Patent GB-1440361-A (GB)
Title: 11-deoxyprostaglandins of the e and f series and the preparation  thereof
IPC: C07C405/00
Filed: 1973-05-30
Abstract: 1440361 Prostaglandins AMERICAN CYANAMID CO 30 May 1973 [24 July 1972 17 Nov 1972] 25836/73 Heading C2C The invention comprises prostaglandins of the Formula A wherein R 1  is C 1-4  alkyl, C 2-4  (1-alkenyl), C 1-4  alkylthio, C 2-4  alkanoylthio, #-di(C 1-4  alkyl)- amino-C 1-4  alkylthio, cyano, carbamoyl, carboxy or C 2-4  alkoxycarbonyl, α-nitro-C 1-4  alkyl, αα - di(alkoxy - carbonyl) - C 1-4  alkyl, αα- dicarboxy - C 1-4  alkyl, α - carboxy - C 1-4  alkyl, S<SP>(+)</SP>(R 4 ) 3 X<SP>(-)</SP>, where R 4  is C 1-4  alkyl and X is halogen, p-toluenesulphonyloxy or C 1-4  alkylsulphonyloxy, formyl, αα-di(C 1-4  alkoxy)methyl, or mercapto; R 2  is hydroxy, C 1-4  alkanoyloxy, C 1-4  alkylsulphonyloxy, or C 1-4  alkyl, with the proviso that when R 2  is C 1-4  alkyl then R 1  is the same C 1-4  alkyl group; R 3  is H or C 1-12  alkyl; Y is >C=O, with the proviso that when Y is carbonyl then R 1  is not mercapto; the radical -C 5 -C 6 - is ethylene or cis-vinylene, and the radical -C 13 -C 14 - is ethylene or trans-vinylene, with the proviso that when -C 5 -C 6 - is cis-vinylene then -C 13 -C 14 - must be trans-vinylene, and phamaceutically acceptable salts thereof when R 3  is H. The compounds of Formula A in which R 2  is hydroxy or C 1-4  alkyl and R 1  is as defined above except than R 1  cannot be mercapto are prepared by reacting compounds of the formula wherein Z is H or acetyl with (R 4 ) 2 CuLi, R 6 CH(CO 2 R 7 ) 2 , R 6 CH 2 NO 2 , R 5 SH or acetone cyanohydrin in the presence of alkaline catalysts, where R 4  is C 1-4  alkyl, C 2-4  (1-alkenyl), R 5  is #-di(C 1-4  alkylamino)alkyl, C 1-4  alkyl, or C 1-4  alkanoyl, R 6  is H or C 1-4  alkyl, and R 7  is C 1-4  alkyl and when necessary or desired, hydrolysing, and, if desired decarboxylating the resulting compounds in which R 1  is α,α-di(alkoxycarbonyl)alkyl, or converting compounds in which R 1  is C 1-4  alkylthio, into compounds in which R 1  is S<SP>(+)</SP>(R 4 ) 2 X<SP>(-)</SP> by reacting them with alkyl halides alkyl p-toluene-sulphonates or alkyl alkylsulphonates, and when necessary or desired hydrolysing compounds in which R 1  is cyano to give compounds in which R 1  is carbamoyl, which in turn may be hydrolysed to give compounds in which R 1  is carboxy and then, if desired, esterified, and when necessary converting compounds in which R 1  is nitromethyl to the corresponding compounds in which R 1  is formyl and when necessary converting these compounds into compounds in which R 1  is dialkoxymethyl, and if desired reducing the carbonyl group in the resulting compounds, and when R 2  is hydroxy inverting its configuration and if desired hydrogenating the double bonds. Compounds of Formula A above in which R 1  is mercapto and Y is are obtained by reducing the corresponding compounds in which R 1  is alkanoylthio and Y is carbonyl with lithium perhydro-9b-boraphenalyl hydride. 15 - o - Acetytprostaglandin A 2  methyl ester is obtained by extracting it from Plexaura Homomalla (esper) with isomeric hexanes. Pharmaceutical compositions contain the above prostaglandins and pharmaceutically acceptable carriers. The compounds possess similar pharmacological properties to those of naturally occurring prostaglandins. Reference has been directed by the Comptroller to Specifications 1,097,533 and 1,097,157.