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Review
. 2020 May 16;25(10):2337.
doi: 10.3390/molecules25102337.

Chemical and Biological Aspects of Montanine-Type Alkaloids Isolated from Plants of the Amaryllidaceae Family

Darja Koutová  1 , Negar Maafi  2 , Radim Havelek  1 , Lubomír Opletal  2 , Gerald Blunden  3 , Martina Řezáčová  1 , Lucie Cahlíková  2
Affiliations
Review

Chemical and Biological Aspects of Montanine-Type Alkaloids Isolated from Plants of the Amaryllidaceae Family

Darja Koutová et al. Molecules. .

Abstract

Plants of the Amaryllidaceae family are promising therapeutic tools for human diseases and have been used as alternative medicines. The specific secondary metabolites of this plant family, called Amaryllidaceae alkaloids (AA), have attracted considerable attention due to their interesting pharmacological activities. One of them, galantamine, is already used in the therapy of Alzheimer's disease as a long acting, selective, reversible inhibitor of acetylcholinesterase. One group of AA is the montanine-type, such as montanine, pancracine and others, which share a 5,11-methanomorphanthridine core. So far, only 14 montanine-type alkaloids have been isolated. Compared with other structural-types of AA, montanine-type alkaloids are predominantly present in plants in low concentrations, but some of them display promising biological properties, especially in vitro cytotoxic activity against different cancerous cell lines. The present review aims to summarize comprehensively the research that has been published on the Amaryllidaceae alkaloids of montanine-type.

Keywords: Amaryllidaceae; alkaloids; biological activity; derivatives; montanine; montanine-type; pancracine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biosynthetic pathway of main structural types of Amaryllidaceae alkaloids.
Figure 2
Figure 2
Proposed biosynthesis of montanine and pancracine, according to Feinstein and Wildman [23].
Figure 3
Figure 3
Proposed biosynthetic pathway for montanine-type, according to Jin [25].
Figure 4
Figure 4
Chemical structures of montanine-type Amaryllidaceae alkaloids.
Figure 5
Figure 5
Tentative mechanism for haemanthamine-montanine skeletal rearrangement, according to Govindaraju et al. [.
Scheme 1
Scheme 1
Preparation of C2-derived montanine-type derivatives, in order to study antiproliferative potential. Reagents and conditions for synthesis: (a) MsCl, py, 0 °C, 8 h, then MeOH, NaH (yield 65%); (b) MsCl, Et3N, CH2Cl2, rt, 48 h, (yield 55%) (c) MsCl, py, 0 °C, 8 h, then aq. NaHCO3 (yield 74%); (d) MsCl, py, 0 °C, 8 h, then EtOH, NaH (yield 65%); (e) MsCl, py, 0 °C, 8 h, then CH2=CH-CH2-OH, NaH (yield 68%) (f) MsCl, py, 0 °C, 8 h, then CH≡C-CH2-OH, NaH (yield 50%) (g) MsCl, py, 0 °C, 8 h, then BnNH2, NaH (yield 67%); (h) MsCl, py, 0 °C, 8 h, then indole, NaH (yield 62%); (j) MsCl, py, 0 °C, 8 h, then pyrrole, NaH (yield 55%).
Scheme 2
Scheme 2
Further modifications of montanine derivatives and rearrangement of haemanthidine. Reagents and conditions for synthesis: (a) m-CPBA, CH2Cl2, rt, 30 min, (yield 70%); (b) MeCN, rt, CH≡C-CH2-Br, 24 h, (yield 78%) (c) NIS (2.4 eq), In(OTf)3, MeCN, 45 °C, 12 h, (yield 55%); (d) NIS, In(OTf)3, MeCN, 45 °C, 12 h, (yield 72%); (e) CBr4, Ph3P, CH2Cl2, rt, 4 h, (yield 64%) (f) MsCl (4 eq), py, 0 °C, 8 h, then aq. NaHCO3 (yield 46%).
Scheme 3
Scheme 3
Preparation of further derivatives of montanine-type AA by rearrangement from haemanthamine and haemanthidine. Reagents and conditions for synthesis: (a) DAST, DCM, −78 °C, 24 h, (yield for 15 60%; yield for 16 49%).
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