Patent EP-0190759-B1 (EP)
IPC: C07J41/00
Filed: 1986-02-06
Granted: 1989-08-30
Abstract: 1. Claims (for Contracting States : BE, CH, DE, FR, GB, IT, LU, NL, SE) 13-alkyl-11 beta-phenyl-gonanes of general formula I   see diagramm : EP0190759,P23,F3   wherein A and B together represent an oxygen atom, a CH2 group or a second bond between carbon atoms 9 and 10, X represents an oxygen atom or the hydroxyimino grouping N apprch OH, R1 represents a straight-chained or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms that is to contain the grouping   see diagramm : EP0190759,P23,F4   with X having the meaning mentioned above, R2 represents a methyl or ethyl radical in the alpha- or beta-configuration, wherein, in the case of a methyl or ethyl radical in the alpha-configuration, R3 /R4 represents   see diagramm : EP0190759,P23,F5     see diagramm : EP0190759,P24,F1   or   see diagramm : EP0190759,P24,F2   and wherein, in the case of a methyl or ethyl radical R2 in the beta-configuration, R3 /R4 represents   see diagramm : EP0190759,P24,F3   with R5 representing a hydrogen atom or an acyl radical having from 1 to 4 carbon atoms, Y representing a hydrogen, chlorine, fluorine, iodine or bromine atom, or an alkyl, hydroxyalkyl, alkoxyalkyl or acyloxyalkyl group each having from 1 to 4 carbon atoms in the or each alkyl or acyl radical, R6 representing a hydrogen atom, a hydroxy group, or an alkyl, O-alkyl or O-acyl group each having from 1 to 4 carbon atoms, m representing 0, 1, 2 or 3, R7 representing a hydroxy or cyanide radical, or an O-alkyl or O-acyl group each having from 1 to 4 carbon atoms, and k representing 0, 1 or 2, R8 representing a hydrogen atom, or an alkyl or acyl group each having from 1 to 10 carbon atoms, R9 , R10 , R11 and R12 each represents a hydrogen atom, a hydroxy group, or an alkyl, alkoxy or acyloxy group each having from 1 to 4 carbon atoms, or a halogen atom, and the substituent of the 11 beta-phenyl radical is in the 3- or 4-position. 1. Claim (for Contracting State AT) Process for the manufacture of compounds of general formula I   see diagramm : EP0190759,P26,F4   wherein A and B together represent an oxygen atom, a CH2 group or a second bond between carbon atoms 9 and 10, X represents an oxygen atom or the hydroxyimino grouping N apprch OH, R1 represents a straight-chained or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms that is to contain the grouping   see diagramm : EP0190759,P27,F1   with X having the meaning mentioned above, R2 represents a methyl or ethyl radical in the alpha- or beta-configuration, wherein, in the case of a methyl or ethyl radical in the alpha-configuration, R3 /R4 represents   see diagramm : EP0190759,P27,F2   or   see diagramm : EP0190759,P27,F3   and wherein, in the case of a methyl or ethyl radical R2 in the beta-configuration, R3 /R4 represents   see diagramm : EP0190759,P27,F4     see diagramm : EP0190759,P28,F1   with R5 representing a hydrogen atom or an acyl radical having from 1 to 4 carbon atoms, Y representing a hydrogen, chlorine, fluorine, iodine or bromine atom, or an alkyl, hydroxyalkyl, alkoxyalkyl or acyloxyalkyl group each having from 1 to 4 carbon atoms in the or each alkyl or acyl radical, R6 representing a hydrogen atom, a hydroxy group, or an alkyl, O-alkyl or O-acyl group each having from 1 to 4 carbon atoms, m representing 0, 1, 2 or 3, R7 representing a hydroxy or cyanide radical, or an O-alkyl or O-acyl group each having from 1 to 4 carbon atoms, and k representing 0, 1 or 2, R8 representing a hydrogen atom, or an alkyl or acyl group each having from 1 to 10 carbon atoms, R9 , R10 , R11 and R12 each represents a hydrogen atom, a hydroxy group, or an alkyl, alkoxy or acyloxy group each having from 1 to 4 carbon atoms, or a halogen atom, and the substituent of the 11 beta-phenyl radical is in the 3- or 4-position, characterised in that a compound of general formula II   see diagramm : EP0190759,P28,F2   wherein K represents a blocked keto group in the form of a ketal, thioketal, oxime or methyloxime, A, B and R2 have the meanings mentioned above, R'1 has the same meaning as R1 but contains a   see diagramm : EP0190759,P28,F3   instead of a   see diagramm : EP0190759,P28,F4   grouping, R'3 has the same meaning as R3 , any hydroxy groups being protected, and R'4 has the same meaning as R4 , any hydroxy or acyl groups being protected, and K1 , in addition to having the meanings mentioned above for K, also represents a hydrogen atom and a protected hydroxy group, is subjected to the influence of a dehydrating agent that is also capable of freeing the protected function(s), in order to split off water while simultaneously forming the 4(5) double bond, a hydroxy group contained in K1 is oxidised, if desired the compounds of general formula I so obtained, with R9 , R10 , R11 and R12 representing one hydrogen atom each, are reacted by microbiological hydroxylation with microorganisms of the species Streptomyces toyocaensis (DSM 40030) and/or Streptomyces platensis (NRRL 2364) and/or Nigrospora sphaerica (CBS 98469) and/or Neurospora crassa (ATCC 9278), and, if desired, the hydroxylated compounds of general formula I so obtained, wherein at least one of the substituents R9 , R10 , R11 and R12 represents a hydroxy group and the remaining substituents represent hydrogen, are epimerised at the positions carrying the hydroxy groups, if desired the hydroxy groups are etherified, esterified or replaced by a halogen or alkyl radical, if desired the hydroxy groups present in R3 and R4 are esterified or etherified, to from the product of general formula I with X representing an oxygen atom and, if desired, reaction is subsequently carried out with hydroxylamine hydrochloride in the presence of tertiary amines at temperatures of between - 20 degrees C and + 40 degrees C.