Isoquinoline Alkaloids Alkaloids Derived from Phenylalanine and Tyrosine 1.
Alkaloids)–Introduc1on)and)Importance)to)Humans)web.uvic.ca/~cpc/18.AlkaloidSlides2017.pdf ·...
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Alkaloids – Introduc1on and Importance to Humans
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Alkaloids – Introduction and Importance to Humans (alkaloids are pharmaceutically and ecologically significant)
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Introduc)on to alkaloids, and importance to humans
Define: = small organic molecules (secondary metabolites) of plants which contain nitrogen (typically in a ring)
-‐ alkaloids are pharmaceu)cally significant
-‐ tradi1onal and modern uses (25%/75% of drugs are plant derived, mostly alkaloids)
-‐ many have neurological effects -‐ presumed due to the presence of nitrogen (mimic neutrotransmiEers)
-‐ potent toxins and defenses -‐ many highly toxic compounds, and with strong biological effects
-‐ interes1ng chemical ecology and co-‐evolu1on with insects
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Alkaloid physiological effects are diverse:
Quinine (Cinchona officinalis) -‐an)bio)cs (an1-‐malarial)
Morphine (Papaver somniferum -‐ painkiller (analgesic)
Taxol -‐ (Taxus brevifolia)
Vinblas)ne (Catharanthus roseus) -‐ an)cancer drug
Coniine (Conium maculatum) -‐ toxin
Nico)ne (Nico@ana tabacum) insec1cide, s1mulant
Atropine(Atropa belladonna) dilate pupils
Cocaine (Erythroxylon coca) –
Tubocurarine (Chondodenron tomentosum) -‐ muscle relaxant
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General Features and Characteris)cs
-‐ N makes them basic in solu1on -‐> called alkaloids for this reason
-‐ structurally diverse: 12,000+ structures
-‐ 20% of all plant species have alkaloids
-‐ concentrated in specific plant taxa (families, genera, species), but are 'scaEered around' the plant kingdom (independent evolu1on)
-‐ biosynthe1cally diverse (arise from different amino acids)
-‐ strong biological effects (see ecological examples)
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Examples of diverse mechanisms of ac)on:
-‐ bind/block neuroreceptors (morphine, codeine)
-‐ block reuptake of neuroreceptor (cocaine-‐dopamine)
-‐ disrupt cytoskeleton -‐ tubulin (taxol)
-‐ mimic neurotransmiKer ac)on (nico1ne -‐ acetylcholine)
-‐ block cellular signaling (cAMP phosphodiesterase -‐ caffeine)
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Alkaloid Families and Biosynthesis (mostly derived from amino acids)
Heldt, Fig 16.1
Non-protein amino acids: – not considered alkaloids but also toxins
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α-solanidine (tripterpene alkaloid of potato)
Pseudoalkaloids: N added late in biosynthesis
Protoalkaloids: N not in ring
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Biosynthesis of Alkaloids
General features of alkaloid biosynthesis:
-‐ many biosynthe1c steps are required -‐> complex structures
-‐ any one plant typically accumulates a mix of related alkaloids
-‐ usually begins with decarboxyla)on of amino acid (eg) tyr -‐> tyramine, trp -‐> tryptamine
-‐ central intermediate can give rise to different final products: (strictosidine for diverse quinoline alkaloids, re)culine for isoquinoline and poppy alkaloids)
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C. Bowsher, Plant Biochemistry p. 342
Biosynthesis of Quinoline Alkaloids & Central Position of Strictosidine
Strictosidine
Vincristine/ Vinblastine (monoterpene indole alkaloids
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C. Bowsher, Plant Biochemistry p. 344-46
Central Position of Reticuline in Isoquinoline Alkaloid Synthesis
Isoquinoline Alkaloids Reticuline
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Alkaloids can have organ-‐specific synthesis and storage:
i.e., bark, roots, flowers
There is also cell-‐specific synthesis / storage:
-‐ latex ducts and la1cifers for poppy alkaloids
-‐ epidermis, idioblasts for Vinca alkaloids
Biosynthesis of Alkaloids
Opium poppy (Papaver somniferum)
Madagascar periwinkle (Catharanthus roseus)
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Localiza1on of alkaloid synthesis opium poppy
Biosynthesis of components in different cell types:
-‐ root and phloem parenchyma cell -‐ la1cifers and idioblasts (DAT)
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Localiza1on of Vinca alkaloid synthesis in Madagascar periwinkle (Catharantus roseus)
Biosynthesis of components in different cell types:
-‐ phloem parenchyma cells (DXS, DXR) -‐ epidermis (TDC, STR) -‐ la1cifers and idioblasts (DAT)
phloem parenchyma cells
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Catharanthine accumulates almost en1rely in leaf wax exudates outside of the leaf epidermis, whereas vindoline is found within leaf cells.
Roepke J et al. PNAS 2010;107:15287-15292
©2010 by National Academy of Sciences
leaf surface (chloroform wash)
chloroform wash
whole leaf extract aaer chloroform wash
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Model for biosynthesis and secre1on of secondary metabolites produced in the epidermis of C. roseus leaves.
Roepke J et al. PNAS 2010;107:15287-15292
©2010 by National Academy of Sciences
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Catharanthine is toxic to insect larvae (silk worm)
Catharanthine is also toxic to pathogenic fungi (not shown)