GB1316847A - Propadienyl steroids - Google Patents

Abstract

1316847 17α-Propadienyl steroids; lithium dialkyl copper solutions SYNTEX CORP 18 Aug 1970 [11 June 1970] 39751/70 Headings C2J and C2U Steroids having in the 17α-position the group -C(R<SP>1</SP>)=C=C.R<SP>2</SP>.R<SP>3</SP>, particularly those of the formulµ (wherein R<SP>1</SP> is C 1-4 alkyl; each of R<SP>2</SP> and R<SP>3</SP> is H or C 1-4 alkyl; R<SP>4</SP> is H or C 1-3 alkyl; R<SP>5</SP> is OH or an ester or ether thereof; R<SP>6</SP> is oxo or R<SP>8</SP>(α-H), where R<SP>8</SP> is H or OH or an ester or ether thereof; R<SP>7</SP> is H or CH 3 ; and R<SP>9</SP> is C 1-8 alkoxy, cycloalkoxy or OH or an ester or ether thereof, of which the 6,6-difluoro compounds are novel, are prepared by reacting 17α-(C=CC.R<SP>2</SP>.R<SP>3</SP>.R)-steroids, wherein R is halo or hydroxy or an ester or ether thereof with a lithium dialkyl copper reagent Li(R<SP>1</SP>) 2 Cu, preferably in an organic solvent at about - 20‹ to 50‹ C. Substituents which may compete or interfere with the reaction, e.g. 3-oxo groups, which are reduced to 3#-hydroxy groups, may be protected and subsequently released. Resulting 17-ols may be acylated or etherified. 17α - (3,3 - Dialkyl - 3 - hydroxypropynyl)- steroids are prepared from alkyl lithiums and 17α-carboxyethynyl-steroids, in turn prepared from 17α-ethynyl steroids as their Grignard derivatives and CO 2 . 17α-(3-Alkyl-3-hydroxypropynyl)-steroids are prepared by oxidizing 17α - (3 - hydroxypropynyl) - steroids to 17α- formylethynyl-steroids and reacting these with alkyl lithiums. In these products and in the 17α - (3 - hydroxypropynyl) - steroids the hydroxy group may be esterified or etherified or replaced by a halogen atom by standard procedures. 6,6 - Difluoro - 17α - (3 - acetoxypropynyl)-17#- tetrahydropyran - 2<SP>1</SP> - yloxyestr - 4 - en - 3 - one is prepared by oxidizing 3,3-ethylenedioxy-6,6- difluoroestr - 4 - en - 17# - ol (prepared from the 3-one and ethyleneglycol) to the 17-one, converting this by the procedure described in Specification 1,310,611 to 3,3-ethylenedioxy-6,6-difluoro- 17α - (3 - tetrahydropyran - 2<SP>1</SP> - yloxypropynyl)- estr-4-en-17#-ol, hydrolysing this to 6,6-difluoro- 17α - (3 - hydroxypropynyl) - estr - 4 - en - 17#-ol- 3-one and acetylating and etherifying this. Other acylates and ethers are prepared similarly. Lithium dialkyl copper solutions are prepared by adding alkyl lithiums to cuprous iodide in ether at ice-bath temperatures and under nitrogen. The novel 6,6-difluoro-steroids are stated to possess progestational and pituitary-inhibiting activity and they may be made up into pharmaceutical compositions with suitable carriers.