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-dimensional NMR experiments. They possess a new bisindole skeleton involving an indole alkaloid part B with loss of 5',6'-ethylene, a C7'-C16' linkage, a 14'-O-19'-tetrahydrofuran, and a N-4'-isobutyramide group. The 12-methyl vincorine part A and part B are connected via an 11,10'-biphenyl linkage. The relative configuration was determined by NMR analysis. Biogenetic considerations suggested a rearrangement and a double fragmentation at C6'/C7' and N4'/C5' for the formation of 1 from strictamine, further allowing deduction of the absolute configuration of 10 stereocenters: 2S, 7R, 15R, 16R, 3'R, 14'S, 15'S, 16'R, 19'S, and 20'R. The alkaloids 1 and 2 display, in vitro, cytotoxic activity against nasopharynx carcinoma KB cells, IC(50) 5 and 6 &mgr;M (4 and 5 &mgr;g/mL).