The synthesis of emetine and related compounds. Part X. The synthesis of emetine analogues, including C(3)-bisnoremetine and C(3)-noremetine. Correlation of structure with amoebicidal activity

Abstract

The (±)-ketone (Ia)(1,3,4,6,7,11b-hexahydro-9,10-dimethoxybenzo[a]quinolizin-2-one) has been converted into racemic C(3)-bisnoremetine (IXa)via and N-(3,4-dimethoxyphenethyl) amide which was shown to have the same relative configuration as emetine at C-11b and C-2. The (–)-ketone (Ib)[3-methyl derivative of (Ia)], obtained by asymmetric transformation of the racemic compound, was converted into (–)-C(3)-noremetine (IXb). (–)-1′,8a′-Secoemetine (XI) and the (–)-analogues (XIIa–d) have also been prepared. Only compounds (IXa), (IXb), and (XI) showed appreciable amoebicidal activity.