Anthracycline Derivatives For Treating Tumor Diseases

Abstract

The invention relates to anthracycline derivative compounds for treating tumor diseases, and related methods, compositions, and kits.

Claims

1. A compound of the formula (IX) ##STR00034##

2. A compound of the general formula (X) ##STR00035## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group.

3. A compound of the general formula (XI) ##STR00036## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group.

4. A compound of the general formula (XII) ##STR00037## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group.

5. A compound of the general formula (XIII) ##STR00038## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group.

6. A compound of the general formula (XIV) ##STR00039## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group.

7. A compound of the general formula (XV) ##STR00040## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group.

8. A process for preparing compounds of the general formula (I), characterized in that an open-chain sugar compound of the general formula (II) ##STR00041## in which R.sub.7 and R.sub.5 are the same and are each alkyl or alkylene having 2 to 3 carbon atoms; R.sub.9 and R.sub.10 are each an alkyl group having 1 to 3 carbon atoms; Y[C(O)], [C(N)OH] or [CHOH], [CHNR.sub.5R.sub.6] in both possible stereoisomeric arrangements, where R.sub.5 and R.sub.6 are either each a hydrogen atom or are one hydrogen atom and one trifluoroacetyl group (TFA); in which XO, S or NR with R=hydrogen or a C.sub.1 to C.sub.4 alkyl group; R.sub.4 is an unbranched or branched alkyl or heteroalkyl chain having a chain length of 1 to 19 elements, where a maximum of 6 heteroatoms (O, N, S) in any combination are separated from one another by at least two carbon atoms, is converted by cleaving the diol and aldehyde protecting group to give a pyranose of the general formula (III) ##STR00042## in which Y[C(O)], [C(N)OH] or [CHOH], [CHNR.sub.5R.sub.6] in both possible stereoisomeric arrangements, where R.sub.5 and R.sub.6 are either each a hydrogen atom or are one hydrogen atom and one trifluoroacetyl group (TFA); in which XO, S or NR with R=hydrogen or a C.sub.1 to C.sub.4 alkyl group; R.sub.4 is an unbranched or branched alkyl or heteroalkyl chain having a chain length of 1 to 19 elements, where a maximum of 6 heteroatoms (O, N, S) in any combination are separated from one another by at least two carbon atoms, which is subsequently protected, preferably as O-trifluoroacetyl or O-para-nitrobenzoyl, forming compounds of the general formula (IIIa) or (IIIb) ##STR00043## in which Y[C(O)], [C(N)OH] or [CHOH], [CHNR5R6] in both possible stereoisomeric arrangements, where R5 and R6 are either each a hydrogen atom or are one hydrogen atom and one trifluoroacetyl group (TFA); in which XO, S or NR with R=hydrogen or a C1 to C4 alkyl group; R4 is an unbranched or branched alkyl or heteroalkyl chain having a chain length of 1 to 19 elements, where a maximum of 6 heteroatoms (O, N, S) in any combination are separated from one another by at least two carbon atoms, and these are subsequently glycosylated with a tetracyclic aglycone of the anthracycline (AA) structure type to give a compound of the general formula IIIc ##STR00044## in which AA is a tetracyclic aglycone of the anthracycline structure type and X, Y, R.sub.3 and R.sub.4 are each as defined in formula I, but in the preferred embodiment the activated pyranoses of the general formula (IIIa) or (IIIb) are reacted in a glycosidation reaction with an anthraquinone-derived aglycone of the general formula (IV) ##STR00045## in which R.sub.1 and R.sub.2 are each as defined in formula (I), wherein a reaction activation is effected, giving compounds of the general formula (Ia) ##STR00046## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom or an NO.sub.2 group, R.sub.2 is a hydrogen atom, a hydroxyl or methoxy group, or an acyl or aroyl radical, R.sub.4 is defined as (CH.sub.2CH.sub.2O).sub.n with n=1 to 6, and in which there is a hydrogen atom or a C.sub.1 to C.sub.4 alkyl group on the terminal oxygen atom of the chain.

9. The process as claimed in claim 8, characterized in that compounds of the general formula (II) are prepared by coupling a C2 unit of the general formula (V) ##STR00047## in which R.sub.7 and R.sub.8 are each as defined in formula (II) to a protected derivative of L-threose (enantiomerically pure C4 unit) of the general formula (VI) ##STR00048## in which X, R.sub.9, R.sub.10 are each as defined in formula (II) and Z=hydrogen, or at least or more than one, preferably one or two, methyl, fluorine, chlorine, bromine or nitro groups, and the resulting addition product of the general formula (VII) ##STR00049## in which R.sub.7, R.sub.8, R.sub.9, R.sub.10 are each as defined in formula (II), and Z=hydrogen, or at least or more than one, preferably one or two, methyl, fluorine, chlorine, bromine or nitro groups, and YCHOH, is oxidized by oxidation to the ketone [YC(O)] of the general formula (VII) and then the nitrogen is introduced, preferably via an oxime [YC(N)OH] of the general formula (VII), in which the protecting group on X is subsequently detached and R.sub.4 as defined in formula (I) is introduced, wherein the introduction of an unbranched or branched alkyl or heteroalkyl chain on X is effected by substitution, preferably with the aid of a non-nucleophilic base, wherein the alkyl or heteroalkyl chain to be introduced is activated with a leaving group beforehand and the resultant oxime [YC(N)OH] of the general formula (II) is subsequently reduced with a metal hydride, forming amines [YCHNH.sub.2] of the general formula (II), which are subsequently protected, forming a sugar compound of the general formula (II) [YCHNR.sub.5R.sub.6] in which R.sub.5/R.sub.6 are different and are each as defined in formula (I).

10. A process for preparing compounds of the general formula (IV) ##STR00050## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, and R.sub.2 is hydrogen, characterized in that a tricyclic bromide of the general formula (VIII) ##STR00051## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, is reacted with a synthon of the formula (IX) ##STR00052## wherein the compound of the formula (IX) is deprotonated, and the subsequent alkylation leads to formation of an enantiomerically pure compound of the general formula (X) ##STR00053## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, which is reacted with an organometallic reagent to give a compound of the general formula (XI) ##STR00054## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, and the keto group in the compound of the general formula (XI) is reduced in a hydride reduction to a hydroxyl group and then is ketalized to give a compound of the general formula (XII) ##STR00055## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, and subsequently the protecting group in the general formula (XII) is eliminated and the hydroxyl group released is oxidized by oxidation to give an aldehyde of the general formula (XIII) ##STR00056## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, and the compound of the general formula (XIII) thus obtained is converted by oxidative dealkylation to the anthraquinone derivative of the general formula XIV ##STR00057## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, and subsequent detachment of the remaining protecting groups gives the hemiacetal of the general formula (XV) ##STR00058## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, the latter is cyclized to give the compound of the general formula (XVI) ##STR00059## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, R.sub.12 and R.sub.13 are each a hydrogen atom, or are one hydrogen atom and one hydroxyl group in any combination, and the side chain hydroxyl group is oxidized to give a compound of the general formula (XVII) ##STR00060## in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, R.sub.12 and R.sub.13 are each a hydrogen atom, or are one hydrogen atom and one hydroxyl group in any combination, and, provided that R.sub.12 and R.sub.13 are each a hydrogen atom, is then hydroxylated to give a compound of the general formula (IV) in which R.sub.1 is a hydrogen atom, a hydroxyl or methoxy group, a halogen atom, especially a fluorine, chlorine or bromine atom, or an NO.sub.2 group, and R.sub.2 is hydrogen ##STR00061##

Description

EXAMPLE 1

[0052] N-[(2S,3S,4S)-3,6-dihydroxy-2-[2-[2-[2-[2-(2-methoxy-ethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]tetrahydro-pyran-4-yl]-2,2,2-trifluoroacetamide; formula (III); R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNR.sub.5R.sub.6], R.sub.5H, R.sub.6[C(O)CF.sub.3]

[0053] To a solution of 8.9 g (17.2 mmol) of N-[2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-[2-[2-2-[2-(2-methoxy-ethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]-2,2,2-trifluoroacetamide (II) in THF/H.sub.2O (4:1) are added dropwise 43 mL (0.56 mol) of trifluoroacetic acid. Subsequently, the mixture is stirred at 60 C. for 30 min. Then the reaction mixture is emptied onto 100 mL of ice-water and 87 g (1.03 mol) of solid NaHCO.sub.3 are added until pH 6-7 is attained. The reaction mixture is subsequently filtered and extracted with 3 with 200 mL of dichloromethane each time. The combined organic phases are dried over sodium sulfate, filtered and concentrated by evaporation. The resultant oil is purified by chromatography (eluent: DCM/MeOH 100:3->100:5->10:1, v/v). 2.1 g (27%) of colorless oil are isolated. The anomeric ratio is :=76:24.

[0054] .sup.1H NMR (a), (500 MHz; CDCl.sub.3): (ppm)=7.09 (m, 1H, NH); 5.41 (m, 1H, H-1); 4.47 (m, 1H, H-3); 4.18 (m, 1H, H-5); 3.92 (m, 1H, H-4); 3.79-3.69 (m, 2H, H-6/1, H-6/2); 3.62 (m, 18H, CH.sub.2O); 3.55 (m, 2H, MeOCH.sub.2); 3.35 (s, 3H, OMe); 2.00-1.91 (m, 1H, H-2/1); 1.87-1.84 (m, 1H, H-2/2)

[0055] .sup.1H NMR (13), (500 MHz; CDCl.sub.3): (ppm)=7.29 (m, 1H, NH); 5.18 (m, 1H, H-1); 4.16-4.06 (m, 1H, H-3); 3.82 (m, 1H, H-4); 3.79-3.69 (m, 2H, H-6/1, H-6/2); 3.62 (m, 19H, CH.sub.2O, H-5); 3.55 (m, 2H, CH.sub.2O); 3.35 (s, 3H, OMe); 2.04-2.00 (m, 1H, H-2/1); 1.80-1.74 (m, 1H, H-2/2).

EXAMPLE 2

[0056] [(4S,5S,6S)-6-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]-ethoxy]ethoxy]ethoxymethyl]-5-(4-nitrobenzoyl)oxy-4-[(2,2,2-trifluoroacetyl)amino]tetrahydropyran-2-yl] 4-nitrobenzoate; formula (IIIa); R.sub.3R.sub.11[C(O)PhNO.sub.2]; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNR.sub.5R.sub.6], R.sub.5H, R.sub.6[C(O)CF.sub.3]

[0057] To a solution of 1.67 g (3.38 mmol) of N-[(3S,4S,6S)-3,6-dihydroxy-2-[2-[2-[2-[2-(2-methoxy-ethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]tetrahydro-pyran-4-yl]-2,2,2-trifluoroacetamide (II) in pyridine is cooled to 0 C. under inert gas. Subsequently, 1.75 g (9.43 mmol) of p-nitrobenzoyl chloride are added and the reaction mixture is warmed to room temperature within 12 h. The reaction is quenched with H.sub.2O and then all solvents are evaporated off. The residue is taken up in dichloromethane and washed once H.sub.2O, three times with semisaturated NaHCO.sub.3 solution and once with saturated NaCl solution, dried over sodium sulfate, filtered and concentrated by evaporation. The resulting oil is purified by chromatography (eluent: ethyl acetate/petroleum ether 1:1->3:2->2:1, v/v). 1.94 g (72%) are obtained as a white foam. The anomeric ratio is :=76:24.

[0058] .sup.1H NMR (), (200 MHz; CDCl.sub.3): (ppm)=8.30 (m, 8H, Ar); 6.88 (d, 1H, J=6.56 Hz, NH); 6.67 (m, 1H, H-1); 5.76 (m, 1H, H-4); 4.80 (m, 1H, H-5); 4.46 (m, 1H, H-3); 3.63-3.46 (m, 22H, H-6/1, H-6/2, CH.sub.2O); 3.34 (s, 3H, OMe); 2.39-2.33 (m, 2H, H-2/1, H-2/2)

[0059] .sup.1H NMR (), (200 MHz; CDCl.sub.3): (ppm)=8.28 (m, 8H, Ar); 6.90 (m, 1H, NH); 6.15 (m, 1H, H-1); 5.64 (m, 1H, H-4); 4.51 (m, 1H, H-5); 4.18 (m, 1H, H-3); 3.69-3.52 (m, 22H, H-6/1, H-6/2, CH.sub.2O); 3.34 (s, 3H, OMe); 2.44-2.17 (m, 2H, H-2/1, H-2/2).

EXAMPLE 3

[0060] [(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]-oxy]-2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-ethoxy]ethoxymethyl]-4-[(2,2,2-trifluoroacetyl)amino]-tetrahydropyran-3-yl] 4-nitrobenzoate; formula (I); R.sub.1OMe; R.sub.2H; R.sub.3[C(O)PhNO.sub.2]; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNR.sub.5R.sub.6], R.sub.5H, R.sub.6[C(O)CF.sub.3]

[0061] To a solution of 225 mg (0.28 mmol) [(4S,5S,6S)-6-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-ethoxymethyl]-5-(4-nitrobenzoyl)oxy-4-[(2,2,2-trifluoroacetyl)amino]tetrahydropyran-2-yl] 4-nitro-benzoate, (III), in 15 mL of dichloromethane and 12 mL of Et.sub.2O are added 1.1 g of 4 A molecular sieve. Under inert gas, 129 mg (0.58 mmol) of trimethylsilyl trifluoromethanesulfonate are added dropwise at 40 C. and the mixture is stirred at 0 C. for 1 h, the mixture is cooled to 20 C. and 56 mg (0.14 mmol) of (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione, (IV), dissolved in 9 mL of tetrahydrofuran, are added dropwise. Subsequently, the mixture is stirred at 10 C. to 15 C. for 6 h. Added to the reaction mixture are saturated NaHCO.sub.3 solution and dichloromethane, and the phases are separated. The aqueous phase we extracted repeatedly with dichloromethane. The combined organic phases are washed with H.sub.2O and saturated NaCl solution, dried over sodium sulfate, filtered and concentrated by evaporation. The resulting residue is purified by chromatography (eluent: DCM/MeOH 100:1->100:2->100:4, v/v). 118 mg (82%) of orange-red solid are obtained.

[0062] .sup.1H NMR (500 MHz, CDCl.sub.3): (ppm)=13.93 (s, 1H, OH-6); 13.15 (s, 1H, OH-11); 8.30-8.23 (m, 4H, Ar); 7.90 (d, 1H, J=7.55 Hz, H-1); 7.76-7.72 (m, 1H, H-2); 7.35 (d, 1H, J=8.5 Hz, H-3); 6.72 (m, 1H, NH); 5.69 (m, 1H, H-1); 5.62 (m, 1H, H-4); 5.20 (m, 1H, H-7); 4.56-4.53 (m, 1H, H-5); 4.48-4.40 (m, 1H, H-3); 4.04 (s, 3H, ArOMe); 3.68-3.45 (m, 22H, CH.sub.2O, H-6); 3.33 (s, 3H, OMe); 3.12 (m, 1H, H-10/1); 2.88 (m, 1H, H-10/2); 2.57 (m, 1H, H-8/1); 2.43 (s, 3H, H-14); 2.18-2.02 (m, 3H, H-8/2, H-2)

EXAMPLE 4

[0063] N-[(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-3-hydroxy-2-[2-[2-[2-[2-(2-methoxy-ethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl] tetrahydro-pyran-4-yl]-2,2,2-trifluoroacetamide; formula (I); R.sub.1OMe; R.sub.2R.sub.3H; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNR.sub.5R.sub.6], R.sub.5H, R.sub.6[C(O)CF.sub.3]

[0064] A solution of 99 mg (0.1 mmol) of [(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]-4-[(2,2,2-trifluoroacetyl)amino]tetrahydropyran-3-yl] 4-nitrobenzoate, (I), in 52.1 mL of methanol and 0.1 mL of dichloromethane is cooled to 0 C. Subsequently, 1.3 mL of 0.1 N NaOH are added dropwise and the mixture is stirred at 0 C. for 30 min. The reaction mixture we then neutralized with glacial acetic acid, and ethyl acetate and saturated NaCl solution are added. The phases are separated and the aqueous phase is extracted once with ethyl acetate. The combined organic phases are washed with saturated NaCl solution, dried over sodium sulfate, filtered and concentrated by evaporation. The resultant residue is purified by chromatography (eluent: DCM/MeOH 100:4, v/v). 75.9 mg (89%) of orange-red solid are obtained.

[0065] .sup.1H NMR (500 MHz, CDCl.sub.3): (ppm)=13.94 (s, 1H, OH-6); 13.23 (s, 1H, OH-11); 7.99 (d, 1H, J=7.55 Hz, H-1); 7.75 (t, 1H, J=8.02 Hz, H-2); 7.36 (d, 1H, J=8.5 Hz, H-3); 7.10 (m, 1H, NH); 5.56 (m, 1H, H-1); 5.25 (m, 1H, H-7); 4.22-4.14 (m, 1H, H-3); 4.14-4.11 (m, 1H, H-5); 4.05 (s, 3H, ArOMe); 3.98 (m, 1H, H-4); 3.87-3.71 (m, 2H, H-6/1, H-6/2); 3.69-3.53 (m, 20H, CH.sub.2O); 3.35 (s, 3H, OMe); 3.27-3.17 (m, 1H, H-10/1); 2.87-2.84 (m, 1H, H-10/2); 2.39 (s, 3H, H-14); 2.37-2.34 (m, 1H, H-8/1); 2.12-2.01 (m, 2H, H-8/2, H-2/1); 1.86-1.83 (m, 1H, H-2/2)

EXAMPLE 5

[0066] (7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-ethoxymethyl]tetrahydropyran-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione; formula (I); R.sub.1OMe; R.sub.2R.sub.3H; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNH.sub.2]

[0067] A solution of 60 mg (0.07 mmol) of N-[(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]-oxy]-3-hydroxy-2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]-ethoxy]ethoxy]ethoxymethyl]tetrahydropyran-4-yl]-2,2,2-trifluoroacetamide, (I), in 12.5 mL of 1 N NaOH is stirred at room temperature for 20 min. The reaction mixture is subsequently neutralized with 12.5 mL of 1N HCl and extracted with dichloromethane until the extracts no longer have any orange color. The combined organic phases are washed with saturated NaCl solution, dried over sodium sulfate, filtered and concentrated by evaporation. The resulting residue is purified by chromatography (eluent: DCM/MeOH 10:1->10:2, v/v). 13 mg (24%) of orange-red solid are obtained.

[0068] .sup.1H NMR (500 MHz, CDCl.sub.3): (ppm)=13.81 (s, 1H, OH-6); 13.12 (s, 1H, OH-11); 7.85 (d, 1H, J=6.9 Hz, H-1); 7.67 (t, 1H, J=7.57 Hz, H-2); 7.36 (m, 1H, H-3); 5.52 (m, 1H, H-1); 5.00 (m, 1H, H-7); 4.27 (m, 1H, H-4); 4.19 (m, 1H, H-5); 3.95 (s, 3H, ArOMe); 3.91-3.50 (m, 23H, H-3, H-6, CH.sub.2O); 3.33 (s, 3H, OMe); 3.13-3.10 (m, 1H, H-10/1); 2.81-2.77 (m, 1H, H-10/2); 2.38 (s, 3H, H-14); 2.35 (m, 1H, H-8/1); 2.18-2.00 (m, 3H, H-2, H-8/2)

EXAMPLE 6

[0069] [(4S,5S)-5-[2-(1,3-dioxolan-2-yl)-1-hydroxyethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate; formula (VII); R.sub.7R.sub.5CH.sub.2; R.sub.9R.sub.10CH.sub.3; XO; Y[CHOH]

[0070] A solution of 4.20 g (0.17 mol) of magnesium turnings and 2 mg (0.015 mmol) of elemental iodine in 200 mL of THF is heated to boiling under argon for 10 min. Subsequently, 26 g (0.15 mol) of 2-bromomethyl-1,3-dioxolane (V) are added dropwise until the onset of the reaction becomes apparent. The rest of the 2-bromomethyl-1,3-dioxolane (V) is metered in subsequently such that the reaction mixture boils gently. After the addition has ended, the reaction mixture is stirred at 80 C. for 2 h. Thereafter, 20 g (0.08 mol) of [(4S,5R)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate (VI), dissolved in 30 mL of THF, are added dropwise to the reaction mixture and the mixture is stirred at room temperature for 6 h. 200 mL of saturated NH.sub.4Cl solution and 200 mL of ice are added to the reaction mixture, which is stirred for 5 min. Subsequently, 300 mL of ethyl acetate are added, phases are separated and the aqueous phase is extracted with 100 mL of ethyl acetate. The combined organic phases are washed with 100 mL of saturated NH.sub.4Cl solution, dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation. 25 g (92%) of yellow oil (51:49 mixture of the diastereomers of 3) are obtained.

[0071] .sup.1H NMR (diastereomer 1), (500 MHz, CDCl.sub.3): (ppm)=8.06 (m, 2H, Ar); 7.56 (m, 1H, Ar); 7.44 (m, 2H, Ar); 5.09 (m, 1H, H-1); 4.66 (dd, J1=11.6 Hz, J2=2.5 Hz, 1H, H-6/1); 4.39 (dd, J1=11.6 Hz, J2=5.6 Hz, 1H, H-6/2); 4.31 (m, 1H, H-5); 4.08-3.80 (m, 6H, H-4, H-3, 2OCH.sub.2); 2.18-2.14 (m, 1H, H-2/1); 1.90-1.81 (m, 1H, H-2/2); 1.42 (s, 3H, MeC); 1.41 (s, 3H, MeC)

[0072] .sup.1H NMR (diastereomer 2), (500 MHz, CDCl.sub.3): (ppm)=8.06 (m, 2H, Ar); 7.56 (m, 1H, Ar); 7.44 (m, 2H, Ar); 5.09 (m, 1H, H-1); 4.55 (m, 1H, H-6/1); 4.48-4.31 (m, 2H, H-6/2, H-5); 4.08-3.80 (m, 6H, H-4, H-3, 2OCH.sub.2); 2.03-1.92 (m, 2H, H-2/1, H-2/2); 1.45 (s, 3H, MeC); 1.44 (s, 3H, MeC)

EXAMPLE 7

[0073] [(4S,5R)-5-[2-(1,3-dioxolan-2-yl)acetyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate; formula (VII); R.sub.7R.sub.5CH.sub.2; R.sub.9R.sub.10CH.sub.3; XO; Y[C(O)]

[0074] A solution of 22.7 mL (0.31 mol) of DMSO and 10 mL of dichloromethane is cooled to 70 C., and 18.53 g (0.14 mol) of oxalyl chloride are slowly added dropwise under inert gas, in such a way that the temperature does not exceed 60 C. The reaction mixture is stirred at 70 C. for 50 minutes. Subsequently, 34.22 g (0.1 mol) of [(4S,5S)-5-[2-(1,3-dioxolan-2-yl)-1-hydroxyethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate (II) dissolved in 20 mL of dichloromethane are added dropwise, making sure that the temperature does not exceed 60 C. Subsequently, the reaction mixture is stirred at 70 C. for 50 min. Thereafter, 79.84 g (0.73 mol) of triethylamine are added dropwise and the mixture is stirred at 70 C. for a further 30 min. The reaction mixture is then warmed gradually to room temperature and 250 mL of H.sub.2O and 200 mL of dichloromethane are added. The phases are separated and the aqueous phase is extracted once with 100 mL of dichloromethane. The combined organic phases are washed once with 100 mL of sulfuric acid (0.1% in H.sub.2O), once with 100 mL of saturated NaHCO.sub.3 solution (and once with 100 mL of saturated NaCl solution), dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation. 33.73 g (99%) of colorless oil are obtained.

[0075] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=8.02 (d, J=7.2 Hz, 2H, Ar); 7.53 (t, J=7.2 Hz, 1H, Ar); 7.41 (t, J=7.6 Hz, 2H, Ar); 5.30 (t, J=5.2 Hz, 1H, H-1); 4.62 (dd, J1=11.6 Hz, J2=3.1 Hz, 1H, H-6/1); 4.37 (m, 3H, H-4, H-5, H-6/2); 3.94 (m, 2H, OCH.sub.2); 3.83 (m, 2H, OCH.sub.2); 3.04 (d, J=5.3, 2H, H-2/1, H-2/2); 1.44 (s, 3H, MeC); 1.41 (s, 3H, MeC)

EXAMPLE 8

[0076] [(4S,5S)-5-[(E)-C-(1,3-dioxolan-2-ylmethyl)-N-hydroxy-carbonimidoyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate; formula (VII); R.sub.7R.sub.8CH.sub.2; R.sub.9R.sub.10CH.sub.3; XO; Y[C(N)OH]

[0077] To a solution of 24.52 g (0.07 mol) of [(4S,5R)-5-[2-(1,3-dioxolan-2-yl)acetyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate (II) in 80 mL of pyridine are added 31.58 g (0.45 mol) of hydroxylamine hydrochloride (NH.sub.2OH. HCl). This is followed by stirring under inert gas at 55 C. for 13 h. The pyridine is removed by means of a rotary evaporator and the residue is then dried under high vacuum. Thereafter, 250 mL of H.sub.2O and 250 mL of ethyl acetate are added and the phases are separated. The aqueous phase is extracted four times with ethyl acetate (450 mL). The combined organic phases are washed with saturated NaCl solution and dried over sodium sulfate, filtered and concentrated by evaporation. 24.24 g (94%) of yellow oil are obtained.

[0078] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=8.05 (d, J=7.2 Hz, 2H, Ar); 7.56 (t, J=7.2 Hz, 1H, Ar); 7.43 (t, J=7.7 Hz, 2H, Ar); 5.31 (t, J=4.7 Hz, 1H, H-1); 4.58 (m, 3H, H-4, H-5, H-6/1); 4.40 (m, 1H, H-6/2); 3.98 (m, 2H, OCH.sub.2); 3.84 (m, 2H, OCH.sub.2); 2.78 (m, 2H, H-2/1, H-2/2); 1.46 (s, 6H, Me.sub.2C)

EXAMPLE 9

[0079] 2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanone oxime; formula (II); R.sub.7R.sub.8CH.sub.2; R.sub.9R.sub.10CH.sub.3; R.sub.4H; XO; Y[C(N)OH]

[0080] To a solution of 16.0 g (43.79 mmol) of [(4S,5S)-5-[(E)-C-(1,3-dioxolan-2-ylmethyl)-N-hydroxycarbon-imidoyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methyl benzoate (II) in 340 mL of THF/H.sub.2O (1:1) are added dropwise 32 mL of 2N NaOH (63.96 mmol), and the mixture is stirred at 60 C. for 18 h. After cooling to room temperature, 200 mL of MTBE are added, the phases are separated and the aqueous phase is extracted four times with MTBE. The combined organic phases are washed with saturated NaCl solution and dried over sodium sulfate, filtered and concentrated. 9.31 g (81%) of yellow oil are obtained.

[0081] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=9.07 (s, 1H, OH); 5.35 (t, J=5.3 Hz, 1H, H-1); 4.45 (d, J=8.5 Hz, 1H, H-4); 4.27 (m, 1H, H-5); 3.97 (m, 2H, OCH.sub.2); 3.78 (m, 3H, OCH.sub.2, H-6); 3.09 (s, 1H, OH); 2.74 (m, 2H, H-2/1, H-2/2); 1.43 (s, 6H, Me.sub.2C)

EXAMPLE 10

[0082] 2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]ethanone oxime; formula (II); R.sub.7R.sub.8CH.sub.2; R.sub.9R.sub.10CH.sub.3; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[C(N)OH]

[0083] To a solution of 7.8 g (29.9 mmol) of 2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanone oxime (II) in 150 mL of THF are added 2.26 g of sodium hydride (95%) (89.8 mmol) in portions and the mixture is stirred at room temperature under inert gas for 1.5 h. Subsequently, 24.3 g (60 mmol) of 2-[2-[2-[2-(2-methoxyethoxy)ethoxy]-ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate dissolved in 50 mL of THF are added dropwise and the mixture is stirred at 60 C. for a further 5 h. The reaction is then quenched with saturated NH.sub.4Cl solution. Thereafter, 300 mL of DCM are added, the phases are separated and the aqueous phase is extracted four times with DCM. The combined organic phases are dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation. The resulting oil is purified by chromatography (eluent: toluene/acetone 2:1->1:1, v/v). 12.4 g (84%) of yellow oil are obtained.

[0084] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=5.32 (t, J=5.3 Hz, 1H, H-1); 4.38 (m, 1H, H-5); 4.28 (d, J=8.2 Hz, 1H, H-4); 3.95 (m, 2H, OCH.sub.2); 3.82 (m, 2H, OCH.sub.2); 3.64 (m, 18H, CH.sub.2O); 3.52 (m, 4H, H-6, MeOCH.sub.2); 3.35 (s, 3H, OMe); 2.73 (d, J=5.7 Hz, 2H, H-2/1, H-2/2); 1.42 (s, 3H, MeC); 1.40 (s, 3H, MeC)

EXAMPLE 11

[0085] (1S)-2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]ethanamine; formula (II); R.sub.7R.sub.8CH.sub.2; R.sub.9R.sub.10CH.sub.3; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNH.sub.2]; Y[CHNR.sub.5R.sub.6], R.sub.5R.sub.6H

[0086] A solution of 12.4 g (25 mmol) of 2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]-ethoxy]ethoxy]ethoxymethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]ethanone oxime (II) in 125 mL of THF under inert gas is cooled to 0 C. Connecting, 3.1 g (82.2 mmol) of lithium aluminum hydride (LiAlH.sub.4) are added gradually while stirring. This is followed by stirring at RT for 4 h. The reaction is quenched with NaOH solution (5M), 100 mL of EtOAc are added and the mixture is stirred for 10 min. The reaction mixture is then filtered and the phases are separated. The combined organic phases are washed with saturated NaCl solution and dried over sodium sulfate, filtered and concentrated by evaporation. 9.8 g (81%) of yellow oil (mixture of the diastereomers 57:43 of 3) are obtained.

[0087] .sup.1H NMR (200 MHz; CDCl.sub.3): (ppm)=5.01 (t, J=4.73 Hz, 1H, H-1); 4.20-3.77 (m, 7H, H-4, H-5, H-6, 2OCH.sub.2); 3.64 (m, 18H, CH.sub.2O); 3.53 (m, 2H, MeOCH.sub.2); 3.35 (s, 3H, OMe); 3.19-3.00 (m, 1H, H-3); 2.24-1.56 (m, 2H, H-2); 1.38 (s, 3H, MeC); 1.37 (s, 3H, MeC)

EXAMPLE 12

[0088] N-[2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]-2,2,2-trifluoro-acetamide; formula (II); R.sub.7R.sub.8CH.sub.2; R.sub.9R.sub.10CH.sub.3; R.sub.4[(CH.sub.2CH.sub.2O).sub.5CH.sub.3]; XO; Y[CHNR.sub.5R.sub.6], R.sub.5H, R.sub.6[C(O)CF.sub.3]

[0089] To a solution of 9.8 g (20.3 mmol) of (1S)-2-(1,3-dioxolan-2-yl)-1-[(4S,5S)-5-[2-[2-[2-[2-(2-methoxy-ethoxy)ethoxy]ethoxy]ethoxy]ethoxymethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]ethanamine (II) in 196 mL of DCM and 9.6 mL of pyridine is added 0.05 g (0.4 mmol) of 4-(dimethylamino)pyridine. The reaction mixture is cooled to 17 C. and 6.41 g (30.5 mmol) of trifluoroacetic anhydride are added dropwise. Thereafter, the mixture is warmed to room temperature within 4 h while stirring, all the solvents are concentrated by evaporation and the residue is taken up in dichloromethane. The organic phase is washed with semi-saturated NaHCO.sub.3 solution and saturated NaCl solution, dried over sodium sulfate, filtered and concentrated by evaporation. The resulting oil is purified by chromatography (eluent: petroleum ether/acetone 2:1, v/v). 9.5 g (80%) of yellow oil (mixture of the diastereomers 57:43 of 3) are obtained.

[0090] .sup.1H NMR (diastereomer 1), (500 MHz; CDCl.sub.3): (ppm)=7.65 (d, J=8.85 Hz, 1H, NH); 4.99 (t, J=4.6 Hz, 1H, H-1); 4.30 (m, 1H, H-3); 3.92 (m, 7H, H-4, H-5, H-6, 2OCH.sub.2); 3.62 (m, 18H, CH.sub.2O); 3.52 (m, 2H, MeOCH.sub.2); 3.35 (s, 3H, OMe); 2.04 (m, 2H, H-2); 1.38 (s, 3H, MeC); 1.37 (s, 3H, MeC)

[0091] .sup.1H NMR (diastereomer 2), (500 MHz; CDCl.sub.3): (ppm)=6.95 (d, J=9.15 Hz, 1H, NH); 4.96 (t, J=4.4 Hz, 1H, H-1); 4.40 (m, 1H, H-3); 3.92 (m, 7H, H-4, H-5, H-6, 2OCH.sub.2); 3.62 (m, 18H, CH.sub.2O); 3.52 (m, 2H, MeOCH.sub.2); 3.35 (s, 3H, OMe); 2.04 (m, 2H, H-2); 1.38 (s, 3H, MeC); 1.1.37 (s, 3H, MeC)

EXAMPLE 13

[0092] (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)silyl)-oxyethyl]-1,3-dioxolan-4-one; formula (IX)

[0093] 40 g of 2-[(2S,4S)-2-tert-butyl-5-oxo-1,3-dioxolan-4-yl] acetic acid are dissolved in 300 mL of THF under an argon atmosphere and cooled to 0 C. 238 mL of BH.sub.3.THF complex (1M in THF) are added gradually within one hour, in such a way that the temperature does not rise above 5 C. On completion of addition of the reagent, the reaction mixture is stirred at 0 C. for 20 min, warmed to room temperature and stirred for 3.5 hours. The reaction mixture is partitioned between saturated NH.sub.4Cl solution and EtOAc. The phases are separated and the aqueous phase is extracted with EtOAc. The combined organic phases are washed with 5% aqueous NaHCO.sub.3 solution and saturated sodium chloride solution, dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. 32 g of intermediate are obtained, which can be used directly in the next stage without further purification.

[0094] 43 g of TBDMSCl in 500 mL of DCM are admixed with 45.1 g of pyridine. The solution is stirred for 10 min, then the intermediate, dissolved in 100 mL of DCM, is added. The reaction mixture is stirred at room temperature for 16 hours and then poured onto water. The phases are separated, the organic phase is washed with 5% aqueous NaHCO.sub.3 solution, dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. The crude product is purified by means of flash chromatography over silica gel with toluene as eluent. 52.3 g of (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-1,3-dioxolan-4-one are obtained as a colorless oil.

[0095] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=5.15 (s, 1H, H-5); 4.43 (dd, 1H, 3.8 Hz, 8.5 Hz, H-3); 3.80 (m, 2H, H-1); 2.12 (m, 1H, H-2/1); 1.86 (m, 1H, H-2/2); 0.97 (s, 9H, H-tBuCH.sub.3); 0.89 (s, 9H, H-SitBuCH.sub.3); 0.06 (s, 6H, HSiCH.sub.3).

EXAMPLE 14 (ALKYLATION REACTION)

[0096] (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)silyl)-oxyethyl]-5-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-one; formula (X); R.sub.1H

[0097] To a solution of 18 g of KHMDS in 680 mL of anhydrous THF is added dropwise, under an argon atmosphere at 76 C., a solution of 25.6 g of (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-1,3-dioxolan-4-one in 30 mL of THF, in such a way that the temperature does not rise above 72 C. The reaction mixture is stirred at 76 C. for 50 minutes. A solution of 22 g of 2-(bromomethyl)-1,4,9,10-tetramethoxyanthracene in 40 mL of THF is added dropwise at 75 C. The mixture is then stirred at this temperature for 20 min. The reaction mixture is partitioned between 1N HCl and EtOAc. The aqueous phase is extracted with EtOAc and the combined organic phases are dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. The crude product is digested in a mixture of 50 mL of MTBE and 200 mL of PE, filtered and washed with PE. 23.4 g of (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-5-[(1,4,9,10-tetra-methoxy-2-anthryl)methyl-1,3-dioxolan-4-one are obtained as a yellow solid. The filtrate is concentrated by evaporation under reduced pressure and separated by means of column chromatography (silica gel, toluene/EtOAc 30/1). In this way, a further 7.4 g of (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)-silyl)oxyethyl]-5-[(1,4,9,10-tetramethoxy-2-anthryl)-methyl-1,3-dioxolan-4-one are obtained.

[0098] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=8.35 (m, 2H, H-5 and H-8); 7.52 (m, 2H, H-6 and H-7); 6.64 (s, 1H, H-3); 4.84 (s, 1H, H-acetal); 4.02 (s, 3H, OCH.sub.3-4); 4.00 (s, 3H, OCH.sub.3-10); 3.95 (s, 3H, OCH.sub.3-9); 3.83 (m, 2H, H-4); 3.75 (s, 3H, OCH.sub.3-1); 3.44 (d, 1H, J=13.9 Hz, H-1/1); 3.18 (d, 1H, J=13.9 Hz, H-1/2); 2.17 (m, 2H, H-3); 0.89 (s, 9H, H-tBuCH.sub.3); 0.88 (s, 9H, H-SitBuCH.sub.3); 0.05 (s, 3H, HSiCH.sub.3); 0.04 (s, 3H, HSiCH.sub.3).

EXAMPLE 15

[0099] (3S)-5-(tert-Butyl(dimethyl)silyl)oxy-3-hydroxy-3-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]pentan-2-one; formula (XI); R.sub.1H

[0100] To a solution of 62 g of (2S,5S)-2-tert-butyl-5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-5-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-one in 700 mL of anhydrous THF are added dropwise, under an argon atmosphere at 78 C., 164 mL of MeLi (1.6 M in Et.sub.2O), in such a way that the temperature does not rise above 71 C. The reaction mixture is stirred at 75 C. for 1.5 hours and then partitioned between saturated NH.sub.4Cl solution and EtOAc. The aqueous phase is extracted with EtOAc. The combined organic phases are dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. The crude product is purified by means of column chromatography (silica gel, toluene/EtOAc, 10/1). 54.2 g of (3S)-5-(tert-butyl-(dimethyl)silyl)oxy-3-hydroxy-3-[(1,4,9,10-tetra-methoxy-2-anthryl)methyl]pentan-2-one are obtained as a yellow foam.

[0101] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=16.67 (m, 2H, H-5 and H-8); 7.51 (m, 2H, H-6 and H-7); 6.70 (s, 1H, H-3); 4.01 (s, 3H, OCH.sub.3-4); 3.98 (s, 3H, OCH.sub.3-10); 3.92 (s, 3H, OCH.sub.3-9); 3.82 (td, 1H, J=4.1 Hz, 9.2 Hz, H-4/1); 3.77 (s, 3H, OCH.sub.3-1); 3.70 (dt, 1H, J =5.1 Hz, 10.4 Hz, H-4/2); 3.27 (d, 1H, J=12.9 Hz, H-1/1); 3.12 (d, 1H, J=12.9 Hz, H-1/2); 2.39 (m, 1H, H-3/1); 2.33 (s, 3H, CH.sub.3); 1.96 (dt, 1H, J=4.4 Hz, 14.2 Hz, H-3/2); 0.86 (s, 9H, H-SitBuCH.sub.3); 0.02 (s, 3H, HSiCH.sub.3); 0.01 (s, 3H, HSiCH.sub.3).

EXAMPLE 16

[0102] a. Reduction of the Keto Group

(2S,3S)-5-(tert-Butyl(dimethyl)silyl)oxy-3-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]pentane-2,3-diol

[0103] To a solution of 33.8 g of (3S)-5-(tert-butyl-(dimethyl)silyl)oxy-3-hydroxy-3-[(1,4,9,10-tetra-methoxy-2-anthryl)methyl]pentan-2-one in 340 mL of EtOH are added, under an argon atmosphere, 2.36 g of NaBH.sub.4. The reaction mixture is stirred at RT for one hour and then quenched with saturated sodium chloride solution and EtOAc. The aqueous phase is extracted with EtOAc. The combined organic phases are dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. The crude product is purified by means of flash chromatography (silica gel, toluene/EtOAc=5:1). 30.70 g (2S,3S)-5-(tert-butyl(dimethyl)silyl)oxy-3-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]pentane-2,3-diol are obtained as a yellow foam.

b. Ketalization:

[0104] tert-Butyldimethyl-[2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]ethoxy]silane; formula (XII), R.sub.1H

[0105] To a solution of 5.26 g of the alcoholic intermediate in 100 mL of dry acetone are added, under an argon atmosphere, 2.6 mL of dimethoxypropane followed by 0.09 g of pTsOH. The reaction mixture is stirred at RT for 1.5 hours and then partitioned between saturated NaHCO.sub.3 solution and EtOAc. The phases are separated: the aqueous phase is extracted with EtOAc. The combined organic phases are dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. The crude product is purified by means of flash chromatography (silica gel, toluene/EtOAc, 40/1). 4.66 g of tert-butyldimethyl-[2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]ethoxy]silane are obtained as a yellow foam.

[0106] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=8.35 (m, 2H, H-5 and H-8); 7.50 (m, 2H, H-6 and H-7); 6.97 (s, 1H, H-3); 4.54 (q, 1H, J=6.3 Hz, H-5); 4.02 (s, 3H, OCH.sub.3-4); 3.98 (s, 3H, OCH.sub.3-10); 3.92 (s, 3H, OCH.sub.3-9); 3.73 (s, 3H, OCH.sub.3-1); 3.69 (m, 2H, H-4); 3.19 (d, 1H, J=13.6 Hz, H-1/1); 2.75 (d, 1H, J=13.6 Hz, H-1/2); 1.91 (m, 1H, H-3/1); 1.77 (m, 1H, H-3/2); 1.74 (s, 3H, H-acetonide); 1.45 (d, 3H, J=6.3 Hz, CH.sub.3); 1.44 (s, 3H, H-acetonide); 0.86 (s, 9H, H-SitBuCH.sub.3); 0.01 (s, 6H, HSiCH.sub.3).

EXAMPLE 17

[0107] a. Detachment of the TBDMS Group

2-[(4S,5S)-2,2,5-Trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]ethanol

[0108] To a solution of 4.57 g of tert-butyldimethyl-[2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]ethoxy]silane in 90 mL of anhydrous THF are added at RT, under an argon atmosphere, 19.5 mL of TBAF (1M in THF). The reaction mixture is stirred at RT for 1 hour. The reaction mixture is partitioned between saturated NaHCO.sub.3 solution and EtOAc. The aqueous phase is extracted with EtOAc. The combined organic phases are dried over Na.sub.2SO.sub.4, filtered and concentrated by evaporation under reduced pressure. 603 g of 2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]ethanol are obtained as a yellow foam.

[0109] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=8.35 (m, 2H, H-5 and H-8); 7.51 (m, 2H, H-6 and H-7); 6.93 (s, 1H, H-3); 4.37 (q, 1H, J=6.3 Hz, H-5); 4.02 (s, 3H, OCH.sub.3-4); 4.00 (s, 3H, OCH.sub.3-10); 3.93 (s, 3H, OCH.sub.3-9); 3.81 (m, 1H, H-4/1); 3.78 (s, 3H, OCH.sub.3-1); 3.66 (m, 1H, H-4/2); 3.22 (d, 1H, J=13.6 Hz, H-1/1; 2.81 (brs, 1H, OH-4); 2.75 (d, 1H, J=13.6 Hz, H-1/2); 1.88 (m, 2H, H-3); 1.75 (s, 3H, H-acetonide); 1.48 (d, 3H, J=6.3 Hz, CH.sub.3); 1.47 (s, 3H, H-acetonide).

b. Oxidation of the Primary Alcohol to the Aldehyde:

[0110] 2-[(4S,5S)-2,2,5-Trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]acetaldehyde; formula (XIII); R.sub.1H

[0111] Added dropwise to a solution of 0.99 mL of DMSO in 55 mL of DCM at 70 C. is 0.61 mL of oxalyl chloride under an argon atmosphere. The mixture is stirred at 70 C. for 1 hour. Subsequently, 2.19 g of 2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)-methyl]-1,3-dioxolan-4-yl]ethanol in 4 mL of DCM are added gradually at 70 C. The reaction mixture is stirred for 1 hour. 4.27 mL of Et.sub.3N are added at the same temperature. Stirring is continued while gradually warming to 0 C. for another 1 hour. The reaction mixture is partitioned between saturated sodium chloride solution and EtOAc. The organic phase is washed successively with saturated NH.sub.4Cl solution, saturated NaHCO.sub.3 solution and saturated sodium chloride solution, dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. 2.1 g of 2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]acetaldehyde are obtained as a yellow foam.

[0112] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=9.65 (dd, 1H, J=1.3 Hz, 2.2 Hz, H-4); 8.34 (m, 2H, H-5 and H-8); 7.51 (m, 2H, H-6 and H-7); 6.81 (s, 1H, H-3); 4.28 (q, 1H, J=6.3 Hz, H-5); 4.03 (s, 3H, OCH.sub.3-4); 3.99 (s, 3H, OCH.sub.3-10); 3.91 (s, 3H, OCH.sub.3-9); 3.70 (s, 3H, OCH.sub.3-1); 3.23 (d, 1H, J=13.6 Hz, H-1/1); 2.77 (dd, 1H, J=2.2 Hz, 16.4 Hz, H-3/1); 2.73 (d, 1H, J=13.6 Hz, H-1/2); 2.62 (dd, 1H, J=1.3 Hz, 16.34 Hz, H-3/2); 1.74 (s, 3H, H-acetonide); 1.55 (d, 3H, J=6.3 Hz, CH.sub.3); 1.40 (s, 3H, H-acetonide).

c. Oxidative Demethylation:

[0113] 2-[(4S,5S)-4-[(1,4-dimethoxy-9,10-dioxo-2-anthryl)-methyl]-2,2,5-trimethyl-1,3-dioxolan-4-yl]acetaldehyde; formula (XIV), R.sub.1H

[0114] To a solution of 2.08 g of 2-[(4S,5S)-2,2,5-trimethyl-4-[(1,4,9,10-tetramethoxy-2-anthryl)methyl]-1,3-dioxolan-4-yl]acetaldehyde in 60 mL of CH.sub.3CN is added, at 2 C., a solution of 7.3 g of CAN in 130 mL of water. After stirring for 30 min, the reaction mixture is diluted with 80 mL of water. The aqueous phase is extracted with EtOAc. The combined organic phases are dried and concentrated by evaporation. The resulting mixture is separated by chromatography (eluent: toluene/EtOAc 6:1). 1.91 g of 2-[(4S,5S)-4-[(1,4-dimethoxy-9,10-dioxo-2-anthryl)methyl]-2,2,5-trimethyl-1,3-dioxolan-4-yl]acetaldehyde are obtained as a yellow solid.

[0115] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=9.62 (dd, 1H, J=1.6 Hz, 2.5 Hz, H-4); 8.16 (m, 2H, H-5 and H-8); 7.71 (m, 2H, H-6 and H-7); 7.45 (s, 1H, H-3); 4.25 (q, 1H, J=6.3 Hz, H-5); 4.00 (s, 3H, OCH.sub.3-4); 3.81 (s, 3H, OCH.sub.3-1); 3.18 (d, 1H, J=12.9 Hz, H-1/1); 2.66 (d, 1H, J=12.9 Hz, H-1/2); 2.65 (dd, 1H, J=2.5 Hz and 16.4 Hz, H-3/1); 2.48 (dd, 1H, J=1.6 Hz, 16.4 Hz, H-3/2); 1.64 (s, 3H, H-acetonide); 1.50 (d, 3H, J=6.3 Hz, CH.sub.3); 1.34 (s, 3H, H-acetonide).

EXAMPLE 18

[0116] 2-[[(2S,3S)-3,5-dihydroxy-2-methyltetrahydrofuran-3-yl]methyl]-1,4-dihydroxyanthracene-9,10-dione; formula (XV); R.sub.1H

[0117] To a solution of 1 g of 2-[(4S,5S)-4-[(1,4-dimethoxy-9,10-dioxo-2-anthryl)methyl]-2,2,5-trimethyl-1,3-dioxolan-4-yl]acetaldehyde in 55 mL of DCM are added dropwise at 2 C., under an argon atmosphere, 13.7 mL of BCl.sub.3 (1M in DCM). The reaction mixture is stirred for 40 min, and 0.5 N NaOH and DCM are added. The phases are separated; the organic phase is washed with 0.5 N NaOH. The combined aqueous phases are acidified to pH=6 at 0 C. with 1 N HCl and extracted with DCM. The combined organic phases are dried and concentrated by evaporation. 0.79 g of 2-[[(2S,3S)-3,5-dihydroxy-2-methyltetrahydrofuran-3-yl]methyl]-1,4-dihydroxy-anthracene-9,10-dione is obtained as a red solid.

[0118] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=13.66 (s, 1H, OH-1); 12.87 (s, 1H, OH-4); 8.36 (m, 2H, H-5 and H-8); 7.85 (m, 2H, H-6 and H-7); 7.29 (s, 1H, H-3); 5.38 (m, 1H, H-4); 4.01 (q, 1H, J=6.3 Hz, H-6); 3.52 (d, 1H, J=7.3 Hz, OH-4); 3.39 (s, 1H, OH-2); 3.07 (d, 1H, J=13.6 Hz, H-1/1); 2.90 (d, 1H, J=13.6 Hz, H-1/2); 2.21 (dd, 1H, J=5.1, 13.3 Hz, H-3/1; 1.99 (d, 1H, J=13.3 Hz, H-3/2); 1.34 (d, 3H, J=6.3 Hz, CH.sub.3).

EXAMPLE 19

[0119] a. Intramolecular Ring Closure as Per Marschalk

[0120] (7R,9S)-6,7,9,11-tetrahydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione; formula (XVI); R.sub.1, R.sub.13H; R.sub.12OH and (7S,9S)-6,7,9,11-tetrahydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione; formula (XVI); R.sub.1, R.sub.12H; R.sub.13OH

[0121] To a solution of 70 mg of 2-[[(2S,3S)-3,5-dihydroxy-2-methyltetrahydrofuran-3-yl]methyl]-1,4-dihydroxy-anthracene-9,10-dione in 5 mL of THF and 5 mL of MeOH is added dropwise, under an argon atmosphere at 10 C., a solution of 38 mg of NaOH and 49 mg of Na.sub.2S.sub.2O.sub.4 in 1.2 mL of water. After stirring for two hours, the reaction mixture is quenched by blowing air in for 30 min. The reaction mixture is admixed with 0.05 N HCl and EtOAc. The phases are separated; the aqueous phase is extracted with EtOAc. The combined organic phases are dried and concentrated by evaporation. The resulting mixture is separated by chromatography (eluent: toluene/isopropanol 30:1). 37 mg of a mixture of (7R,9S)-6,7,9,11-tetrahydroxy-9-[(1 S)-1-hydroxy-ethyl]-8,10-dihydro-7H-tetracene-5,12-dione and (7S,9S)-6,7,9,11-tetrahydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione are obtained as a red solid.

(7R,9S)-6,7,9,11-tetrahydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione

[0122] .sup.1H NMR (500 MHz; CDCl.sub.3): =13.60 (s, 1H, OH-6); 13.33 (s, 1H, OH-11); 8.23 (m, 2H, H-1 and H-4); 7.95 (m, 2H, H-2 and H-3); 5.17 (d, 1H, J=5.7 Hz, OH-7); 5.05 (m, 1H, H-7); 4.85 (d, 1H, J=5.7 Hz, OH-13); 4.45 (s, 1H, OH-9); 3.54 (q, 1H, J=6.3 Hz, H-13); 2.85 (d, 1H, J=18.3 Hz, H-10/1); 2.68 (d, 1H, J=18.3 Hz, H-10/2); 2.14 (m, 1H, H-8/1); 1.75 (m, 1H, H-8/2); 1.14 (d, 3H, J=6.3 Hz, CH.sub.3).

(7S,9S)-6,7,9,11-tetrahydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione

[0123] .sup.1H NMR (500 MHz; CDCl.sub.3): =13.42 (s, 1H, OH-6); 13.30 (s, 1H, OH-11); 8.23 (m, 2H, H-1 and H-4); 7.95 (m, 2H, H-2 and H-3); 5.30 (d, 1H, J=7.9 Hz, OH-7); 5.14 (s, 1H, OH-9); 5.00 (m, 1H, H-7); 4.81 (d, 1H, J=5.7 Hz, OH-13); 3.54 (q, 1H, 6.3 Hz, H-13); 2.88 (d, 1H, J=18.3 Hz, H-10/1); 2.75 (d, 1H, J=18.3 Hz, H-10/2); 2.14 (m, 1H, H-8/1); 1.75 (m, 1H, H-8/2); 1.16 (d, 3H, J=6.3 Hz, CH.sub.3).

b. Intramolecular Ring Closure as Per Marschalk

[0124] (9R)-6,9,11-trihydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione; formula (XVI); R.sub.1, R.sub.12, R.sub.13H

[0125] To a solution of 0.79 g of 2-[[(2S,3S)-3,5-Dihydroxy-2-methyltetrahydrofuran-3-yl]methyl]-1,4-dihydroxy-anthracene-9,10-dione in 31 mL of THF and 31 mL of MeOH is added dropwise, under an argon atmosphere at RT, a solution of 0.43 g of NaOH and 0.56 g of Na.sub.2S.sub.2O.sub.4 in 5.3 mL of water. After stirring for 1.5 hours, the reaction mixture is quenched by blowing in air for 30 min. The reaction mixture is admixed with 0.05 N HCl and EtOAc. The phases are separated; the aqueous phase is extracted with EtOAc. The combined organic phases are dried and concentrated by evaporation. The resulting mixture is purified by digesting with toluene/EtOAc (1:1). 0.51 g of (9R)-6,9,11-trihydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione is obtained as a red solid.

[0126] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=13.36 (s, 1H, OH-11); 13.35 (s, 1H, OH-6); 8.21 (m, 2H, H-1 and H-4); 7.94 (m, 2H, H-2 and H-3); 4.69 (d, 1H, J=6.3 Hz, OH-13); 4.28 (s, 1H, OH-9); 3.56 (m, 1H, H-13); 2.82 (d, 1H, J=18.3 Hz, H-7/1); 2.66 (m, 3H, H-7/2 and H-10); 1.88 (m, 1H, H-8/1); 1.51 (m, 1H, H-8/2); 1.14 (d, 3H, J=6.3 Hz, CH.sub.3).

EXAMPLE 20

a: Oxidation of the Side Chain Hydroxyl Group

[0127] (9R)-9-Acetyl-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione; formula (XVII); R.sub.1H

[0128] To a solution of 0.8 g of (9R)-6,9,11-trihydroxy-9-[(1S)-1-hydroxyethyl]-8,10-dihydro-7H-tetracene-5,12-dione (0.80 g, 2.258 mmol) in 45 mL of DCM are added, at RT under an argon atmosphere, 1.58 g of Dess-Martin periodinane (97%). After stirring for 5 hours, the reaction mixture is admixed with saturated NaHCO.sub.3 solution and EtOAc. The phases are separated; the aqueous phase is extracted with EtOAc. The combined organic phases are dried and concentrated by evaporation. The resulting mixture is separated by chromatography (eluent: DCM/EtOAc 7:1). 0.60 g of (9R)-9-acetyl-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione (1.694 mmol, 75%) is obtained as a red solid.

[0129] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=13.48 (s, 1H, OH-11); 13.47 (s, 1H, OH-6); 8.35 (m, 2H, H-1 and H-4); 7.83 (m, 2H, H-2 and H-3); 3.16 (m, 1H, H-7/1); 3.07 (d, 1H, J=18 Hz, H-10/1); 2.95 (m, 2H, H-10/2 and H-7/2); 2.39 (s, 3H, CH3); 2.00 (m, 2H, H-8).

b: Hydroxylation at C-7

[0130] (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione; formula (IV); R.sub.1R.sub.2H

[0131] To a suspension of 130 mg of (9R)-9-acetyl-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione in 35 mL of CCl.sub.4 are added successively 1 mL of water, 74 mg of NBS and 18 mg of AIBN. The reaction mixture is subsequently heated under reflux for 90 minutes. A further 33 mg of NBS are added and the reaction mixture is heated under reflux for a further 2 hours. The reaction mixture is cooled to 20 C. and diluted with 15 mL of 10% K.sub.2CO.sub.3 solution and 20 mL of THF. After stirring for 10 minutes, the aqueous phase is brought to pH=1 with 1 N HCl and extracted with DCM. The combined organic phases are dried, filtered and concentrated under reduced pressure. The crude product is purified by chromatography on silica gel with toluene/EtOAc (10/1), giving 35 mg of (9R)-9-acetyl-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione, 16 mg of (7R,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione and 48 mg of (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione as a red solid. [00133] (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione

[0132] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=13.53 (s, 1H, OH-6); 13.25 (s, 1H, OH-11); 8.31 (m, 2H, H-1 and H-4); 7.84 (m, 2H, H-2 and H-3); 5.29 (brs, 1H, H-7); 4.58 (s, 1H, OH-9); 3.86 (d, 1H, J=5.0 Hz, OH-7); 3.17 (dd, 1H, J=2.2 Hz, 18.6 Hz, H-10/1); 2.94 (d, 1H, J=18.6 Hz, H-10/2); 2.44 (s, 3H, CH.sub.3); 2.35 (m, 1H, H-8/1); 2.17 (dd, 1H, J=5.1 Hz, 14.5 Hz, H-8/2).

(7R,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione

[0133] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=13.93 (s, 1H, OH-6); 13.30 (s, 1H, OH-11); 8.35 (m, 2H, H-1 and H-4); 7.85 (m, 1H, H-2 and H-3); 5.40 (dd, 1H, J=7.9 Hz, 8.6 Hz, H-7); 4.28 (d, 1H, J=1.6 Hz, OH-7); 3.90 (s, 1H, OH-9); 3.10 (d, 1H, J=18.0 Hz, H-10/1); 2.94 (d, 1H, J=18.0 Hz, H-10/2); 2.41 (s, 3H, CH.sub.3); 2.35 (m, 1H, H-8/1); 2.18 (dd, 1H, J=9.8 Hz, 13.0 Hz, H-8/2).

EXAMPLE 21

Epimerization of (7R,9S)-9-acetyl-6,7,9,11-tetra-hydroxy-8,10-dihydro-7H-tetracene-5,12-dione

[0134] 26 mg of (7R,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione, which may be contaminated with (7S,9S)-9-acetyl-6,7,9,11-tetra-hydroxy-8,10-dihydro-7H-tetracene-5,12-dione, are dissolved in 1.3 mL of TFA. After stirring at RT for two hours, the reaction mixture is admixed with water and extracted with DCM. The combined organic phases are dried and concentrated by evaporation. The crude product is dissolved in 1 mL of acetone. Thereafter, saturated NaHCO.sub.3 solution is added. After stirring for 10 min, the mixture is extracted with DCM. The combined organic phases are dried and concentrated by evaporation. The resulting product is purified by chromatography (eluent: toluene/EtOAc 10:1). 15 mg of (7S,9S)-9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7H-tetracene-5,12-dione are obtained as a red solid.

[0135] .sup.1H NMR (500 MHz; CDCl.sub.3): (ppm)=13.53 (s, 1H, OH-6); 13.25 (s, 1H, OH-11); 8.31 (m, 2H, H-1 and H-4); 7.84 (m, 2H, H-2 and H-3); 5.29 (brs, 1H, H-7); 4.58 (s, 1H, OH-9); 3.86 (d, 1H, J=5.0 Hz, OH-7); 3.17 (dd, 1H, J=2.2 Hz, 18.6 Hz, H-10/1); 2.94 (d, 1H, J=18.6 Hz, H-10/2); 2.44 (s, 3H, CH.sub.3); 2.35 (m, 1H, H-8/1); 2.17 (dd, 1H, J=5.1 Hz, 14.5 Hz, H-8/2).

[0136] The invention further relates to the following items of subject matter/compounds and uses:

[0137] 1. A compound of the general formula (I)

##STR00026##

in which R.sub.1 is a hydrogen atom or a hydroxyl or methoxy group; R.sub.2 is a hydrogen atom or a hydroxyl group; R.sub.3 is hydrogen or a suitable hydroxyl protecting group and the wavy line in each case means both possible configurations of OR.sub.3 in relation to the base structure; Y[C(O)], [C(N)OH] or [CHOH], [CHNR.sub.5R.sub.6] in both possible stereoisomeric arrangements, where R.sub.5 and R.sub.6 are the same or different and are each a hydrogen atom, or a suitable amino protecting group as known in the prior art, for instance from Protective Groups in Organic Synthesis (Greene, Wuts) 4th edition, John Wiley & Sons, Inc., pages 696 to 927, especially a trifluoroacetyl, unbranched or branched lower alkyl, where lower alkyl means a carbon number from 1 to 4, or an alkylene chain (CH.sub.2CZ.sub.2CZ.sub.2CH.sub.2, CH.sub.2CZ.sub.2CZ.sub.2CZ.sub.2CH.sub.2, CH.sub.2OCZ.sub.2CH.sub.2, CH.sub.2OCZ.sub.2CZ.sub.2CH.sub.2, CH.sub.2CZ.sub.2OCZ.sub.2CH.sub.2) where Z is defined as hydrogen, lower alkyl or lower alkoxy in any combination; in which X O, S or NR; where R=hydrogen or lower alkyl; R.sub.4 is an unbranched or branched alkyl or heteroalkyl chain having a chain length of 1 to 19 elements, where a maximum of 6 heteroatoms (O, N, S) in any combination are separated from one another by at least two carbon atoms.

[0138] 2. A compound of the general formula (I) in which XO and R1, R2, R3, R4 and Y are each as defined in item 1.

[0139] 3. A compound of the general formula (I) in which XNR and R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Y are each as defined in item 1.

[0140] 4. A compound of the general formula (I) in which XS and R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Y are each as defined in item f.

[0141] 5. A compound as claimed in items 1 to 4 in which R.sub.4 contains at least one ethylene glycol unit (OCH.sub.2CH.sub.2O).

[0142] 6. A process for preparing compounds of the general formula (I) according to items 1 to 5, characterized in that an open-chain sugar compound of the general formula (II)

##STR00027##

in which R.sub.7 and R.sub.5 are the same and are each alkyl or alkylene having 2 to 3 carbon atoms; R.sub.9 and R.sub.10 are each an alkyl group having 1 to 3 carbon atoms; X and Y are each as defined in formula (I) of item 1; R.sub.4 is hydrogen or a suitable hydroxyl protecting group as known in the prior art, for instance from Protective Groups in Organic Synthesis (Greene, Wuts) 4th edition, John Wiley & Sons, Inc., pages 16 to 288, especially a benzoyl group, or is as defined for R.sub.4 in formula (I), is cyclized to give a sugar compound of the general formula (III)

##STR00028##

in which X, Y and R.sub.4 are each as defined in formula (II), R.sub.3 and R.sub.11 are each an activating group known for glycosylation [C(O)PhNO.sub.2, OTFA] and the wavy lines in each case mean both possible configurations of OR.sub.3 and OR.sub.11 in relation to the base structure, and is reacted with an anthraquinone-derived aglycone of the general formula (IV)

##STR00029##

in which R.sub.1 and R.sub.2 are each as defined in item 1, and then the protecting groups still present on the sugar are detached under basic conditions, preferably with sodium hydroxide solution, in order to obtain compounds of the general formula (I) as per item 1.

[0143] 7. The process as claimed in item 6, characterized in that the compound of the general formula (II) to be cyclized is prepared by joining a C2 unit of the general formula (V)

##STR00030##

in which R.sub.7 and R.sub.8 are each as defined in formula (II) to a protected derivative of L-threose (enantiomerically pure C4 unit) of the general formula (VI)

##STR00031##

in which X, R.sub.4, R.sub.9, R.sub.10 are each as defined in formula (II), by known methods, wherein preference is given to CC bond formation by means of a Grignard reaction in an aprotic solvent such as tetrahydrofuran, and the resulting addition product of the general formula (II) in which [YCHOH] can subsequently be oxidized by known methods such as oxidation with chromium compounds, but preferably by means of Swern oxidation to give the ketone [YC(O)] of the general formula (II),
in order then to introduce the nitrogen at position 3 by known methods, for example by reductive amination, but preferably by preparation of an oxime [YC(N)OH] of the general formula (II), which is subsequently reduced,
but, if R.sub.4 is hydrogen or a hydroxyl protecting group, may be deprotected beforehand if necessary and derivatized according to the description for R.sub.4 in formula (I), in which case the introduction of an unbranched or branched alkyl or heteroalkyl chain on X is effected by known methods, for example Finkelstein reaction, but preferably via a nucleophilic substitution, where the chain to be introduced is activated beforehand with a good leaving groups such as tosylate or mesylate, and then oximes of the general formula (II) [YC(N)OH] are reduced, for which it is possible to use known methods, preferably a complex hydride in an aprotic solvent such as toluene or THF, forming amines of the general formula (II) [YCHNH.sub.2] which are optionally derivatized further or protected at this site [YCHNR.sub.5R.sub.6] where R.sub.5 and R.sub.6 are each as defined in the general formula (I).

[0144] 8. A compound of the general formula (III)

##STR00032##

in which X, Y and R.sub.4 are each as defined in formula (II) and R.sub.6 and R.sub.11 are each hydrogen or an activating group known for glycosylation [OC(O)PhNO.sub.2, OTFA] and the wavy lines in each case mean both possible configurations of OR.sub.3 and OR.sub.11 in relation to the base structure.

[0145] 9. A compound as claimed in item 8, characterized in that R.sub.3 and R.sub.11 are each hydrogen, Y[CHNR.sub.5R.sub.6] where R.sub.5 is hydrogen and R.sub.6 is TFA, XO and R.sub.4 comprises at least one ethylene glycol unit (OCH.sub.2CH.sub.2O).

[0146] 10. A compound as claimed in item 9, characterized in that R.sub.3 and R.sub.11 are each p-nitrobenzoyl.

[0147] 11. A compound of the general formula (II)

##STR00033##

in which R.sub.7 and R.sub.8 are the same and are each alkyl or alkylene having 2 to 3 carbon atoms; R.sub.9 and R.sub.10 are each an alkyl group having 1 to 3 carbon atoms; X and Y are each as defined in formula (I); R.sub.4 is hydrogen or a suitable hydroxyl protecting group as known in the prior art, for instance from Protective Groups in Organic Synthesis (Greene, Wuts) 4th edition, John Wiley & Sons, Inc., pages 16 to 288, especially a benzoyl group, or is as defined in formula (I).

[0148] 12. The use of compounds of the general formula I alone or in combination with other active ingredients in medicaments.

[0149] 13. The use of compounds of the general formula III as a structural element in drugs.