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 observation of long-range H-1-N-15 heteronuclear couplings at natural abundance 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, respectively) in the vindoline subunit were observable within about 4 hours 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 presumably a function of molecular mobility in the eight-membered azocine ring.