy-8-methyl-3- [(2-methyl) -l-oxo-propyl) amino] -2-oxo-2H-l-benzopyran-7-yl] -10-methoxy-6-oxaespiro [4.5] decan-9-yl It is stirred at room temperature for 2 days and medium, a solution containing 680 mg of the product of the preceding step, 1.4 g of o-propargyl hydroxylamine and 139 mg of lithium perchlorate and 6 ml of pyridine. The reaction solution is poured onto an aqueous solution of 10% sodium hydrogen sulfate and extracted with a mixture of hexane-ethyl acetate 1-1. The organic phase is dried, the solvents are evaporated. The product obtained is subjected to chromatography on silica eluting with the mixture of methylene chloride / ethyl acetate / acetic acid 80-20-1 and 310 mg of the desired product are obtained.

EXAMPLES OF PHARMACEUTICAL COMPOSITIONS The tablets containing: Product of example 10 150 mg Excipient c.s.p. 1 g Detail of the excipient: starch, talcum, magnesium stearate Product of example 11 150 mg Excipient c.s. 1 g Detail of the excipient: starch, talcum, magnesium stearate. Injectable solutions have also been prepared from the salified products.

PHARMACOLOGICAL STUDY OF THE PRODUCTS OF THE INVENTION A - Method of dissolutions in liquid medium A series of tubes has been prepared in which a same amount of the sterile nutritive medium is distributed. The increasing amounts of the product to be studied are distributed in each tube, then each tube is seeded with a bacterial strain. After the incubation of 24 hours in the oven at 37 ° C, the inhibition of the increase is appreciated by transillumination of what allows to determine the minimum inhibitory concentrations (C.M.I.) expressed in mocrograms / cm3.

In vitro activity CM1 in μg / ml On the following strains: EXAMPLE 10 EXAMPLE 11 Staph. aureus 011HT18 < 0.04 < 0.04 Staph. epidermidis 0126042 < 0.04 < 0.04 Staph. Coag. 012HT5 0.08 0.15 Negative Strepto. Pyogene 02A1UC1 0.16 0.08 Strepto pneumoniae 030BI2 < 0.04 < 0.04 Integer Faecium 02D3IP2 0.63 0.32 Integer Faecalis 02D2UC5 1.2 0.63 The products of the examples and in particular the products of examples 10 and 11 show excellent activity. B - Inhibition of gyrase B The products are inhibitors of gyrase B; the 50% dose of the DNA overcoiling is less than 5 μg / ml. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (20)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. The compounds of the formula (I): characterized in that Ri represents an alkyl, alkenyl or alkynyl, 0-alkyl, O-alkenyl or linear, branched or cyclic O-alkynyl containing up to 8 carbon atoms optionally substituted by one or more halogen atoms, optionally interrupted by an atom of oxygen, sulfur or nitrogen, an aryl or aralkyl radical containing up to 18 optionally substituted carbon atoms, an aromatic or non-aromatic heterocyclic radical, optionally substituted mono or polycyclic, a radical NH2, NHalcí or NHalc2, NHalc3 or NHOalc, alky , alc2, alc3 and alc4 representing an alkyl radical containing up to 8 carbon atoms, R2 represents a hydrogen atom or a halogen atom, R3 represents a hydrogen atom, an alkyl radical containing up to 8 carbon atoms or a halogen atom,
2. R represents a radical NHR 'or NHOR "in which R' or R" identical or different represent a hydrogen atom, a linear, branched or cyclic alkyl, alkenyl or alkynyl radical containing up to 8 carbon atoms, an aryl radical which contains up to 14 optionally substituted carbon atoms, R5 represents a hydrogen atom or an O-alkyl radical containing up to 8 carbon atoms, Re an alkyl or CH2-0-alkyl radical, in which alkyl represents an alkyl radical containing up to 8 carbon atoms, R7 represents a hydrogen atom or an alkyl radical containing up to 8 carbon atoms or R6 and R7 form together with the carbon which carries them, a cycle, as well as their addition salts with the bases . 2. The compounds of the formula (I) defined in claim 1, characterized in that Ri represents an alkyl radical containing up to 4 carbon atoms.
3. 3. The compounds of the formula (I) defined in claim 2, characterized in that R represents a radical:
4. 4. The compounds of the formula (I) defined in claim 1, characterized in that Ri represents a benzoyl radical.
5. 5. The compounds of the formula (I) defined in any of claims 1 to 4, characterized in that R2 represents a hydrogen atom.
6. 6. The compounds of the formula (I) defined in one of claims 1 to 5, characterized in that R3 represents a methyl radical.
7. 7. The compounds of the formula '(I) defined in one of claims 1 to 6, characterized in that Rs is an OCH3 radical.
8. 8. The compounds of the formula (I) defined in any of claims 1 to 7, characterized in that R6 and RT represent a methyl radical.
9. 9. The compounds of the formula (I) defined in any of claims 1 to 7, characterized in that R6 and R7 represent an ethyl radical.
10. 10. The compounds of the formula (I) defined in any of claims 1 to 7, characterized in that R6 and R7 form, with the carbons which carry them, a cyclopentyl radical.
11. 11. The compounds of the formula (I) defined in any of claims 1 to 7, characterized in that R represents a radical NH-0-CH2-C = CH.
12. 12. The compound of the formula (I) defined in claim 1, characterized in that it is named as follows: - [7R- (7.a., 8β, 9β, 10.a)] - (2- propynyloxy) carbamate of 8-hydroxy-7- [4-hydroxy-8-methyl-2-oxo-3- (benzoylamino) -2H-1-benzopyran-7-yl] -10-methoxy-6-oxaespiro [4.5] decan-9-ilo.
13. 13. The compound of the formula (I) defined in claim 1, characterized in that it is named as follows: - [7R- (7.a., 8β, 9β, 10.a)] - (2-propynyloxy) carbamate of 7- [4-hydroxy-8-methyl-3- [(2-methyl- l-oxo-propyl) amino] -2-oxo-2H-l-benzopyran-7-yl] -10-methoxy-6-oxa-spiro [4.5] decan-9-yl.
14. 14. The compounds of the formula (I) defined in claim 1, as well as their addition salts with the pharmaceutically acceptable acids, are characterized as medicaments.
15. 15. The compounds of the formula (I) defined in claim 12 or 13 are characterized as medicaments., as well as their addition salts with pharmaceutically acceptable acids.
16. 16. The pharmaceutical compositions characterized in that they contain as active ingredient at least one medicament defined in claim 14 or 15.
17. 17. A process for preparing the compounds of the formula (I) defined in claim 1, characterized in that a compound is subjected to of the formula (II): to the action of a compound of the formula R, -c-Hat in which Ri retains its previous meaning and Hal represents a halogen atom to obtain the compound of the formula (III): which is subjected to the action of a compound of the formula R4H (IV) to obtain the compound of the formula
18. 18. As new chemical products, the compounds of the formula (II) and (III) defined in claim 17 are characterized.
19. 19. Process variant according to claim 17, characterized in that a compound of the formula (V) is subjected to: in which the substituents retain their previous meaning and OM represents a blocked hydroxyl radical, with the action of a compound RiCOHal in which R ± retains its previous meaning and Hal represents a halogen atom, then with the action of a release agent of the OH function to obtain the corresponding compound of the formula (I):
20. 20. As new chemical products, the compounds of the formula (V) defined in claim 19 are characterized.