Patent GB-1273024-A (GB)
Title: 07alpha-ALKADIENYL STEROIDS
Inventor: GALANTAY EUGENE ERVIN
IPC: A23K1/165
Filed: 1969-04-02
Abstract: 1,273,024. 17α-Alkadienyl steroids. SANDOZ Ltd. 2 April, 1969 [10 April, 1968; 12 Sept., 1968], No. 17366/69. Heading C2U. The invention comprises d-steroids of formula wherein R<SP>1</SP> and R<SP>3</SP> are each C 1-3  alkyl ; R<SP>2</SP> is H, Me or C 2-4  alkanoyl; R<SP>4</SP> is H, OH or C 2-4  alkanoyloxy; and Z, embracing rings A and B and the substituents thereon, represents of of the groups Z1 to Z9 wherein R 5  is H, C 1-3  alkyl, C 5-7  cycloalkyl or C2-4 alkanoyl; R 6  is H, 6α-Me or 7α-Me; R 7  is H or Me; and R 8  is H, F, Cl or Me; with the provisos that (i) when Z represents Z1 in which R 6  is H and R 5  is H or C2-4 alkanoyl, then R 4  is H and/or R 2  is Me; and (ii) when Z is Z4 in which R 6  and R 7  are both H, R 4  is H and R 3  is Me, then R 1  is C 2-3  alkyl. Preparation of compounds of Formula I is from the corresponding 17-ones by reaction with an appropriate organometallic reagent to introduce the desired 17a-(1-alkylpropadienyl group or a 17α-(1-alkyl-2-propynyl) group, the latter group then being subjected to basic isomerization. Preferably any 3-hydroxy or 3-oxo group is protected during the organometallic reaction. Also, the 17#-hydroxy group should be protected during the basic isomerization. Compounds I may be prepared as racemates which must then be resolved to give the required disomers. Specific intermediates obtained in these processes are detailed below. Interconversions of compounds of Formula I are: (i) esterification of 3/16α/17#-hydroxy groups; (ii) methylation of a 17#-hydroxy group; (iii) reduction of a 3-oxo group to #- hydroxy; and (iv) isomerization of 3-oxo-#<SP>5(10</SP>) to 3-oxo-#<SP>4</SP>. Intermediates.-3 - methoxy - 17α- (2-butynyl). estra - 2,5(10) - dien - 17# - ol and 3 - methoxy- 17α - (1 - methylpropadienyl) - estra - 2,5(10)- dien - 17#. ol are prepared from the corresponding 17-one by reaction with Mg and 2- butynyl bromide (Example 1). 3 - Methoxy - 17α - (2 - butynyl)estra - 1,3,5(10)- trien - 17# - ol is obtained as a by-product in the conversion of the corresponding 17-one to the inventive 17α-(1-methylpropadienyl)-17#-ol (Example 2). dl - 3,17# - Diacetoxy - 17α - (1 - methylpropadienyl) - 13# - ethyl - gona - 1,3,5(10)- triene (XXI) is prepared from dl-13-homoestrone 3-tetrahydropyranyl ether (XX) by the sequence: XX # dl - 3 - tetrahydropyranyloxy - 17α - (1 - methyl - 2 - propynyl) - 13#- ethylgona - 1,3,5(10) - trien - 17# - ol # dl- 3,17# - bis - (tetrahydropyranyloxy)- 17α - (1- methyl - 2 -propynyl) - 13# - ethylgona - 1,3,5(10)- triene # dl - 3,17# - bis - (tetrahydropyranyloxy) - 17α - (1 - methylpropadienyl) - 13# - ethylgona - 1,3,5(10) - triene # dl - 3,17# - dihydroxy - 17α - (1 - methylpropadienyl) - 13#- ethylgona - 1,3,5(10) - triene # XXI (Example 7). 3,17# - Dimethoxy - 7α - methyl - 17α - (1- methylpropadienyl)estra- 2,5(10) - diene (XXIII) is prepared from 3-methoxy-7α-methylestra- 2,5(10)-dien-17-one (XXII) by the sequence XXII # 3 - methoxy - 7α - methyl - 17α- (1 - methyl - 2 - propynyl) - 17# - hydroxyestra- 2,5(10) - diene # 3,17# - dimethoxy - 7α- methyl - 17α - (1 - methyl - 2 - propynyl)estra- 2,5(10) - diene # XXIII (Example 8). Compounds of Formula I are said to possess progestational, estrogenic and deciduogenic activities, and may be made up with carriers into pharmaceutical compositions for oral and parenteral administration.