FOERFARANDE FOER FRAMSTAELLNING AV NYA 2,3,4-TRINOR-M-INTER-FENYLEN-PROSTA-CYKLINDERIVAT MED BLODPLATTEAGGREGATIONSHAEMMANDE EFFEKT.

摘要

2,3,4-trinor-1,5-inter-m-phenylene-prostacycline derivatives of the formula (I), (I) wherein R1 is hydrogen, a C1-4 alkyl group, an alkali metal cation or a primary, secondary, tertiary or quaternary ammonium cation, R2 and R3 each represent hydrogen or a C1-4 alkanoyl, benzoyl, substituted benzoyl, tetrahydropyranyl, ethoxyethyl or tri-(C1-4 alkyl)-silyl group, R4 is hydrogen or a C1-4 alkyl group, and R5 is a hexyl, heptyl, phenoxymethyl or m-trifluoromethylphenoxymethyl group, or R5 represents a group of the general formula and in this latter formula Z is an amino group or an optionally halo-substituted C1-4 alkanoylamino, benzoylamino or tosylamino group, and R6 is a C4-6 alkyl, phenyl or benzyl group, are prepared by reacting a bicyclic lactol of the formula (II), (II) with a reactive phosphorane prepared from a triphenyl-m-carbobenzylphosphonium halide and a strong base, optionally esterifying the resulting prostaglandin derivative and, whenever it contains a free amino group, protecting this amino group by acylation, reacting then the prostaglandin derivative with an electrophilic reagent of the formula E-X, wherein X is halogen atom and E is halogen atom or an acetyl, trifluoroacetyl or N-succinimido group, and subjecting the resulting halogenated PGI1 derivative to hydrogen halide elimination. The compounds of the formula (I) possess valuable biological effects and can be applied in therapy primarily as blood platelet aggregation inhibiting agents.