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Review
. 2012 Sep 5:4:113-23.
doi: 10.2147/JEP.S27084. eCollection 2012.

The pharmacology and therapeutic potential of (-)-huperzine A

Maung Kyaw Moe Tun  1 , Seth B Herzon  1
Affiliations
Review

The pharmacology and therapeutic potential of (-)-huperzine A

Maung Kyaw Moe Tun et al. J Exp Pharmacol. .

Abstract

(-)-Huperzine A (1) is an alkaloid isolated from a Chinese club moss. Due to its potent neuroprotective activities, it has been investigated as a candidate for the treatment of neurodegenerative diseases, including Alzheimer's disease. In this review, we will discuss the pharmacology and therapeutic potential of (-)-huperzine A (1). Synthetic studies of (-)-huperzine A (1) aimed at enabling its development as a pharmaceutical will be described.

Keywords: Alzheimer’s; NMDA; natural products; neurodegeneration; synthesis.

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Figures

Figure 1
Figure 1
Structures of (−)-huperzine A (1) and (+)-huperzine A (ent-1).
Figure 2
Figure 2
Structures of donepezil (2) and tacrine (3).
Figure 3
Figure 3
Structures of pyridostigmine (4) and physostigmine (5).
Figure 4
Figure 4
Structure of imidazenil (6).
Figure 5
Figure 5
Total syntheses of (−)-huperzine A by Xia and Kozikowski and Qian and Ji.
Figure 6
Figure 6
Improved syntheses of the key β-ketoester intermediate 8. Kozikowski et al’s improved synthesis of the key β-ketoester intermediate 8 (A); Chassaing et al’s and Haudrechy et al’s route to 8 (B).
Figure 7
Figure 7
Yamada et al’s route to (−)-huperzine A (A) and enantioselective Michael addition/aldol condensation by Kaneko et al (B).,
Figure 8
Figure 8
Campiani et al’s palladium-catalyzed annulation strategy (A); Kaneko et al’s and He et al’s asymmetric palladium-catalyzed annulation strategies (B).,
Figure 9
Figure 9
Lee et al’s manganese-mediated oxidative cyclization (A); approach to (±)-huperzine A by Ward and Caprio, and Ward et al (B).
Figure 10
Figure 10
Formal synthesis of huperzine A by Lucey et al (A); total synthesis of (−)-huperzine A (1) by Koshiba et al (B).
Figure 11
Figure 11
Synthesis of (−)-huperzine A (1) by Tun et al.
See this image and copyright information in PMC

References

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