Complete 1H NMR spectral fingerprint of huperzine A

Complete analysis of the H-1 NMR spectrum of huperzine A, 1-amino-13-ethylidene-11-methyl-6-aza-tricyclo[7.3.1.0(2,7)]trideca-2(7),3,10-trien-5-one, a Lycopodium alkaloid and anti-Alzheimer drug lead containing an ABCD(E)(MN)(OP)X(3)y(3)-type system of 15 nonexchangeable proton spins, is reported for the first time, and earlier assignments are corrected. The complete H-1 parameter set of 11 chemical shifts clarifies the diastereotopism of both methylene groups, and provides a total of 38 observed H,H-couplings including 31 long-range ((4-6)J) connectivities. The NMR data is consistent with the comparatively rigid alicyclic backbone predicted by molecular mechanics calculations, and forms the basis for H-1 NMR fingerprint analysis for the purpose of dereplication, purity analysis, and elucidation of structural analogs. Copyright 2007 John Wiley & Sons, Ltd.