FI48074B

1319372 22-Substituted cardenolide glycosides DR KARL THOMAE GmbH 13 Jan 1971 [14 Jan 1970] 1686/71 Heading C2U The invention comprises compounds of formula wherein X is F or Me; R 1 and R 2 and R 3 are each H or identical lower acyl groups, or R 1 is H or lower acyl and R 2 and R 3 together represent isopropylidene; and either R 4 is Me and R 5 is H, or R 4 is CHO or CH 2 OH and R 5 is OH. Synthesis (a): base-induced intramolecular cyclization of compounds of formula (wherein R1 1 , R1 2 and R1 3 are protecting groups, R 6 is C 1-3 alkyl, and either R1 4 is Me and R1 5 is H or R1 4 is protected CH 2 OH and R1 5 is OH) followed, where necessary by removal of protecting groups. Synthesis (b): reaction of compounds of formula III with compounds of formula IV (wherein R 4 is as defined above with the exclusion of CH 2 OH, and Ac is acyl (e.g. acetyl or benzoyl)), followed where appropriate by removing of the acyl groups. The reaction is preferably effected in the presence of mercuric cyanide. Interconversions of compounds I disclosed are: (a) esterification and de-esterification in the sugar moiety; (b) 21,31-acetonization; and (c) reduction of 19-oxo to 19-hydroxy. Compounds II are prepared from the corresponding 21-ols by reaction with HO-COCH(X)-P(O)(OR 6 ) 2 . Compounds III are prepared from 3#-acyloxy- 14#, 21-dihydroxy-5#-pregnan-20-one or 3#,19- diacyloxy-5#, 14#, 21-trihydroxypregnan-20- one by the successive steps of: (i) reaction with HO-CO-CH(X)-P(O)(OR 6 ) 2 to introduce the corresponding 21-ester group, (ii) base-induced intramolecular cyclization to form the butenolide ring, (iii) hydrolysis of the 3-acyloxy group and of any 19-acyloxy group, and (iv) oxidation of any 19-hydroxy group to OXO. Pharmaceutical compositions for oral, rectal or parenteral administration comprise a cardioactive compound of Formula I and a carrier.