Ancistrocladinium A and B, the First N,C-Coupled Naphthyldihydroisoquinoline Alkaloids, from a Congolese Ancistrocladus Species

Abstract

The isolation and structural elucidation of three novel-type naphthylisoquinoline alkaloids, ancistrocladinium A and B (the latter along with its atropisomer), from a Congolese Ancistrocladus species collected in the habitat Yeteto is reported. Their structures, including all stereochemical features, were elucidated by spectroscopic, chemical, and chiroptical methods. Ancistrocladinium A and B are the first N,C-coupled naphthyldihydroisoquinoline alkaloids found in nature, i.e., with an iminium-aryl axis. Although ancistrocladinium A, which is N,8¢-coupled, is configurationally stable at this axis, ancistrocladinum B and its rotational isomer are based on a hitherto unprecedented N,6¢-coupling type, with a slow rotation about the hetero biaryl axis at room temperature; they thus occur as a 46:54 mixture of two configurationally semistable atropo-diastereomers. For the isomerization of (P)-ancistrocladinium B to its (M)-diastereomer and for the opposite direction, the Gibbs free energies of activation were determined to be ¢Gq 1 ) 105.8 kJ mol-1 and ¢Gq 2 ) 105.7 kJ mol-1, respectively. In addition, the compounds were shown to have promising antileishmanial activities.