STARTING COMPOUNDS FOR PREPARING CALCITRIOL AND ITS DERIVATIVES, METHOD FOR PREPARING THESE STARTING COMPOUNDS AND INTERMEDIATE PRODUCTS FOR THIS METHOD

摘要

Starting compounds for preparing calcitriol (1 alpha , 25-dihydroxycholecalciferol) and its derivatives showing, as compared with calcitriol, some modifications, particularly in the C-17 lateral chain, a method for preparing these starting compounds and intermediate products for this method are described. The new compounds have the general formula (I), wherein R<1> stands for a hydrogen atom, an alkyl, silyl, acyl, aryl, alkoxycarbonyl or alkoxyalkyl group whose meaning is more closely defined in the description and either a) A stands for a methylene group and R the residue -(CH2)n-CH2-CR<2>R<3>OH (n = 1, 2, 3, 4, 5, 6, 7), wherein R<2> and R<3> stand independently for a hydrogen atom, a C1-4 alkyl group or R<2> and R<3> stand for a cyclopropyl to cyclohexyl ring or b) A stands for a direct bond and R a carbaldehyde residue. The new compounds are prepared from the known compound (20S)-20-hydroxymethyl-1,1-4-pregnadien-3-one by isomerization to the 1,5-dien-3-one and then, in case a) conversion of the 20-hydroxymethyl group to a 20-sulfonyloxymethyl group, reduction of the 3-keto group to the hydroxy group, construction of the side chain, oxidation to the 7-keto compound, epoxidation in the 1,2 position, conversion of the 7-ketone to the corresponding tosylhydrazide and reduction of the 7-tosylhydrazide with lithium aluminium hydride. In case b), the 20-hydroxymethyl group is protected by a protective group which is readily split off, the 5,7-diene is prepared as in a), the protective group is split off and the 20-hydroxymethyl compound is oxidized to the corresponding aldehyde.