A NEW STRUCTURAL CLASS OF BISINDOLE ALKALOIDS FROM THE SEEDS OF CATHARANTHUS-ROSEUS - VINGRAMINE AND METHYLVINGRAMINE

Two new bisindole alkaloids, vingramine (1) and methylvingramine (2), were isolated from the seeds of Catharanthus roseus, Apocynaceae. The structures were determined by HRFABMS as well as one- and two-dimensio nal NMR experiments. They possess a new bisindole skeleton involving a n indole alkaloid part B with loss of 5',6'-ethylene, a C7'-C16' linka ge, a 14'-O-19'-tetrahydrofuran, and a N-4'-isobutyramide group. The 1 2-methyl vincorine part A and part B are connected via an 11,10'-biphe nyl linkage. The relative configuration was determined by NMR analysis . Biogenetic considerations suggested a rearrangement and a double fra gmentation at C6'/ C7' and N4'/C5' for the formation of 1 from stricta mine, further allowing deduction of the absolute configuration of 10 s tereocenters: 2S, 7R, 15R, 16R, 3'R, 14'S, 15'S, 16'R, 19'S, and 20'R. The alkaloids I and 2 display, in vitro, cytotoxic activity against n asopharynx carcinoma KB cells, IC50 5 and 6 mu M (4 and 5 mu g/mL).