An Efficient Total Synthesis of (±)-Galanthamine

Guillou, Catherine; Beunard, Jean‐Luc; Gras, Emmanuel; Thal, C.

doi:10.1002/1521-3757(20011217)113:24<4881::aid-ange4881>3.0.co;2-r

Cited by 20 publications

(6 citation statements)

References 26 publications

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“…Galanthamine is produced on a large scale from Bulgarian Leucojum aestivum [4] and also by chemical synthesis [5][6][7]. However, the synthesis is complicated and time consuming because galanthamine has three asymmetric carbons requiring stereochemically controlled synthesis.…”

Section: Introductionmentioning

confidence: 99%

Influence of auxins on somatic embryogenesis and alkaloid accumulation in Leucojum aestivum callus

et al. 2013

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In vitro cultures of Leucojum aestivum are considered as an alternative for the production of galanthamine, which is used for the symptomatic treatment of Alzheimer’s disease. We studied the effects of auxins 2,4-dichlorophenoxyacetic acid (2,4-D), 4-amino-3,5,6-trichloropicolinic acid (picloram), 3,6-dichloro-o-anisic acid (dicamba) at concentrations of 25 and 50 µM on the induction of embryogenic callus and its capacity to induce somatic embryogenesis and alkaloid accumulation. The embryogenic response of the explants was from 30% for 25 µM of dicamba to 100% for picloram (for both 25 and 50 µM). 2,4-D (50 µM) stimulated greater callus proliferation and somatic embryo induction as compared to the other auxins. Polyethylene glycol (PEG) stimulated somatic embryo maturation. Callus grown on media containing 50 µM of auxins produced fewer phenolic compounds as compared with callus grown on media containing 25 µM of auxins. GC-MS analyses showed seven alkaloids in the in vivo bulbs and two to four in callus culture. Galanthamine was detected in callus cultivated with 2,4-D (25, 50 µM), picloram (25 µM), and dicamba (50 µM). Other alkaloids, trisphaeridine, tazettine, and 11-hydroxyvittatine were accumulated only in callus growing on medium with picloram (50 µM).

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Section: Introductionmentioning

confidence: 99%

Influence of auxins on somatic embryogenesis and alkaloid accumulation in Leucojum aestivum callus

et al. 2013

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“…For medical applications, it is obtained via a low-yielding and complex total synthesis (Guillou et al 2001;Marco-Contelles et al 2006), but it has also been isolated from Leucojum aestivum bulbs in particular (Berkov et al 2005). A number of studies have reported that Gal is accumulated in Amaryllidaceae tissue cultures and that some factors can enhance its accumulation (Selles et al 1997;Colque et al 2004;Diop et al 2007;Diop et al 2006;Ptak et al 2009;Georgiev et al 2009;Berkov et al 2009a, b;Ptak et al 2010), suggesting that biotechnological methods can be considered as an alternative approach for the production of this alkaloid.…”

Section: Introductionmentioning

confidence: 99%

Effects of sucrose and plant growth regulators on acetylcholinesterase inhibitory activity of alkaloids accumulated in shoot cultures of Amaryllidaceae

Tahchy

Bordage

Ptak

et al. 2011

Plant Cell Tiss Organ Cult

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The influence of sucrose (30, 60, 90 and 120 g/L), activated charcoal (5 and 10 g/L), and various levels of several plant growth regulators (6-benzyladenine, naphthalene-1-acetic acid, 2,4-dichlorophenoxyacetic acid, and picloram) on organogenesis (bulb and root development) and the accumulation of alkaloid and galanthamine in shoot cultures of three Amaryllidaceae species (Narcissus pseudonarcissus, Galanthus elwesii, and Leucojum aestivum) was investigated in a full-factorial experiment. Alkaloid extracts were analyzed by gas chromatographymass spectrometry, leading to the quantification of galanthamine and to the identification of other alkaloids. The different extracts were then subjected to an Ellman test to evaluate the inhibitory activity of acetylcholinesterase. The highest contents of galanthamine [0.02-0.1% dry weight (DW) depending on the plant species] were always accompanied with a high level of acetylcholinesterase inhibition ([30%). However, some samples containing low amounts of galanthamine (0.005% DW) showed high inhibitory activities (40-80%). These findings demonstrate the presence of Amaryllidaceae alkaloids that have not yet been identified as having anti-acetylcholinesterase activity.

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“…The two main commercial sources of galanthamine are organic synthesis and plant extraction; the first one is low yielding and complex [12,13], the second is limited by several factors: the low concentration of galanthamine in plants (variation from trace to 0.5% [14]), seasonal variation [15]. Besides, overharvesting is causing depletions of wild Amaryllidaceae populations [16].…”

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Stimulating effect of both 4’‐O‐methylnorbelladine feeding and temporary immersion conditions on galanthamine and lycorine production by Leucojum aestivum L. bulblets

Saliba

Ptak

Boisbrun

et al. 2016

Engineering in Life Sciences

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Bulb cultures of Leucojum aestivum and L. aestivum 'Gravety Giant' were subcultured in medium containing the precursor 4'-O-methylnorbelladine (MN) at various concentrations [0 (control), 0.15 and 0.3 g/L]. The cultures were conducted in bioreactor RITA R and lasted for 15, 30, 40 and 50 days. The growth rate and the alkaloid accumulation in bulblets were studied. For this latter purpose, a purification method was developed. It comprised a highly selective solid phase extraction using on the one hand, UPTI-CLEAN SI and SCX cartridges for plant extracts and on the other hand, 2H cartridges for culture media. Pure alkaloidal fractions were, thus, analyzed by LC-ESI-MS allowing the quantitative evaluation of galanthamine and lycorine from culture extracts. Precursor feeding along with temporary immersion conditions was found to significantly improve the accumulation of both galanthamine and lycorine. The maximal concentrations of galanthamine (0.81 mg/g DW) and lycorine (0.54 mg/g DW) in L. aestivum bulblets were reached, respectively, after 40 days of culture with 0.15 g/L of precursor and after 30 days of culture with 0.3 g/L of precursor. In L. aestivum 'Gravety Giant' bulb cultures, 0.3 g/L of precursor was the best condition for both galanthamine (0.6 mg/g DW after 50 days) and lycorine (1.13 mg/g DW after 30 days).

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An Efficient Total Synthesis of (±)-Galanthamine

Cited by 20 publications

References 26 publications

Influence of auxins on somatic embryogenesis and alkaloid accumulation in Leucojum aestivum callus

Influence of auxins on somatic embryogenesis and alkaloid accumulation in Leucojum aestivum callus

Effects of sucrose and plant growth regulators on acetylcholinesterase inhibitory activity of alkaloids accumulated in shoot cultures of Amaryllidaceae

Stimulating effect of both 4’‐O‐methylnorbelladine feeding and temporary immersion conditions on galanthamine and lycorine production by Leucojum aestivum L. bulblets

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