18 OR 19 Hydroxy prostaglandins

摘要

Novel 18 -, 19 - and 20 -hydroxy-prostaglandin derivatives of the formula I (I) wherein the dotted line in the position 8-12 indicates the optional presence of a double bond, the waved lines in position 15 indicate that the hydroxyl group and the group R4 are either in alpha - or beta -position and Z represents a - CH2CH2 - or a cis - CH=CH - group, and wherein R represents one of the groups: (wherein the waved lines indicate that the hydroxyl groups are either in alpha - or beta -position and R1 represents a hydrogen atom, a methyl or ethyl group), R2 represents either an oxygen atom or a hydrogen atom and an alpha - or beta -hydroxyl group, R3 represents a hydrogen atom or a hydroxyl group and R4 represents a hydrogen atom or a methyl group, with the proviso that when simultaneously, R1, R3 and R4 each represents a hydrogen atom, R2 represents an oxygen atom, a double bond is in 8-12 position and the 15-hydroxyl group is in position alpha , R does not represent the group (b), but that when in addition to these conditions, Z represents a cis - CH=CH - group and the 8-12 position is saturated, R either represents the groups (b) or (c); and the pharmaceutically acceptable salts and esters thereof, novel process for their preparation by selective microbiological hydroxylation of compounds of formula II (II) wherein the dotted line in the position 10-11 indicates the optional presence of a double bond in case the 8-12 position is saturated and the other symbols are as defined hereinabove, by means of microorganisms of the Division of Eumycota or, as far as the introduction of a hydroxyl group in the 18- or 19-position is concerned, of the Family of Streptomycetaceae, and, if desired, conversion of the 18 -, 19 - and 20 -hydroxy-prostaglandin derivatives thus obtained into pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions containing at least one of the novel hydroxy-prostaglandin derivatives of formula I.