Synthesis and biological evaluation of analogues of cryptolepine, an alkaloid isolated from the Suriname rainforest

Bioassay-guided fractionation of an extract of a mixture of Microphilis guy anensis and Genipa americana collected in the rainforest of Suriname yielde d the known alkaloid cryptolepine (2) as the major active compound in a yea st bioassay for potential DNA-damaging agents; the same compound was later reisolated from M. guyanensis. The structure of cryptolepine was identified unambiguously by spectral data and by its total synthesis. Several cryptol epine derivatives (3-29, 32-41) were synthesized based on modifications of the C-2, N-5, N-10, and C-11 positions. Two cryptolepine dimers (30, 31) we re also prepared. The structure modifications did not result in compounds w ith a higher potency than the parent compound cryptolepine in the yeast ass ay system, although some derivatives did show significant activity. Selecte d compounds (6, 7, 17, 22, 23, 26, and 27) were also tested for cytotoxicit y in mammalian cell culture, and two compounds showed significant cytotoxic activity.