GB1499253A - Prostaglandins - Google Patents

Abstract

1499253 11-Deoxyprostaglandins UPJOHN CO 16 Jan 1976 [14 Feb 1975] 01696/76 Heading C2C The invention comprises 11-deoxyprostaglandins of the Formula I or mixtures comprise these compounds and the enantiomers thereof, wherein one of W 1 and W 2 is hydrogen and the other is hydroxy or W 1 and W 2 together are oxo; g is 3 to 5; n is 1 to 5; R 1 is H, C 1-12 alkyl, C 3-10 cycloalkyl, C 7-12 aralkyl, or phenyl optionally substituted 1 to 3 times by halogen atoms or C 1-4 alkyl radicals; M 1 is H H | | --- OCH 3 or -OCH 3 ; X is cis CH=CH or -CH 2 CH 2 and Y is trans - CH # CH- or -CH 2 CH 2 -; with the proviso that when W 1 and W 2 together are oxo, X is cis-CH=CH; and pharmaceutically acceptable salts thereof when R 1 is H; their preparation by known methods and processes for preparing 11-deoxyprostaglandins of the Formula I above in which OH OH (a) M 1 is -CH 3 or --- CH 3 , X is cis-CH = CH, Y is -CH 2 CH 2 - and R 1 , W 1 , W 2 , g and n are as defined above and (b) H H M 1 is --- OCH 3 or -OCH 3 ; X is -CH 2 CH 2 -, W 1 and W 2 together are oxo and R 1 , Y 1 , g and n are as defined above. The process for preparing the compounds defined in (b) above comprises hydrogenating the corresponding compounds in which X is cis-CH = CH and Y is CH 2 CH 2 with 1 molar equivalent of hydrogen or hydrogenating the corresponding compounds in which X is cis CH = CH and Y is trans-CH = CH with 2 molar equivalents of hydrogen. The processes for preparing compounds defined in (b) above are: (1) for those compounds in which W 1 is OH and W 2 is H, reducing the corresponding compounds in which W 1 and W 2 together are oxo and separating the 9#-hydroxy epimers from the 9α-hydroxy epimers; (2) for those compounds in which W 1 and W 2 together are oxo, oxidizing the corresponding compounds in which W 1 is H and W 2 is OH; and (3) for those compounds in which W 1 is H and W 2 is OH, (1) C-methylating lactones of the Formula A to convert the 3-oxo group to a group of the OH OH # forms -CH 3 or --- CH 3 , (2) catalytically hydrogenating the products thus obtained, reducing the products of step (2) to lactals, (4) reacting the products of step (3) with compounds of the formula (5) separating the C-15 epimers of the product and (6) optionally esterifying the products of step (5). The following intermediates are also prepared, the lactones of the Formula A above; lactones of the Formula XXIII wherein Y is trans-CH = CH- or -CH 2 CH 2 - and M 6 is wherein R 2 is H or 2-tetrahydropyranyl, and the corresponding lactols; lactones of the Formula XXIII above in which Y is trans OR 3 OR 3 # CH = CH and M 2 is -CH 3 or --- CH 3 , wherein R 3 is benzoyl; methyl 9-oxo-15-methyl-15- hydroxy - cis - 5, trans - 13 - prostadienoate and the 15-(2-tetrahydropyranyl) ether thereof, and methyl 9α-hydroxy-15-oxo-cis-5, trans-13 prostadienoate. Pharmaceutical compositions, suitable for oral, parenteral, intravaginal, rectal, buccal, sublingual and topical administration, contain the novel 11-deoxyprostaglandins or salts thereof together with pharmaceutically acceptable carriers. The compounds possess prostaglandinlike activities. Specifications 1,398,072 and 1,444,963 are referred to.