Circular dichroism studies of bisindole Vinca alkaloids

The analysis of a series of seventeen vinblastine analogs by circular dichr oism is described. Exciton coupling of the indole and indoline chromophores of these compounds provides a general, nonempirical method for the assignm ent of the C16' configuration with the bioactive C16'-S and the inactive C1 6'-R analogs giving rise, respectively, to positive and negative couplets. An analysis of the noncoupled transitions of the CDs indicates that a posit ive Cotton effect at 305 nm, although empirical, is associated with bioacti vity. Theoretical calculations of the UV and CD spectra of vinblastine dias tereomers are also described. (C) 1998 Elsevier Science Ltd. All rights res erved.