Complete ¹H NMR spectral fingerprint of huperzine A

Abstract

Complete analysis of the (1)H 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 (1)H 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 (1)H NMR fingerprint analysis for the purpose of dereplication, purity analysis, and elucidation of structural analogs.

Stereochemical Analysis of Leubethanol, an Anti-TB-Active Serrulatane, fromLeucophyllum frutescens

“…The methodology of full 1 H NMR spin analysis has been pioneered by Laatikainen, Niemitz, and co-workers, and previously been documented for a few natural products including alkaloids and mono-, sesqui-, and diterpenes. 13–17 The method involves iterated quantum-mechanical simulation of the entire spin system of the molecule until full congruence is achieved between the experimental and simulated spectrum.…”

Essential Parameters for Structural Analysis and Dereplication by 1H NMR Spectroscopy

“…Further perspectives for the importance of adequate precision in HNMR data reporting are provided by reported case studies of molecules that have been subjected previously to full spin analysis, recently referred to as HiFSA ( 1 H iterative full spin analysis): 9 the monoterpene β-pinene, 10 the sesquiterpenoid perezone and its analogues, 11 the diterpenoid ent-3β-hydroxytrachylobane, 12 a series of diterpenoid lactones (ginkgolides) and flavonoids from Ginkgo biloba L., 13,14 several alkaloids such as huperzine A, 15 indole derivatives, 16 anatabine 17 analogues from Nicotiana species, tropane derivatives, 18 flavonoids 19 and flavonolignans, and dimeric phenylpropanoids ([iso]silybins) from Silybum marianum (L.) Gaertn., 20 as well as mono- and oligosaccharides. 21 …”

Photohuperzine A—A new photoisomer of huperzine A: Structure elucidation, formation kinetics and activity assessment

“…The structure of 2 was further elucidated by 1 H, 13 C, APT, HSQC, COSY, HMBC and NOESY NMR measurements. In Table 1, the spectroscopic data are summarized.…”

“…The commonly accepted biosynthetic numbering of 1 [13] was also applied to 2 (see Fig. 1) and is used in discussing the interpretation of the NMR data below.…”