Chemistry of alkaloids (spring) Flashcards
name common alkaloids and draw their structure
where do alkaloids come from?
They occur naturally and are produced by plants, fungi and animals
Why produce alkaloids?
Nicotine is a secondary metabolite of various plants (high concentrations in tobacco plants, but also found in other members of Solanaceae). Toxic to insects, so thought to be an insect antifeedant (produced by the plant in response to herbivory). One of the first compounds to be used as an insecticide.
Senecionine is one example of an alkaloid found in high concentrations in Jacobaea vulgaris. Toxic to a number of mammals (grazing stock such as cows and horses particularly susceptible). Fresh plants tend to be avoided, but problems can occur when ragwort ends up dried in hay or silage. Senecionine is hepatotoxic. Some insects preferentially feed on plants containing high levels of pyrrolizidine alkaloids such as senecionine. The alkaloids accumulate in the skin of the caterpillars, protecting them from predation
Alkaloids for defense?
Alkaloids are found in animals:
Puffer fish
- Family: Tetraodontidae (over 30 species)
- Weapon of choice: Tetrodotoxin
Golden poison frog
- Phyllobates terribilis
- Weapon of choice: multiple different alkaloids including Batrachotoxin
the structure of alkaloids?
Contain nitrogen, usually in a heterocyclic ring
Basic (alkaline) in nature; alkaloids form salts with acids – e.g. morphine hydrochloride
what are the Classes of Alkaloids?
Quinoline: eg quinine
Indole: e.g. strychnine, physostigmine, ergot alkaloids (including LSD), vinca alkaloids
Tropane: e.g. cocaine, atropine
Isoquinoline: e.g. morphine, codeine
Bisbenzylisoquinoline: e.g. tubocurarine
Pyridine: e.g. nicotine
Miscellaneous: e.g. caffeine, ephedrine, colchicine
give examples of uses of Quinoline Alkaloids
Quinine: An antimalarial from which newer drugs (e.g. chloroquine, mefloquine) have been developed. Also acts as an anti-arrhythmic, so avoid in heart disease. Used in ‘tonic water’
Quinidine: closely related to quinine - a more potent anti-arrhythmic
Derivatives of quinine are used as antimalarials
Chloroquine - Sometimes used in amebiasis, rheumatoid arthritis and lupus
Mefloquine (or Lariam®) - side effects can include depression and anxiety
what motifs do Quinoline Alkaloids have?
they all contain a “quinoline” group
what motifs do Indole Alkaloids have?
These structures contain an indole
what motifs do Tropane Alkaloids have?
These structures contain tropane
where do Isoquinoline Alkaloids come from?
Alkaloid examples?
toxicity?
Papaver somniferum (Papaveraceae)
Opium, the dried latex from the unripe capsule (fruit)
Seeds used in cooking and for oil
Analgesic (pain killer)
Alkaloid examples: morphine, codeine, Thebaine
Toxicity: depends - seeds and oil safe, alkaloids not!
what motifs do Isoquinoline Alkaloids have?
Alkaloids in this class contain isoquinoline, or derivatives of isoquinoline (such as benzoisoquinoline)
what are different Isoquinoline Alkaloids used for?
Papaverine: a smooth muscle relaxant, used for male impotence
Morphine: a strong pain-killer – can be acetylated to diamorphine (heroin) using acetic anhydride
Thebaine: toxic, can be converted to codeine, also used as a source of Bentley compounds, such as etorphine, used as veterinary sedative and for euthanasia
Codeine: also an analgesic, and used for coughs and to treat diarrhoea
What is meant by “biosynthetic precursor”?
In cells, biological molecules are built up in from smaller precursors. Small molecules are gradually elaborated into larger and more complex structures. A biosynthetic precursor is a molecule which goes on to become another important biological molecule. You can often see parts of the structure of the biosynthetic precursor in the final product.
The majority of opioid alkaloids used as therapeutics (or their precursors) are still extracted from plants (or other natural sources). Suggest reasons for this.
Opioid alkaloids have very complex structures which are difficult to make synthetically, so it is easier to extract them from natural sources. In addition, plants produce very large quantities of opioid alkaloids, so it is easy to extract a large quantity of the desired products.
Alkaloids have basic nitrogen atoms. How might this aid the extraction of material from natural materials?
As the nitrogen atom is basic, it can be protonated and deprotonated easily – so it makes it easy to extract from other material, as depending on whether it is protonated or not, they can be extracted into water or organic solvents selectively.
Outbreaks of ergotism have been documented in historical sources, but the descriptions of the symptoms in these records can often differ. Suggest reasons for this.
Ergotism arises from eating grain contaminated with fungi which produces a large number of different alkaloids. It is likely that different alkaloids in this group have different effects, so the overall clinical presentation of the resultant disease (and hence the description) will differ if people have consumed larger quantities of one alkaloid in the mixture over another. These differences can arise from different strains of fungi or different environmental conditions influencing the alkaloids produced.
Papervarine is often administered as the hydrochloride salt. The structure of papervarine is shown below.
Convert the molecule to the hydrochloride salt form.
TTX has been reported to be found in some types of shellfish as well as in pufferfish. What does this suggest about the biosynthesis of TTX?
This could suggest a couple of things, but they are both related to the same point – that there is a similarity between the shellfish and the pufferfish.
This could be an intrinsic biological similarity – that they share a biosynthetic pathway.
It could also be an environmental similarity – for example, they could both derive the toxin in the same way from an external source (such as a shared food stuff).
a) . By injection, the fatal dose of TTX in mice has been reported to be around 8 µg per kg. Can you estimate how much TTX would be fatal to a person if were administered by injection?
b) . When we’ve been carrying out these calculations, we’ve had to make some assumptions about the data. What are some of the limitations of the data we’ve used to form our conclusions?
8 µg per kg x 75 kg = 600 µg
600 µg ÷ 1000 = 0.6 mg
There are a few here.
- You might consider if the data for mice would be equivalent to the data in humans?
- Do mice respond to TTX in the same way a person would?
- We estimated an average weight for a person too.
- Would all people respond to a toxin in the same way?
