PROCEDE DE PREPARATION DE NOUVEAUX COMPOSES CYTOSTATIQUES ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT

摘要

The invention relates to novel cytostatic compounds of the general formula I <IMAGE> in which R<4> represents ss-hydroxyl and R<3> represents alpha -ethyl or R<4> represents hydrogen and R<3> represents ss-ethyl ( alpha and ss designate the spatial position), R'' denotes a straight-chain alkyl group having 1 or 3-10 carbon atoms, a branched alkyl group having 3-10 carbon atoms, where the carbon atom bonded to the -N-CH2-O- group is a primary or secondary carbon atom, or an arylalkyl group containing 1-3 carbon atoms in the alkyl moiety, and R<1> represents a methoxy group, and R<2> represents an acetyl group. The novel compounds have strong cytostatic properties and are less toxic by more than an order of magnitude than known compounds of similar structure and type of action. The compounds are prepared according to the invention by reacting a compound of the general formula II <IMAGE> in which the meaning of R<1>, R<2>, R<3> and R<4> is the same as above, with a large excess of an alcohol of the general formula III <IMAGE> in which the meaning of R'' is the same as above with the difference here that the carbon atom connecting to the OH group can only be primary or secondary, in the presence of chromium trioxide, a suitable organic solvent, acetic anhydride and an acid at temperatures between -60 and -30 DEG C, then adjusting the pH of the reaction mixture to 8-10, isolating the product and, if desired, purifying it.