Chemical and biological aspects of Narcissus alkaloids

Abstract

This chapter discusses the chemical and biological aspects of Narcissus alkaloids. Numerous alkaloids have been isolated from Narcissus speciesasaresult of the continuing search for novel alkaloids with pharmacological activity in the Amaryllidaceae family. The alkaloids isolated from this genus, classified in relation to the different skeleton types. The different Narcissus wild species and intersectional hybrids, grouped into subgenera and sections, with their corresponding alkaloids, arranged according to their ring system are listed. The biosynthetic pathways of Narcissus alkaloids includes: (1) enzymatic preparation of the precursors, (2) primary cyclization mechanisms, (3) enzymatic preparation of intermediates, (4) secondary cyclization, diversification, and restructuring. The chapter discusses proton nuclear magnetic resonance (¹H NMR), carbon nuclear magnetic resonance (¹³C NMR), and mass spectrometry (MS) for Narcissus alkaloids. A list of the different Narcissus alkaloids, their spectroscopic properties, and literature with the most recent spectroscopic data is given. Several Narcissus extracts shows the following activities: antiviral, prophage induction, antibacterial, antifungal, antimalarial, insecticidal, cytotoxic, antitumor, antimitotic, antiplatelet, hypotensive, emetic, acetylcholine esterase inhibitory, antifertility, antinociceptive, chronotropic, pheromone, plant growth inhibitor, and allelopathic.

Figure 1

Amaryllidaceae alkaloid types.

Figure 2

Biosynthetic pathway to norbelladine (93).

Figure 3

Phenol oxidative coupling in Amaryllidaceae alkaloids.

Figure 4

Alkaloids proceeding from an ortho–para′ coupling.

Figure 5

Biosynthesis of lycorine (1) with inversion of the configuration.

Figure 6

Conversion of galanthine (7) to narcissidine (16) via epoxide (94).

Figure 7

Conversion of norpluviine (12) to homolycorine-type alkaloids.

Figure 8

Alkaloids proceeding from a para–para′ coupling.

Figure 9

Biosynthesis of pretazettine (64).

Figure 10

Proposed biosynthetic pathways to hemanthamine (53) and montanine (98).

Figure 11

Biosynthesis of galanthamine (75) and derivatives.

Scheme 1

Synthesis of racemic narwedine (83) and galanthamine (75).

Scheme 2

Diversity-oriented synthesis of galanthamine-like compounds.

Scheme 3

Synthesis of plicamine and obliquine using solid-supported reagents.

Scheme 4

Palladium-mediated synthesis of galanthamine (75).

Scheme 5

Enantioselective synthesis of (−)-galanthamine (75).

Scheme 6

Synthesis of narciclasine (68).

Scheme 7

Synthesis of epi-7-deoxypancratistatin.

Scheme 8

Radical synthesis of lycoricidine.

Scheme 9

Radical synthesis of vasconine (22), assoanine (20), oxoassoanine (21), and pratosine.

Scheme 10

Synthesis of racemic pancratistatin.

Scheme 11

Synthesis of narciclasine (68) and pancratistain.

Scheme 12

Synthesis of γ-lycorane, 1-deoxylycorine, and epi-zephyranthine.

Scheme 13

Synthesis of 7-deoxypancratistatin.

Scheme 14

Total synthesis of lycoricidine.

Scheme 15

Synthesis of 2,7-dideoxypancratistatin from d-(−)-quinic acid.

Figure 12

Mass fragmentation pattern of lycorine (1).

Figure 13

Mass fragmentation pattern of homolycorine (26).

Figure 14

Mass fragmentation pattern of hemanthamine (53).

Figure 15

Mass fragmentation pattern of tazettine (62) and criwelline (63).

Figure 16

Mass fragmentation pattern of montanine (98).

Figure 17

Mass fragmentation pattern of galanthamine (75).