CS196641B1 - Method of preparing novel acetylderivatives of 2,4-dinitrophenyl hydrazones of deoxysaccharides having antitumour actions iii - Google Patents

Description

The invention relates to a process for the preparation of certain derazysaccharide hydrazones and their acetylderivatives as potential cancerostatics. Acetylated hydrazones of saccharides have been found to have antitumor effects (K. Linek, J. Fouska, R. Sandtnerova, M. Kulhanek, U.S. Pat. No. 163115).

This invention relates to the preparation of novel antitumor derivatives. the effects of it

2,4-dinitrophenylhyrazrazones of some deoxysaccharides and their acetylderivatives (Table 1), characterized in that the corresponding saccharide hydrazone is acetylated with acetic anhydride under the catalytic action of pyridine at 0 ° C.

The substances listed in Table 1 have not been described in the literature. Substances were identified by melting point, optical rotation and elemental analysis.

The potential antitumor effects of our compounds were evaluated in in vitro experiments on EAC cells. The effect of the compounds was evaluated by inhibiting the incorporation of ¹⁴ C precursors of protein and nucleic acid synthesis into EAC cell fractions insoluble in glacial trichloroacetic acid, by the method described by J. Fuška et al. Neoplasm 18,631, (1971). In particular, the substances inhibited the synthesis of nucleic acids, in particular RNK (Table 2).

Table 1

P. No Substance b. t. Noc: 2 ° C 1. 2-Deoxy-D-glucose 2,4DNFH 173 to 174 + 28.3 ° 2. 3-Deoxy-D-glucose 2,4DNFH 129 to 131 —36.3 ° 3. 6-Deoxy-D-glucose 2,4D'NFH 177 to 178 —19.8 ° ' 4. 3-Deoxy-D-mannose 2,4DNFH 147 to 149 + 16.6 ° 5. 4-Deoxy-D-mannose 2,4DNFH 170 to 172 —19.1 ° 6. 6-Deoxy-D-mannose 2.4DNFH 168 to 170 —78.8 ° 7. 3,4,5,6-tetra-O-acetyl-2-deoxy-D-glucose 2,4DNFH 127 to 128 + 25.5 ° 8. ' 2,4,5,6-tetra-O-acetyl-3-deoxy-D-glucose 2,4DNFH syrup + 47.9 °

D ²⁵ (C, O, 31, C 6 H 5 N) (C, O, 27, C 2 H 5 OH) (C, O, 30, C 2 H 5 OH) (C, O, 35, CH 3 OH) (C, 0, 28, CH 3 OH) O, 29, CH 3 OH) (C, O, 35, CH 3 COOC 2 H 5) (C, 0, 3, CH 3 COOC 2 H 5)

3 9. 2,3,4,5-tetra-Oiacetyl-6-deoxy-D-glucose 2,4DNFH 162 + 17.7 ° 4 (C, O, 31, CH3COOC2H5) 10. 2,4,5,6-tetra-O-acetyl-3-deoxy-D-mannose 2,4DNFH syrup —30.3 ° (C, 0, 25, CH3COOC2H5) 11. 2,3,5,6-tetra-O-acetyl-4-desokly-D- scab' —27.2 ° (C, 0, 28, GH3GOOG2H5) ! -manose 2.4DNFH (prepared from substance no.7) - - - 12. 2,3,4,5-tetra-O-acetyl-6-deoxy-D-mannose 2.4DNEH 180 to 182 - 7.5 ° (C, O, 30, CH3QDOC2H5)

Preparation of 2,4-dinitrophenyl hydrazones deoxysaccharides mmol of deoxysaccharide is dissolved in 30 ml of ethanol, 1 mmol of 2,4-dlnitrophenylhydrazine and 0.05 ml of acetic acid are added and heated to reflux. The progress of the reaction was monitored by thin layer chromatography on silica gel (silufol) in chloroform: methanol (6: 1). The optimum reaction time is 12-15 hours. The reaction mixture is then concentrated, the residue is extracted with chloroform and the insoluble residue is crystallized from ethanol to give the corresponding hydrazone deoxysaccharide in about 80% yield.

Table 2 Experiment Results - Effect on EAC P. No Substance Inhibition of% incorporation Adenine L-valine 1. 2-Deoxy-D-glucose 2,4DNFH 32.5 8.5 2. 3-Deoxy-D-glucose 2,4DNFH 50.2 16.8 3. 6-Deoxy-D-glucose 2,4DNFH 26,8, + 2,8 4. 3-Deoxy-D-mannose 2,4DNFH 0.0 + 17.3 5. 4-Deoxy-D-mannose 2,4DNEIf 17.8 7.6 6. 6-Deoxy-D-mannose 2,4DNFH 18.2 ; 0.0 7. 3,4,5,6-tetra-O-acetyl-2-deoxy-D-glucose 2,4DNFH 43.3 14.7 8. 2,4,5,6-tetra-O-acetyl-3-deoxy-D-glucose 2,4DNFH 38.3 17,0 _y 9. 2,3,4,5-tetra-O-acetyl-6-deoxy-D-glucose 2.4DNFH 35.8 +7.0 10. 2,4,5,6-tetra-O-acetyl-3-deoxy-D-mannose 2,4DNFH 52.7 10.7 11. 2,3,5,6-Tetra-O-acetyl-4-desolxy-Di; - mannose 2.4DNFH (prepared from 7) 47.9 24.8 12. 2,3,4,5-tetra-O-acetyl-6-deoxy-D-mannose 2.4DNFH 53.8. + 11.2 Acetylation of 2,4-dinitrophenyl hydrazones deoxysaccharides To 50 mg of 2,4 dinitrophenyl hydrazone (DNF) of the corresponding deoxysaccharide is added 0.5 ml of pyridine and 0.25 ml of acetic anhydride. The reaction mixture was cooled to 0 ° C with occasional shaking and the hydrazone was dissolved. Then the reaction mixture is left at 0 ° C yet After completion of the reaction, the reaction mixture is concentrated (below 40 ° C), to the residue is added 2 ml of ethanol - C 2 H ⁵ OH, from which ¹ the acetylderivative of the corresponding hydrazone is crystallized. ethanol yielding pure acetylderivative, yield about 75%.

h. The reaction is monitored by chromatography.

Claims (1)

Process for preparing acetylderivatives of 2,4-dinitrophenylhydrazones deoxysaccharides. with the antitumor effect, characterized in that the corresponding 2,4 dinitrophenylhydrazone deoxy of the invention is acetylated with acetic anhydride under the catalytic action of pyridines at 0 ° C.