Impacts of Steric Compression, Protonation, and Intramolecular Hydrogen Bonding on the (15)N NMR Spectroscopy of Norditerpenoid Alkaloids and Their Piperidine-Ring Analogues

[Image: see text] (1)H–(15)N HMBC spectra of norditerpenoid alkaloids and their synthetic azabicyclic analogues were obtained to investigate the impacts of the through-space effect of steric compression, protonation, and formation of intramolecular hydrogen bonding on the (15)N NMR spectroscopy of these natural products and their piperidine-containing analogues. A rare (15)N NMR effect of steric compression is demonstrated in half-cage A/E-rings of norditerpenoid alkaloid free bases and their synthetic azabicyclic analogues, in which the distribution of the lone pair of electrons of the tertiary amine N-atom is sterically restricted by bridged cycloalkanes, e.g., cyclopentane, cyclohexane, and cycloheptane rings. This results in significant changes in the (15)N chemical shift, typically by at least ∼10 ppm. The lone pair of electrons of the N-atom in the piperidine ring are sterically compressed whether the bridged cyclohexane ring adopts a chair or boat conformation. The (15)N chemical shifts of 1α-OMe norditerpenoid alkaloid free bases significantly increase (Δδ(N) ≥ 15.6 ppm) on alkaloid protonation and thence the formation of an intramolecular hydrogen bond between N(+)-H and 1α-OMe. The intramolecular hydrogen bonds between the N-atom and 1α-OH of 1α-OH norditerpenoid alkaloid free bases, karacoline, condelphine, and neoline stabilize their A-rings, adopting an unusual twisted-boat conformation, and they also significantly increase δ(N) of the tertiary amine N-atom.