Patent GB-1332262-A (GB)
Title: Prostaglandins and the preparation thereof
IPC: C07C405/00
Filed: 1971-08-17
Abstract: 1332262 Prostaglandins UPJOHN CO 17 Aug 1971 [11 Sept 1970 (2)] 38572/71 Heading C2C [Also in Divisions A5 and C3] The invention comprises novel prostaglandins of the formulae wherein Q is one of the four carbocyclic radicals of the formula J is H # OCOCH 3 , R 9  is H or acetyl; and R 11  is HCH 3 ; D is one of the carbocyclic radicals wherein Y is = O, H # OH or H #  OH, X is H # OH or H # OH when D is radical (e); X is =O when D is radical (f); and X is H #  OH when D is radical (g); and R 1  is H, C 1-8  alkyl, C 3-10  cycloalkyl, C 7-12  aralkyl, phenyl optionally substituted by 1 to 3 C 1  or C 1-4  alkyl; with the proviso that when D is radical (g) and Y is = O, R 1  is not N or CH 3 , and salts thereof when R 1  is H; 15#-PGE 2 , its methylester, 15#- PGE 2  15-acetate methyl ester, methyl PGE 2  15- acetate, methyl PGF 2 α 15-acetate and methyl PGF 2 # 15-acetate, and processes from preparing PGF 2 α and PGE 2 . The process for preparing PGF 2 α comprises (1) reducing a mixture of the alpha and beta 10,11-epoxide of 15#-PGA 2  acetate methyl ester to a mixture of 15#-PGE 2  and 11#,15#-PGE 2  15-acetate methyl esters, (2) separating the 15#-PGE 2  15-acetate methyl ester from the 11#,15#-PGE 2  15-acetate methyl ester, (3) silylating said 15#-PGE 2  15-acetate methyl ester to give 15#-PGE 2  11-O-Si-(A) 3  ether 15-acetate methyl ester (where A is C 1-4  alkyl, C 7-12  aralkyl, phenyl optionally substituted with 1 or 2 F, Cl or C 1-4  alkyl), (4) reducing the product of step 3, and then hydrolysing the resulting product to give a mixture of 15#- PGF 2 α and PGF 2 # 15-acetate methyl esters, (5) separating the 15#-PGF 2 α 15-acetate methyl ester from the 15#-PGF 2 # 15-acetate methyl ester, (6) saponifying the 15#-PGF 2 # 15-acetate methyl ester, (7) oxidizing the 15#-PGF 2 α to give 15-oxo-PGF 2 α, (8) silylating the 15-oxo- PGF 2 α to give 15-oxo-PGF 2 α 9,11-di-Si(A) 3  ether or the Si(A) 3  ester of that ether, (9) reducing the product of step 8 and then hydrolysing the resulting product to give a mixture of PGF 2 α and 15#-PGF 2 α and (10) separating the PGF 2 α from the 15#-PGF 2 α. PGE 2  is obtained by reducing a mixture of the alpha and beta 10,11-epoxides of PGA 2 -15-Si(A) 3  ether and then hydrolysing the resulting product and separating the resulting mixture of PGE 2  and 11#-PGE 2 . 15#-PGE 2 , 15#-PGE 2  15-acetate, 15#-PGE 2  methyl ester and 15#-PGE 2  15-acetate methyl ester are obtained by extracting colonies of the marine invertebrate Plexaura homomalla (Esper.), 1792, forma R. Compounds of the formula   wherein R<SP>2</SP> is H or CH 3  and G is H # OR 5  or H # OR 5  wherein R 5  is H or COCH 3  are obtained by contacting the corresponding alpha and beta 10,11-epoxides with reductive epoxide opening agents such as chromium (11) salts of aluminium and water. Carbonyl reduction of the compounds thus obtained gives the corresponding PGF 2  compounds, which may also be obtained by prolonged treatment of the alpha and beta 10,11-epoxides with the above mentioned reductive epoxide opening agents. Esters thus obtained may be hydrolysed and the resulting acids esterified. The 15-oxo compounds are prepared by ozidizing the corresponding 15- hydroxy compounds. PGE 2  and its methyl ester and PGE 2 -15- acetate methyl ester are obtained by extracting colonies of Plexaura homomalla (Esper.) 1792 forma S. PGE 2  and 5,6-trans-PGE 2  are separated from each other by chromatography through a column packed with a silver saturated ion exchange resin.