Patent GB-1310611-A (GB)
Title: Propadienyl steroids and method for their production
IPC: A61K31/567
Filed: 1970-04-14
Abstract: 1310611 17α-Propadienyl steroids SYNTEX CORP 14 April 1970 [18 April 1969 17 Nov 1969] 17675/70 Headings C2C and C2U Steroids of the formulae wherein R<SP>1</SP> is H or C 1-3  alkyl; R<SP>2</SP> is H, tetrahydrofuran-2-yl, tetrahydropyran-2-yl, 4-methoxy-tetrahydropyran-4-yl or carboxylic acyl R<SP>3</SP> is O or α-H(#-OR<SP>6</SP>) in which R<SP>6</SP> is H, acyl or an etherifying group as defined for R<SP>2</SP>; R<SP>4</SP> is H or CH 3 ; and R<SP>5</SP> is H, alkyl, cycloalkyl or another etherifying group as defined for R<SP>2</SP>, or acyl, of which the 4,9(10),11-estratrienes are novel, are prepared by treating 17α-C#C.CH 2 R steroids wherein R is OH, halo, tetrahydrofuran- 2-yloxy, tetrahydropyran-2-yloxy, 4-methoxytetrahydropyran-4-yloxy or optionally substituted alkyl- or aryl-sulphonyloxy with an aluminium hydride reagent. Resulting products (which may contain a ketalized 3-oxo group) may be oxidized and reduced at the 3-position and esterified, etherified and hydrolysed by standard procedures. Starting materials.-17α-C#C.CH 2 R steroids as defined above are prepared (i) when R is etherified OH, by treating the corresponding 17-oxo-steroid with the Grignard reagent prepared from appropriate propargyl ethers and ethyl magnesium bromide; (ii) when R is OH, by hydrolysis of the products of (i), or by reacting the corresponding 17α-ethynyl steroids (in which R<SP>2</SP> is preferably an etherifying group) as their Li salts with paraformaldehyde; (iii) when R is halo, by halogenation of the products of (ii) with SOCl 2 , SOBr 2 , PCl 5 , PBr 5  or hydrocarbon sulphonyl fluorides; or (iv) when R is alkyl- or aryl-sulphonyloxy, by esterification of the products of (ii). The products and intermediates may be subjected to standard etherifications, esterifications, hydrolyses and reductions. These starting materials may possess a ring structure which is converted into one of the abovedepicted structures in the course of the processes involved, e.g. they may be 3-ethoxy-estra-3,5- dienes. 3 - Ethoxy - estra - 3,5 - dien - 17 - one is prepared by enol etherification of estr-4-ene- 3,17 - dione. 3 - Methoxy - 17α - ethynyl - 17#- tetrahydropyran - 2<SP>1 </SP>- yloxyestra - 1,3,5(10) - triene is prepared by etherification of the corresponding 17# - ol. 3# - Acyloxy - 6,6 - difluoroestr - 4- ene - 17 - ones, corresponding androstane compounds, and their 18-homologues are prepared from 3-ethoxy estr-3,5-dien-17-one and appropriate homologues via 3-ethoxy-6-fluoroestra-3,5- dien - 17 - one, 6,6 - difluoroestr - 4 - ene - 3,17- dione, and 6,6 - difluoroestr - 4 - ene - 3#,17#- diol and its di-ester and mono-esters and their homologues. 3-Ethers may be prepared similarly. 3# - Acyloxy - estra - 4,9(10),11 - trien - 17 - ones and their 18-homologues are prepared from 17#- acetoxyestr-4-en-3-one and its homologues via 3,3 - ethylenedioxy - 17# - acetoxy - estr - 5(10)- ene, 17# - acetoxyestr - 5(10) - en - 3 - one, 17#- acetoxyestra - 4,9(10) - dien - 3 - one, estra- 4,9(10) - dien - 17# - ol - 3 - one, estra - 4,9(10)- diene - 3,17 - dione, 3,3; 17,17 - bisethylenedioxyestra - 5(10),9(11) - diene, estra - 4,9(10),11- triene - 3,17 - dione, estra - 4,9(10),11 - triene- 3#,17# - diol and 3# - acyloxyestra - 4,9(10),11- trien - 17# - ols and their homologues. Intermediate 17-ones in these processes may be converted to 17α-ethynyl-17#-ols which may then be etherified. 3 - Tetrahydropyran - 2<SP>1</SP> -  yloxypropyne, 3- tetrahydrofuran - 2<SP>1</SP> - yloxypropyne and 3-(4<SP>1</SP>- methoxytetrahydropyran - 4<SP>1 </SP>- yloxy) - propyne are prepared from propargyl alcohol and, respectively, dihydropyran, dihydrofuran and 4-methoxy-5,6-dihydro-2H-pyran. The steroids of the above general formulae variously possess estrogenic, anti-androgenic, progestational, pituitary-inhibiting and antifertility activity, and they may be made up into pharmaceutical compositions with suitable carriers. Specifications 1,304,395 and 1,310,612 are referred to.