LONG-RANGE H-1-N-15 COUPLINGS AND N-15 CHEMICAL-SHIFT ASSIGNMENTS OF THE BIS-INDOLE ANTICANCER DRUG NAVELBINE(R)

The recently reported application of gradient-enhanced HMQC for the ob servation of long-range H-1-N-15 heteronuclear couplings at natural ab undance has been extended to the bis-indole anticancer drug Navelbine( R). Responses correlating protons to N16' (delta N-15 138.2 ppm)in the velbanamine subunit and N1 and N9 (delta N-15 66.0 and 55.3 ppm, resp ectively) in the vindoline subunit were observable within about 4 hour s of data acquisition. The single response to N6' (delta N-15 43.0 ppm ), in contrast, was very weak requiring a weekend data acquisition to even be observed. The difficulty in observing correlations to N6' is p resumably a function of molecular mobility in the eight-membered azoci ne ring.