Patent GB-1453889-A (GB)
Title: Prostaglandins and processes for their productionp
IPC: C07C405/00
Filed: 1974-11-11
Abstract: 1453889 Prostaglandins UPJOHN CO 11 Nov 1974 [12 Nov 1973] 48756/74 Heading C2C The invention comprises a process for preparing optically active prostaglandins of the Formula I and racemates thereof, wherein m is oxo or wherein R 2  is H or C 1-4  alkyl; R is H, C 1-12  alkyl, C 3-10  cycloalkyl, C 7-12  aralkyl or phenyl optionally substituted 1 to 3 times by chlorine and/or C 1-4  alkyl; and R 1  is or  in which R 3  and R 4  each are H, F or C 1-4  alkyl, with the proviso that -C(R 3 )R 4 - is not -CF.alkyl-, n is 1 to 5, CmH 2 m is a valence bond or C 1-12  alkylene, with 1 to 6 carbon atoms in the chain between -CH 2 - and the ring, T is C 1-4  alkyl, C 1-4  alkoxy, CF 3 , OH, F or Cl, and s is 0 to 3, provided that when s is 2 or 3 the T's may be the same or different and not more than two T's are other than alkyl; and the novel prostaglandins of Formula I above and optically active compounds of Formulµ VII and VIII and racemates thereof, wherein E 1  is or wherein R 5  is 2-tetrahydropyranyl, 2-tetrahydrofuranyl, or a group of the formula in which R 6  is C 1-18  alkyl, C 3-10  cycloalkyl, C 7-12  aralkyl or phenyl optionally substituted by 1 to 3 C 1-4  alkyl radicals; either R 7  and R 8  are each H, C 1-4  alkyl or phenyl optionally substituted by 1 to 3 C 1-4  alkyl radicals, or R 7  and R 8  are taken together and are -(CH 2 ) a - or -(CH 2 ) b -O-(CH 2 ) c  in which a is 3, 4 or 5, b is 1, 2 or 3 and c is 1, 2 or 3 with the proviso that b plus c is 2, 3 or 4; and R 9  is H or phenyl. The compounds of Formula I are novel provided that when (a) m is R 1  is not n-pentyl; (b) when m is oxo, R 2  is C 1-4  alkyl; or (c) when m is oxo and R 2  is H, R 1  is n-propyl CH 2 -CmH 2 m-Ph(T) s  or C(R 10 )R 11 (CH 2 ) n CH 3  in which R 10  is H, F or C 1-4  alkyl and R 11  is F or C 1-4  alkyl, with the proviso that -C(R 10 )R 11  is not -CF alkyl. Compounds of Formula I above in which E is and R 2  is H are prepared by reacting lactols of the formula with (4 - carboxybutyl)triphenylphosphonium bromide and sodium methylsulphinylmethylide, and hydrolysing the compounds VII above in which R is H so obtained to remove blocking group R 5 , and optionally esterifying the compound thus obtained either before or after the removal of the blocking group R 5 . Compounds of Formula I in what m is oxo and R 2  is H are obtained by oxidizing compounds of Formula VII above and hydrolysing the compounds of Formula VIII thus obtained to remove the blocking group R 5 , and optionally esterifying the compounds obtained in which R is H either before or after the removal of the blocking group R 5 . Compounds of Formula I above in which R 2  is C 1-4  alkyl are prepared in a similar manner from lactols of the formula in which E 3  is or where R 12  is C 1-4  alkyl. Pharmaceutical compositions, suitable for oral, parenteral or rectal administration or by inhalation, contain the above prostaglandins or salts thereof and pharmaceutically acceptable solid or sterile liquid carrier. The compounds possess similar pharmacological properties to p-prostaglandins A, B, E and F.