Phytochemistry

• Phytochemistry


  Isolation and identification of compounds from plants, i.e. the chemistry of plants: it looks at what types of compounds are found in plants, how they're biosynthesised and the potential uses of the compounds that can be isolated from different plant materials
• Pharmacognosy


  Scientific basis for the use of plants in pharmacy
• Ethnopharmacognosy


  (Historical) medicinal use of plants by different societies around the world
• Traditional medicine


  Medicines, often from natural sources, used by traditional healers in a community
• Biochemical processes in plants


  • Primary metabolism (production of molecules common across many forms of life e.g. carbohydrates, proteins, nucleic acids)
  • Secondary metabolism (production of compounds unique to certain species or organisms)
• Secondary metabolites


  Compounds of most interest for their medicinal potential, produced for reasons e.g. defence or as by-products from other processes
• Plants are a major source of drugs — over 25% of current drugs contain compounds derived from plants — and many more come from drug development programmes started by natural product investigation
• The WHO estimates 75-80% of people in developing countries rely on plant-based medicine for primary health care
• Herbal medicines/functional foods (nutraceuticals)


  Natural products consumed in the Western world
• Botanicals


  Whole plant extracts licensed for medicinal use in the USA
• Herbal medicines in the UK


  Can be recommended and sold by untrained individuals; pharmacists need to be familiar with the remedies available and be able to give accurate advice if necessary
• Natural products


  Fall into one of two categories: food or drugs
• Regulations for using natural products as drugs in the EU


  1. If a particular plant has been used for a very long time, e.g. 10s or 100s of years, without any negative side effects, it can be deemed to be safe

  2. If the plant extract is being used recently or for the first time, there's very stringent procedure it needs to undergo to prove it's safe and does what it says it does
• The laws governing drugs have stringent requirements ensuring that manufactures demonstrate both safety and efficacy
• In Europe, the law is such that anybody claiming therapeutic benefit for a product must comply with the full drug legislation
• In the UK, exemptions have been made for over 300 substances to allow the continued sale of traditionally used herbal medicines
• These exempted substances merely had to have their safety and efficacy shown by their established use
• Using plants as drugs

  An entire plant extract is used: the patient is given a mixture of compounds/all the compounds in the extract without necessarily knowing which compound is the active one
• Using plants as a basis for drug discovery

  Bioassay directed fractionation is used: extract is tested to find if it's active and then chromatography is used to separate it into different fractions. Fractions are tested to determine which one is active. Once that's determined, it's separated into its individual components and test the individual compounds to determine which one is actually active
• Often, the natural extract or the active product isolated from the extract can be quite complex and difficult to synthesise, so it may need to be chemically modified to make it more bioavailable or to more easy to dose the patient
• Organs where useful natural products are most commonly found


  • Aerial parts or herb (herba)
  • Leaf (folia)
  • Flower (flos)
  • Fruit (fructus)
  • Bark (cortex)
  • Root (radix)
  • Rhizome (rhizoma)
  • Bulb (bulbus)
• Drug Extraction


  1. Dry either the entire plant or selected organs

  2. Extract products like oils, gums and resins (usually mixtures of compounds)

  3. Extract compounds chemically from the plant material
• Chemical extraction process


  1. Dry and crush/chop plant material to increase surface area

  2. Use a suitable solvent to extract compounds, often hot solvent in a soxhlet apparatus or supercritical carbon dioxide

  3. Further purify initial extracts by additional extractions or chromatography

  4. Identify the isolated product using spectroscopic methods
• Supercritical carbon dioxide extraction


  Very environmentally friendly, the CO2 can be evaporated after extraction. Allows extraction of compounds of different polarities by adjusting temperature and pressure. Downside is expensive apparatus
• Constituents of crude plant extracts

  • Fatty acids
  • Waxes
  • Volatile oils (essential oils)
• Fatty acids


  Important components of plant oils, generally found in all organisms. Can be saturated or unsaturated. Often found as esters, especially glycerides. Sodium salts of fatty acids are soaps. Important in formulation of drugs and cosmetics
• Waxes


  Mostly esters of fatty acids with long chain alcohols

  
• Volatile oils (essential oils)


  Have lower boiling points than fixed oils, can be isolated by steam distillation. Used for their antibacterial, therapeutic, flavour or perfume properties. Mainly composed of phenyl propenes and monoterpenes
• Monoterpenes


  Major constituents of volatile oils, illustrate the chemical variety which can occur in different species using common chemical starting materials. All have 10 carbon atoms, biosynthesised from two 5-carbon units related to isoprene
• Volatile Oils (aka Essential Oils)

  Oils with lower boiling points than fixed oils, can be isolated by steam distillation, used for antibacterial, therapeutic, flavour or perfume properties
• Fixed Oils


  Oils with different chemical composition compared to volatile oils
• Major constituents of volatile oils


  • Phenyl propenes (e.g. cinnamaldehyde)
  • Monoterpenes
• Monoterpenes


  Major constituents of volatile oils, have 10 C atoms in their structures, come from two C5 units related to isoprene
• Monoterpene biosynthesis


  1. OPP is a good leaving group and can be displaced by a nucleophile

  2. Nucleophile attacks the carbon next to the PP group

  3. PP group leaves, giving the nucleophile attached to the carbon
• DMAPP and IPP


  Biosynthetic precursors based on isoprene, form the entire range of terpene compounds
• Formation of geranyl PP

  1. OPP leaves from DMAPP, forming a cation

  2. IPP has a double bond, which attacks the cation, forming a bond

  3. Hydrogen is lost to reform the DB and produce geranyl PP

  
• Compounds formed from geranyl PP


  • Citronellol (rose oil)
  • Menthol
  • Thymol

  
• Formation of limonene


  1. Bond rotation from cis to trans

  2. Carbocation is in close proximity to the electron-rich DB, allowing for nucleophilic attack

  3. Hydrogen ion can then be lost to give a double bond

  
• Sesquiterpenes


  Natural products derived from farnesyl PP, which has 15 C atoms

  
• Artemisinin has been used in Chinese traditional medicine as a treatment for malaria