Introduction to Natural Products Chemistry NFNF1813

Introduction to Natural Products Chemistry

• Course offered by Assoc. Prof. Dr. Khairana Husain
• Course code: NFNF1813

Medicinal Plants

• Defined as plants containing properties or compounds usable for therapeutic purposes, or those synthesizing metabolites for useful drugs (WHO 2008).

Medicinal Agents from Natural Sources

• Categorized into:
  • Fully natural
  • Semisynthetic
  • Fully synthetic
• Examples include:
  • Clavulanic acid
  • Aspirin
  • Pethidine

Importance of Medicinal Plants

• 80% of the global population relies on medicinal plants.
• In Western countries, roughly 35% of prescribed medications have natural origins.
• Over 50% of over-the-counter (OTC) drugs originate from medicinal plants.

Major Killer Diseases Worldwide

• AIDS: 3.1 million deaths annually, 5.5 million new cases.
• Tuberculosis: 2 million deaths annually, 8 million new cases.
• Diarrheal Diseases: 1.9 million deaths.
• Malaria: 1 million deaths annually, 300-500 million new cases.
• Hepatitis B Virus: 1 million deaths annually, 10-30 million new cases.
• SARS (2004): 8,096 cases, 774 deaths (648 in HK/China).
• Tobacco-related: 3.5 million deaths (primarily cancer and lung diseases).
• COVID-19: unknown death toll.

Some Issues for Drug Discovery

• Major global diseases lack effective treatments.
• Drug resistance (anti-infective, anti-cancer, antimalarial, etc.) is increasing.
• New diseases are emerging (SARS, avian flu, Marburg virus, COVID-19, etc.).
• The cost of developing a new drug is at least $800 million (unaffordable in most parts of the world).
• The role of natural products as established pharmaceuticals is well-acknowledged.

Medicinal Plants as a Bio-Resource

• A rich source of materials for:
  • Traditional medicine
  • Modern medicines
  • Nutraceuticals
  • Food supplements
  • Folk medicines
  • Pharmaceutical intermediates
  • Chemical entities for synthetic drugs

Natural Products Chemistry (Classification)

• Shikimic acid-derived: phenylpropenes, lignans, coumarins, flavonoids, tannins
• Polyketides: fatty acids, glycerides, tetracyclines, griseofulvins, erythromycin A, statins
• Terpenes: monoterpenes, sesquiterpenes, diterpenes, triterpenes, tetraterpenes
• Glycosides: cyanide glycosides, glucosinolates, cardiac glycosides, anthraquinone glycosides
• Alkaloids: pyridine, piperidine, pyrrolizidine, phenylalkylamine, quinoline, isoquinoline, indole, tropane, xanthine, imidazole

Types of Phytochemicals

• Oils and Fats
• Prostaglandins
• Vitamins
• Steroids
• Lignins
• Proteins
• Antibiotics
• Mycotoxins, etc.
• Terpenoids
• Alkaloids
• Flavonoids
• Carbohydrates
• Lignans
• Nucleic acid
• Pigments
• Pheromones

Metabolic Pathways of Natural Products

• Metabolic pathways connecting various natural product classes, showcasing their biosynthesis processes.

Biosynthetic Pathways of Secondary Metabolites

• Key pathways like acetate, shikimate, mevalonate, and deoxyxylulose phosphate
• Leading to the synthesis of various secondary metabolites.

Natural Products and Ecology

• Plants, fungi, bacteria, lichens, insects, and animals produce a diverse range of organic compounds.
• Examples of these compounds and their functions.

Systematic Approach of Natural Products Drug Discovery

• A systematic process that begins with plant, microbes, or marine biomass,
• Followed by extraction steps, screenings, bioassays, isolations, structure elucidation, large-scale isolation, chemical modifications, in-vivo studies, and clinical trials.

A Road Map for Medicinal Plant Development

• A comprehensive approach outlining steps required for identifying and developing new medicines from medicinal plants (considerations for safety, toxicity, testing, etc.).

Some Milestones in Natural Products Chemistry

• Historical discoveries of key natural products like morphine, strychnine, and quinine, including isolation, structure elucidation, and synthesis.

Detection Methods

• General chemical reagents (ferric chloride : dark blue to dark green color)
• Semi-specific chemical reagents (Bate-Smith reaction: tannins, Cyanidine test: flavonoids, Bornträger reaction: anthracenosides)

Tests for Alkaloids

• Most alkaloids precipitate from neutral or slightly acidic solutions using:
  • Dragendorff's reagent (potassium bismuth iodide): orange precipitate.
  • Mayer's reagent (potassium mercuric iodide): cream precipitate.
  • Wagner's reagent (iodine in potassium iodide): red-brown precipitate.
  • Hager's reagent (picric acid): yellow precipitate.

Extraction of Phenolics in a Neutral Medium

• Process details for extracting phenols from plant materials. Includes use of hydroalcoholic solutions, reduced pressure, organic solvents, aqueous solutions, and isolation of glucosides.

General Extraction of Alkaloids from Powdered Plants

• Plant material and solvent; organic solvent dissolving alkaloids and impurities; concentration; acidification; and alkalinization steps leading to separation (alkaloid-containing solution and a neutral organic layer).

General Isolation Strategy of Natural Products

• Ground plant; solvent extraction yields crude plant extract; following fractionation, chromatography; (crude compound purification); yields a pure compound; and structure determination steps for determining the chemical structure of the pure compound.