Korupensamines A-D, novel antimalarial alkaloids from Ancistrocladus korupensis

Four novel C5/C8'-linked naphthyltetrahydroisoquinolines 1-4, named korupensamines A-D, along with the tetrahydroisoquinoline 5, were isolated from extracts of the tropical liana Ancistrocladus korupensis. The structures of these alkaloids were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute configuration of korupensamine A was initially deduced from X-ray crystallographic analysis of the p-bromobenzenesulfonate derivative 6 and later confirmed by chemical degradation of 1 to known amino acids. Chemical degradation also established the absolute configuration of the whole series 1-5. The related dimeric compounds, michellamines A, B, and C, previously reported from the same plant, are active against HIV-1 and HIV-2; however, the ''monomeric'' compounds reported herein are essentially inactive against HIV. In contrast, the ''monomers'' 1 and 2 are active in vitro against malaria parasites Plasmodium falciparum and P. berghei, whereas the michellamines exhibit only very weak antimalarial activity.