Terrestrial Natural Product Chemistry STK 31003

Terrestrial Natural Product Chemistry (STK 31003)

• This course focuses on terrestrial natural product chemistry.

Primary Metabolites

• Ubiquitous
• Essential for plant growth and development
• Examples include lipids, nucleotides, amino acids, organic acids, and sugars.

Secondary Metabolites

• Found in limited taxonomic groups
• Functions are often unclear
• Examples include saponins, flavonoids, steroids, and alkaloids.

Why Plants Produce and Accumulate Natural Products

• Potential overflow of primary metabolism products
• Natural selection for adaptation
• Defense mechanisms (e.g., phytoalexins and phytoanticipins)
• Allelopathy: suppressing the growth of other plants near them. Some plants release chemicals from leaves as they decompose, or from roots
  • Examples include Long pepper (Piper longum), Neem (Azadirachta indica), and Sunflower (Helianthus annuus).

Phytoalexins

• Low molecular weight antimicrobial compounds.
• Produced by plants in response to biotic and abiotic stresses.
• Crucial part of plant defense mechanisms controlling invading microorganisms.

Phytoanticipins

• Low molecular weight antimicrobial compounds.
• Present in plants prior to microbial attack.
• Can be produced after infection from preexisting constituents.

Why Study Secondary Metabolites/Natural Products?

• Direct use as drugs:
  • Examples include morphine (analgesic), codeine (antitussive), quinine (antimalarial), vinblastine and vincristine (anticancer drugs).
• Starting material for useful drugs synthesis:
  • Steroid hormones, such as adrenal cortex hormones, are synthesized from steroidal sapogenins found in plants.

Chemotaxonomy

• Classifying plants based on their chemical compounds.
• Plants with rare chemical distributions are useful for classification.
• Examples: isoflavones in legumes and iridaceae; alkaloids in Rauwolfia and Catharanthus (Apocynaceae); cardenolides in Nerium, Thevetia and Strophantus (Apocynaceae).

Classification of Natural Products

• Based on chemical structures (e.g., open-chain aliphatic, alicyclic, aromatic, heterocyclic compounds).
• Based on physiological activities (e.g., hormones, vitamins, antibiotics).
• Based on taxonomy (e.g., family, genus).
• Based on biogenesis (pathways of production).

Classification Based on Chemical Structures

• Formal classification based on molecular skeleton.
  • Open-chain aliphatic or fatty compounds (fatty acids, sugars).
  • Alicyclic or cycloaliphatic compounds (terpenoids, steroids, alkaloids).
  • Aromatic or benzenoid compounds (phenolics, quinones).
  • Heterocyclic compounds (alkaloids, flavonoids, nucleic acid bases).
• Many compounds fall into multiple classes (e.g., geraniol, farnesol, squalene, thymol).

Classification Based on Physiological Activities

• Classifying based on observed physiological effects.
• Some closely related compounds may have similar activities despite having different structures (e.g., morphine, penicillin G, prostaglandins).
  • Examples: hormones, vitamins, antibiotics, mycotoxins.

Prostaglandins

• Hormone-like substances regulating various body functions, including smooth muscle contraction/relaxation, blood vessel dilation/constriction, blood pressure control and inflammation modulation
• Derived from arachidonic acid; used as examples.

Prostaglandins

• Hormone-like substances regulating various body functions, including smooth muscle contraction/relaxation, blood vessel dilation/constriction, blood pressure control and inflammation modulation
• Derived from arachidonic acid

Classification Based on Taxonomy

• Comparing plant morphology and taxonomy to classify compounds.
• Compounds from the same family or genera have limited distributions.
• Examples include opium alkaloids (e.g., morphine, thebaine, codeine, narcotine).
• Other examples are iboga alkaloids and ergot alkaloids.

Classification Based on Biogenesis

• Classifying based on the hypothetical or confirmed biosynthesis pathways.
• Compounds sharing similar pathways are grouped.
• The isoprene rule (proposed by Ruzicka) states that terpenoids are built from isoprene units.
• Examples include nerol, santonin, and oleanolic acid.

Biosynthesis Pathways

• Mevalonate Pathways: Synthesis of terpenoids/steroids
• Examples: limonene, camphor, pinene, farnesol, squalene, cholesterol, cortisone
• Shikimate Pathways: Synthesis of aromatic amino acids and phenyl compounds
• Examples: tryptophan, phenylalanine, tyrosine, eugenol, lignan, lignin
• Polyketide/acetogenin/acetate-malonate pathways: Aromatic compounds (e.g., quinones, depside/depsidone, coumarins, xanthones)
• Alkaloids Pathways: Alkaloid synthesis utilizing amino acids, Mannich reaction, and phenol oxidation and coupling

Main Building Blocks for Carbon and Nitrogen in Natural Products

• I: Acetyl-CoA and malonyl-CoA (C2 unit) → Polyketides
• II: Shikimic acid → Aromatic amino acids and phenolics.
• III: Mevalonic acid → Prenyl units → Terpenoids and isoprenoids.
• IV: Amino acids → Alkaloids
• V: S-5'-deoxyadenylmethionine → C₁

Starting Materials for Biosynthesis

• Photosynthesis (erythrose 4-phosphate → Glucose → Starch)
• Glycolysis (Phosphoenol pyruvate)
• acetyl-CoA (Mevalonate pathway), amino acids (shikimate/other pathways)

Additional pathways

• Additional biosynthetic diagrams are presented involving the interconnections between pathway inputs and common starting materials for the synthesis of a number of important groups of natural products, such as alkaloids, flavonoids, terpenoids, and steroids.

Chemical structures of Examples

• Several chemical structures of relevant examples are included for reference.

Explore the fascinating world of terrestrial natural product chemistry in this quiz. Focused on primary and secondary metabolites, you'll learn about their roles in plant growth, defense mechanisms, and ecological interactions. Test your knowledge on the examples and functions of these essential compounds.