76 m-フェニレン型PGI_2誘導体の11位水酸基の選択的保護と15位水酸基の反転(ポスター発表の部)

概要

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PGI_2 has potent biological activities but its clinical application had been limited owing to the chemical instability due to a labile enol ether linkage. We reported syntheses of m-phenylene PGI_2 derivatives which had improved chemical stability.^<1)2)3)> However their syntheses need reduction of 15-carbonyl group in final stage to yield a almost 1:1 mixture of α β- and a α-isomer by use of a usual reductant. The trial of the conversion of 15-β-hydroxy group to 15-α-one (Mitsunobu Reaction) prompted us to find a regioselective-protective method of 11-hydroxy group in the presence of 15-hydroxy one. The best protective group was 3,5-dinitrobenzoyl group. The highly selective protection of 11-hydroxy group mainly results from π-π interaction between the phenyl ring (electron donor) in the β-isomer of m-phenylene PGI_2 methyl ester and that (electron acceptor) in the acid chloride. The π-π interaction is characteristic of m-phenylene PGI_2 derivatives and it was supported by the fact that the high selectivity was not seen in a Illoprost derivative which has no phenyl ring.
1990-09-25