Patent GB-1476661-A (GB)
Title: Prostaglandins
IPC: C07D309/12
Filed: 1974-05-13
Abstract: 1476661 Prostaglandins AMERICAN CYANAMID CO 13 May 1974 21132/74 Headings C2C C2J and C2P [Also in Division C3] The invention comprises prostaglandins of the Formulae A and B wherein the side chains attached to the C 8  and C 12  positions of the cyclopentane, cyclopentene or cyclohexane ring are trans to each other and a hydroxy substituent at the C 11  position is trans to the side chain at the C 12  position; Y is Z is -(CH 2 ) m -, -(CH 2 ) m -C(R 4 ) 2 -CH 2 -, -(CH 2 ) m -CH(R 5 )-, -(CH 2 ) m -O-CH 2 -, cis-CH 2 -CH=CH-CH(R 6 )-(CH 2 ) p - or -(CH 2 ) m -S-CH 2 -, wherein m is 3 to 8, p is 1 to 5, R 4  is C 1-3  alkyl, R 5  is C 1-3  alkyl, F or phenyl, and R 6  is H or C 1-4  alkyl; -C 13 -C 14 - is ethylene or trans-vinylene; R 1  is C 1-3  alkyl; X is -CH 2 -, -CH 2 CH 2 - or Q is wherein R 7  is H or C 1-3  alkyl; R 3  is OH, C 1-12  alkoxy, 2-tetrahydropyranyloxy or trialkylsilyloxy; s is 0 to 5; t is 0 or 1; and R is C 5-9  cycloalkyl, C 5-9  cycloalkenyl, mono- or dialkyl substituted C 3-8  cyclo-alkyl or mono- or di-alkyl substituted C 5-8  cycloalkenyl; with the first proviso that when s and t are both 0 and -C 13 -C 14 - is trans-vinylene then R cannot be an optionally substituted cyclopropyl group; with the second proviso that when Z is -(CH 2 ) m - or and R is optionally substituted cycloalkyl then the sum of s and t is at least 1; and with the third proviso that when -C 13 -C 14 - is ethylene then Z cannot be and pharmaceutically acceptable salts thereof when R 3  is OH. The compounds are prepared by reacting cyclopentenones or cyclohexenones of the Formula H and R<SP>1</SP> 3  has all the values of R 3  except hydroxy, with alonates of the formula where R 9  is alkyl and R<SP>1</SP> 2  is triphenylmethyl or mono- or di-methoxy-substituted triphenylmethyl, to give compounds of the Formula J  followed by hydrolysing the ester and ester groups with weak acids, to give compounds of the Formula K  wherein R<SP>11</SP> 3  is OH or C 1-12  alkoxy, and optionally hydrolysing those compounds in which R 3 <SP>11</SP> is C 1-12  alkoxy; optionally hydrogenating the C 13 -C 44  double bonds; optionally dehydrating the resulting compounds in which X is to give compounds of the Formula B above, optionally reducing the 9-oxo groups, and optionally introducing a C 1-3  alkyl group at C 16  in a known manner. The following intermediates and starting materials were also prepared: cyclopentenones or cyclohexenones of Formula H above including compounds in which X<SP>1</SP> is 2 - (# - carboxy - 2 - cis - alkenyl) - 3,4 - epoxycyclopentanol; 2 - (# - carboxy - 2 - cis - alkenyl) - 3,4 - epoxycyclopentanone; alkenes of the formula wherein R<SP>11</SP> 2  is H, triphenylmethoxy or mono- or di-methoxy substituted triphenylmethoxy; methyl and ethyl 2-(2-methoxyethyl)-2-oxocyclopentanecarboxylates; 2 - (2 - methoxyethyl)cyclopentan - 1 - one; 1 - acetoxy - 2- (2 - methoxyethyl)cyclopent - 1 - ene; 2 - (2- hydroxyethyl) - 2 - cyclopenten - 1 - one; 2- formyl - methyl - 2 - cyclpenten - 1 - one; 2- oxa - 3 - hydroxybicyclo[3,3,0]oct - 6 - ene; 2 - bromo - 2 - (2 - methoxyethyl)cyclopentan- 1 - one; 2 - (# - carboxy - 2 - cis - alkenyl) - 3- cyclopenten - 1 - ols; 2 - (# - carboxy - 2 - cisalkenyl) - 3 - cyclpenten - 1 - ones; compounds of the Formula A above in which R 3  is OCH 3 , Y is and Q is Phosphonium bromides of the formula wherein A is C 3-7  alkylene, are prepared by reacting phosphine with the acids of the formula BrACOOH. Alanates of the formula wherein R 9  is alkyl and R<SP>1</SP> 2  is triphenylmethyl or mono- or di-methoxy substituted triphenylmethyl are prepared by reacting trialkyl aluminiums with (3-OR<SP>1</SP> 2 -1-trans-alkenyl) lithiums of the formula  obtained by reacting the corresponding S-OR<SP>1</SP> 2 - 1-halo-1-trams-alkenes with butyl lithium. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above prostaglandins and pharmaceutically acceptable carriers or diluents. The compounds are used as hypotensive agents.