Mass spectrometry studies of Lycopodium alkaloid sauroine

M. G. VALLEJO; D. A. CIFUENTE; F. M. CECATI; M. G. ORTEGA; J. L. CABRERA; V. S. MARTÍN; C. E. TONN; A. M. AGNESE; C. E. ARDANAZ

RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM.

JOHN WILEY & SONS LTD

Año: 2012 vol. 26 p. 2827 - 2831

0951-4198

The Lycopodium alkaloids are quinolizidine or pyridine and a-pyridone type alkaloids from the Lycopodium L., Huperzia Bernh., Lycopodiella Holub, and Phylloglosum Kunze genera, which have unique heterocyclic skeletons of C11N, C15N2, C16N, C16N2, C22N2, and C27N3.[1] During recent years, this group of alkaloids has gained great interest due to their important pharmacological properties as well as for their complex molecular architectures.[2] Recently, an important series of Lycopodium alkaloids have been reported possessing important medicinal effects which can act either as potent inhibitors of acetylcholinesterase (AChE),[3] and/or on memory-related phenomena.[4] It is known that Alzheimer?s disease (AD), a neurodegenerative disease of great socioeconomic impact, is associated with deficits in brain neurotransmitters, especially acetylcholine.[5] This disease is characterized by loss of memory, functional decline and behavioral disturbance. Nowadays, the symptomatic treatment of AD involves restoration of cholinergic function, and drugs inhibiting AChE are the main therapeutic agents used.[6] Currently used AChE inhibitors present side-effects, especially gastrointestinal symptoms, and they are effective in a mild to moderate stage.[7] For this reason, AD therapy is now focused on the discovery of a new receptor targets and other drugs have been developed, which can modulate the glutamatergic neurotransmission. In this respect, the discovery of new Lycopodium alkaloids possessing an activity on learning and on memory seems to be promising in the treatment of AD. The Lycopodium alkaloid sauroine (1), isolated from Huperzia saururus, is a natural product that contains four rings, one as oxadiazolidinone and six stereogenic centers, all in close proximity.[8] Compound 1 (Fig. 1) has shown a marked enhancement of the efficiency for learning and memory processes in animals, and it is not an AChE inhibitor.