A New Structural Class of Bisindole Alkaloids from the Seeds of Catharanthus roseus: Vingramine and Methylvingramine

Abstract

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).

Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer, Part 2: A Review on Cytotoxic, Antiproliferative, and Antitumor Phytochemicals, and Future Perspective

“…This is one of the most precious anticancer plants indigenous to Madagascar. Previously, approximately 30 bis-indole alkaloids and over 60 monomeric indole alkaloids have been isolated from the aerial parts and roots of C. roseus [ 85 , 86 ]. Wang et al [ 87 ] isolated three new cytotoxic dimeric indole alkaloids ( 32 – 34 ) along with other five known compounds from the whole plant of C. roseus collected from China ( Table 4 ).…”

The Lactone Concept: An Efficient Pathway to Axially Chiral Natural Products and Useful Reagents

“…One reason for this is the growing number of isolated biaryl natural products, 1-3 leading to a broad structural, biosynthetical, and pharmacological variety, e.g. dimeric sesquiterpenes like gossypol () 4 or biscarbazoles like bismurrayaquinone A (), 5,6 but also mixed, constitutionally unsymmetric biaryls such as knipholone (), 7,8 naphthylisoquinoline alkaloids 2,9 like dioncophylline A (3-) 10,11 , and bisindole alkaloids like vingramine () 12 -some of them being additionally equipped with stereogenic centers ( Figure 1). Besides their largely divergent structures, these natural products are fascinating and rewarding research objects also for their numerous bioactivities like antispermatogenic, 13 antimalarial, [14][15][16] nerve growth stimulating, 17 and molluscicidal properties.…”

Collected mass spectrometry data on monoterpene indole alkaloids from natural product chemistry research

“…Although none of these were previously described in C. roseus , both these structural assignments can be deemed reasonable based on biosynthetic considerations. Being an akuammiline-derived MIA, such as akuammine 21 and the monomer precursors of the bisindoles vingramine and methylvingramine 22 that have been reported to occur in C. roseus , the detection of burnamine is not unexpected. Likewise, the co-dereplication in the depicted molecular network of the formerly described vobasane-type perivine supports the identification of vobasine within this plant.…”