Verfahren zur Herstellung von (Androst-17ss-yl)-alpha-pyronen

摘要

1,236,822. Butadienolides. FARBWEBKE HOECHST A.G. 17 June, 1968 [16 June, 1967; 25 Aug., 1967], No. 28682/68. Heading C2U. Compounds of formula (wherein Y is a free, ketalized or thioketalized oxo group, a hydrogen atom and a free or etherified or esterified hydroxyl group, or a #2-, #3- or #3,5-enolether, -enolester or -enamino grouping, and wherein there is optionally present one or more features selected from: #4, #5, #9(11), A11 and #14-unsaturation, a 4-, 6- or 15-free, etherified or esterified hydroxyl group and a 15-free or ketalized oxo group, and wherein any hydrogen atoms present in the 5- and 14-positions may have the α- or #-configuration), which compounds are claimed per se when they contain at least one carboncarbon double bond in addition to the double bonds in the pyrone ring, are prepared from 21-acetalized 20,21-dioxo steroids, wherein any oxo group in the 3- or 15-position is protected, by the routes shown in the following reaction scheme: wherein R 1 is alkyl, aryl or alkylaryl, R 3 is C 1-4 alkyl and Hal is Cl, Br or I. The reactants used are: (a) [Ph 3 PCH 2 OR 1 ]Hal in the presence of an anhydrous base in an inert organic solvent: (b) selective hydrolysis; (c) (R 2 O) 2 - P(O)CH 2 COOR 3 , wherein R 2 and R 3 are each C 1-4 alkyl, in the presence of an anhydrous base in an inert organic solvent; (d) acid or alkali; (e) acid or alkali; (f) acid; (g) Me 3 S+ - Hal- or Me 3 SO+Hal- (Hal = Cl, Br or I) in the presence of an anhydrous base in an inert organic solvent; (h) hydrohalic acid; (i) base; (j) either (R 2 O) 2 P(O)CH 2 COOR 3 in the presence of an anhydrous base in an inert organic solvent or Ph 3 P = CH-COOR 3 ; (k) acid; (1), (m) and (n) acid or base. The final products are interconvertible by esterification, de-esterification, etherification, de-etherification, ketalization or deketalization. 3# - Tetrahydropyranyloxy - 21,21 - dimethoxy- 5-pregnen-20-one is prepared from the free 3#-ol by reaction with dihydropyran. 3 - Ethoxy - 21,21 - dimethoxy - 3,5,14 - pregnatrien-20-one is prepared from 21-acetoxy- 4,14 - pregnadiene - 3,20 - dione via 21- hydroxy - 4,14 - pregnadiene - 3,20 - dione, 3,20 - dioxo - 4,14 - pregnadien 21 - al and 21,21 - dimethoxy - 4,14 - pregnadiene - 3,20- dione. Scillarenin is prepared by reduction of scillarenone, the latter being prepared by hydration of 14-anhydro-scillarenone. The compounds of Formula (I) are stated to possess positive inotropic, diuretic and cardiovascular activities and may be made up with carriers into pharmaceutical compositions for oral and parenteral administration.