Long‐range ¹H‐¹⁵N couplings and ¹⁵N chemical shift assignments of the bis‐indole anticancer drug navelbine®

The recently reported application of gradient‐enhanced HMQC for the observation of long‐range 1 H‐ 15 N heteronuclear couplings at natural abundance has been extended to the bis‐indole anticancer drug Navelbine®. Responses correlating protons to N16′ (δ 15 N 138.2 ppm)in the velbanamine subunit and N1 and N9 (δ 15 N 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′ (δ I5 N 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.