Patent GB-922316-A (GB)
Title: New d-homo-etiocholane derivatives and processes for their preparation and conversion
IPC: C07J75/00
Filed: 1959-09-01
Abstract: The invention comprises 3a ,17-dihydroxy-11-keto-18-nor-D-homoetiochola-12,17(17a)-diene of the formula <FORM:0922316/IV(a)/1> 3a -hydroxy-11,17-diketo- 18-nor-D-homo-13a -etiocholane of the formula <FORM:0922316/IV(a)/2> 3a -hydroxy-11-keto- 17-ethylenedioxy-18-nor-D-homo-13a  -etiocholane of the formula <FORM:0922316/IV(a)/3> 3a ,11b - dihydroxy- 17-keto-18-nor- D-homo-13a -etiocholane of the formula <FORM:0922316/IV(a)/4> 3a ,17- diacetoxy- 11-keto- 18-nor- D-homo-etiochola-12,17(17a) -diene of the formula <FORM:0922316/IV(a)/5> 3a -acetoxy- 11-keto- 17-hydroxy- 18-nor-D-homoetiochola- 12, 17(17a)-diene of the formula <FORM:0922316/IV(a)/6> 3a -acetoxy- 11-keto- 17b -hydroxy- 18-nor-D-homo-13a -etiocholane of the formula <FORM:0922316/IV(a)/7> 3a -acetoxy- 11,17-diketo-18-nor- D-homo-13a -etiocholane of the formula <FORM:0922316/IV(a)/8> 3a -acetoxy- 11-keto- 17-ethylenedioxy-18-nor-D-homo-13a  -etiocholane of the formula <FORM:0922316/IV(a)/9> 3a , 11b -dihydroxy-17-keto- 17a-hydroxymethyllene-18-nor- D-homo-13a  -etiocholane of the formula <FORM:0922316/IV(a)/100> and 3a ,11b -diacetoxy-17-keto-18-nor-D-homo-13a -etiocholane of the formula <FORM:0922316/IV(a)/111> and processes comprising each stage and the whole of the following synthesis:-The compound of the first formula above is prepared by cyclising a lower alkyl ester of 3a -hydroxy-11- keto-13,17-seco-etiochol-12-en-17-oic acid of the formula <FORM:0922316/IV(a)/122> (this reactant may optionally be prepared by esterifying the corresponding free acid), the product is then treated in either of the following ways to form a compound of the fourth formula above (1) the compound of the second formula above is obtained by hydrogenating the said product; the compound of the third formula above is prepared by ketalising the compound of the second formula; and the compound of the fourth formula above is prepared by simultaneously liberating the 17-keto group by acid treatment and reducing the 11-keto group with an alkali metal borohydride; or (2) the diester compound of the fifth formula above is obtained by esterifying the said product; the monoester compound of the sixth formula above is prepared by selectively saponifying the diester; the compound of the seventh formula above is obtained by hydrogenating the monoester; the compound of the eighth formula above is prepared by oxidising the hydrogenated product from the previous step; the compound of the ninth formula above is prepared by ketalising the product of the previous step; and the compound of the fourth formula above is prepared by reducing the previous product with an alkali metal borohydride and liberating the 3a -hydroxy group and 17-keto group by acid hydrolysis; the compound of the fourth formula above is then treated in either of the following ways to form the 18-11 lactone of 3a ,11b -dihydroxy- 13,17-secoetiocholan-17,18-dioic acid, the free acid having the formula <FORM:0922316/IV(a)/133> (1) reaction with the sodium derivative of a lower alkyl formate to form a compound of the tenth formula above and reaction of this product with hydrogen peroxide; or (2) esterification to form the diester of the eleventh formula above, lactonisation of the diester with an organic per-acid to form the 17-18 lactone of 3a ,11b -diacetoxy-18-hydroxy-13a ,17-seco-13a -etiocholan-17-oic acid of the formula <FORM:0922316/IV(a)/144> oxidation of this compound to form 3a ,11b -diacetoxy- 3-17-secoetiocholan- 17,18-dioic acid of the formula <FORM:0922316/IV(a)/155> and saponification of this product with warm alkali and then acid; and the resulting 18-11 lactone of 3a ,11b -dihydroxy-13,17-seco-etiocholan-17,18-dioic acid may be subjected to oxidation to form the corresponding 3-keto compound.