GB1031078A - New yohimbane compounds and a new process for their manufacture - Google Patents

Abstract

17a - Hydroxy - 18b - acyloxy - 20a - yohimbane - 16b 8 carboxylic acid esters, including novel compounds of general formula <FORM:1031078/C2/1> wherein R is acyl, R1 is a lower alkyl group optionally substituted by a lower alkoxy group a di-(lower-alkyl) amino group, a lower alkyleneimino group, or a morpholino, thiamopholino or piperazino group, R4 + R5 are hydrogen, lower alkoxy, lower alkyl, lower alkylmercapto, phenyl-lower alkoxy, di-(lower alkyl) amino or halogen, or R4 + R5 in vicinal positions together represent a methylenedioxy group and R6 is hydrogen or lower alkyl and where lower is used above it means groups containing up to 7 carbon atoms (pseudoresepine, raunescine and neocindine and disclaimed as not being novel); and their N-oxides and acid addition salts, are prepared by hydrogenolysis or acid hydrolysis of the corresponding 17-ethers or 17-esters or N-oxides or acid addition salts thereof, including novel 17a - tetrahydropyranyl - (2) - oxy - 18b - acyloxy-3b ,20a - yohimbane - 16b - carboxylic acid esters, in which the ester or ether is difficult to eliminate by alkaline hydrolysis, e.g. oxacycloalkyl-(2) ethers with at least 5 atoms as ring members and carbobenzoyl esters. The above 17-ethers and -esters are prepared by a process wherein in a 16,18-lactone of a 17a ,18b - dihydroxy - 20a - yohimbane - 16b -carboxylic acid or an N-oxide or acid addition salt thereof, the 17-hydroxyl group is etherified or esterified with a group which is difficult to eliminate by alkaline hydrolysis but easy to eliminate by hydrogenolysis or acid hydrolysis, the resulting lactone, which may be novel 17 - O - tetrahydropyranyl - pseudoreserpic acid lactone, is split with an alkaline reagent or by alcoholysis any resulting compound containing a free carbocyclic group in the 16-position is esterified and the hydroxy group in the 18-position is acylated. A product obtained above at any stage may be isomerized in the 3-position and/or any resulting compound may be oxidized to the N-oxide and/or an N-oxide may be reduced and/or a base may be converted into an acid addition salt or an acid addition salt may be converted into a free base. 16,18 - Lactones of 17a ,18b - dihydroxy-20a -yohembane 16b -carboxylic acids are prepared by formation of the lactone ring from the free acid by heating in the presence of N,N1-dicyclohexyl-carbodiimide. Pharmaceutical or veterinary compositions in conventional forms for enteral or parenteral administration and animal feedstuffs contain a hereinbefore mentioned novel compound and a carrier therefor.