Natural product chemistry I Flashcards
What is the historical significance of natural products in medicine, and what are drug leads?
Historical Role: Core of medicines and a significant source of drug leads.
Drug Leads Definition: Compounds with potential for development into medicines well
Where was Paclitaxel initially isolated, and what is its market name
Initially isolated from the bark of the Pacific yew tree, Taxus brevifolia.
Market Name: Paclitaxel marketed as Taxol.
How are natural products produced in an eco-friendly manner, and what are the methods mentioned?
Production of natural products is eco-friendly and can be achieved by growing plants or fermenting micro-organisms.
Natural products
Definition: Bulk substances from nature, including crude plant material, foodstuffs, and plant extracts like myrrh and frankincense.
What are the initial steps in the drug discovery process, and what is the purpose of biomass collection?
Biomass (plant, microbe, marine organism) collected, dried, and extracted using organic solvent.
Extract screened in a bioassay to assess biological activity
How is the assessment of biological activity divided, and what are the two formats mentioned?
Low throughput screening.
High throughput screening.
Describe the process of bioassay guided isolation and its purpose.
Active extracts fractionated using chromatographic techniques.
Biological activity checked during each stage until a pure active compound is obtained
What steps are involved in evaluating a lead compound, and why is structure elucidation important?
Ongoing biological evaluation.
Structure elucidation for three-dimensional structure determination.
Establish novelty, chemical class, and prior reports of biological activity.
What is the next step after lead compound evaluation, and what aspects are assessed during this step?
Extensive in vivo studies to establish activity, toxicity, and efficacy.
Classes of natural products
The polyketides
Shikimic-acid-derived natural products
The terpenes
The glycosides
The alkaloids
What are polyketides mainly derived from?
Polyketides are mainly acetate (C2)-derived metabolites
Which filamentous bacteria is known for producing structurally diverse polyketides?
Streptomyces
Name some examples of polyketide groups.
Fatty acids, glycerides, tetracyclines, griseofulvin, erythromycin A, statins.
How does the biosynthesis of polyketides occur?
The biosynthesis involves the condensation of malonyl-CoA with acetyl-CoA, to produce long-chain fatty acids.
What is the mechanism involved in forming these compounds (polyketides)?
Claisen reaction mechanism
What are glycerides?
Glycerides are fatty acid esters of propane-1,2,3-triol (glycerol).
How can glycerides be converted into soaps?
Glycerides can be converted into soaps by a strong base (NaOH), as they are saponifiable natural products
Why are fatty acids important in pharmacy?
Fatty acids are crucial as formulation agents and vehicles in pharmacy.
Give an example of a fatty acid found in olive oil.
Oleic acid, which is widespread in plants, is a major component of olive oil from the olive tree Olea europaea.
What is the main purgative ingredient of castor oil?
Ricinoleic acid is the main purgative ingredient of castor oil from the seeds of Ricinus communis.
Which acid is a constituent of linseed oil?
α-Linolenic acid is a constituent of linseed oil from Linum usitatissimum.
What is the origin of tetracycline?
Tetracycline comes from mutants of Streptomyces aureofaciens.
What is the spectrum of activity for tetracycline antibiotics?
Tetracycline antibiotics have a very broad spectrum of activity against Gram-positive and Gram-negative bacteria, spirochetes, mycoplasmae, rickettsiae, and chlamydiae.
How are minocycline and doxycycline produced?
Minocycline and doxycycline are produced semi-synthetically from natural tetracyclines
What is the source of erythromycin A?
Erythromycin A is a complex polyketide from Saccharopolyspora erythrea, a filamentous bacterium originally classified in the genus Streptomyces.
What is the composition of the therapeutic antibiotic marketed as erythromycin?
The therapeutic antibiotic erythromycin is marketed as a mixture containing predominantly erythromycin A, with small amounts of erythromycins B and C.
What medical conditions is erythromycin commonly used to treat?
Erythromycin is used to treat Legionnaire’s disease and respiratory tract infections in patients allergic to penicillin.
What is the source of griseofulvin?
Griseofulvin, also known as Grisovin, is a polyketide antibiotic derived from the fungus (mould) Penicillium griseofulvum
What type of infections is griseofulvin recommended for?
Griseofulvin is recommended for the systemic treatment of fungal infections of the skin, hair, nails, and feet caused by fungi belonging to the genera Trichophyton, Epidermophyton, and Microsporum.
What is the primary function of statins?
Statins are used to lower the production of cholesterol.
Provide examples of statins and their original sources.
Mevastatin, initially isolated from cultures of the fungi Penicillium citrinum and Penicillium brevicompactum,
Lovastatin, isolated from Monascus ruber and Aspergillus terreus.
What is another name for shikimic acid?
Shikimic acid is sometimes referred to as shikimate.
What role does shikimic acid play in biosynthesis?
Shikimic acid serves as a simple acid precursor for various natural products and aromatic amino acids, including phenylalanine, tyrosine, and tryptophan.
Name some classes of compounds derived from shikimic acid.
Phenylpropenes, lignans, coumarins, flavonoids, and tannins
Biosynthesis of propylene
Propylene is biosynthesized into cinnamic acid through the oxidation of phenylalanine, catalyzed by the enzyme phenylalanine ammonia lyase.
How is cinnamaldehyde, a major component of cinnamon oil, derived?
is obtained by reducing cinnamic acid.
What is the hallucinogenic component in nutmeg?
Myristicin, a component of nutmeg (Myristica fragrans), is known for its hallucinogenic properties.
Name the major components of star anise, aniseed, and fennel.
Safrole and trans-anethole are the major components of star anise (Illicium verum), aniseed (Pimpinella anisum), and fennel (Foeniculum vulgare). They are commonly used as essential oils
What enzyme is involved in the biosynthesis of cinnamic acid?
the enzyme phenylalanine ammonia lyase.
What are lignans, and how are they formed?
Lignans are low molecular weight polymers formed by the coupling of two phenylpropene units. A common precursor of lignans is cinnamyl alcohol.
Name some compounds derived from Podophyllum peltatum and Podophyllum hexandrum used in treating warts.
Podophyllotoxin, 40-demethylpodophyllotoxin, α-peltatin, and β-peltatin, used in the treatment of warts by North American Indians
Why is podophyllotoxin not used clinically despite its therapeutic properties?
Podophyllotoxin is highly toxic
How are coumarins derived, and what is their origin?
Coumarins are shikimate-derived metabolites formed when phenylalanine is deaminated and hydroxylated to trans-hydroxycinnamic acid, which readily converts to the cis form and undergoes a lactonization reaction to form coumarin itself
What are phytoalexins?
Phytoalexins are coumarins synthesized de novo by plants.
When are phytoalexins produced by plants?
Phytoalexins are produced by plants following infection by a bacterium or fungus.
Provide an example of a phytoalexin.
Aesculetin is an example of a phytoalexin, occurring in horse chestnut (Aesculus hippocastanum).
How is aesculetin used in phytotherapeutic preparations?
used in phytotherapeutic preparations to treat capillary fragility.
What are psoralens?
Psoralens are coumarins with a furan ring.
Where are psoralens typically found?
Psoralens are typical of the citrus (Rutaceae) and celery (Apiaceae) families.
What protective role do psoralens play in plants?
Psoralens may be produced by plants as a protection mechanism against high doses of sunlight.
How are some coumarins, including psoralens, utilized?
Some coumarins, including psoralens, are formulated into sunscreens and cosmetics for their protective properties against sunlight
How have preparations with psoralens been used in the context of the disease vitiligo?
Preparations using apiaceous and rutaceous plants containing psoralens have been used to promote skin pigmentation in the disease vitiligo
How are flavonoids produced?
Flavonoids are products of mixed biosynthesis, consisting of units derived from both shikimic acid and polyketide pathways
What ecological role do flavonoids play in nature?
Flavonoids have high ecological importance in nature, serving as color attractants to insects and birds to aid in plant pollination.
Why are flavonoids considered to have dietary significance?
Flavonoids, such as quercetin, are strongly antioxidant, contributing to their dietary significance. They are used to reduce the effects of poisoning by fungi of the genus Amanita.
What is the composition of tannins?
Tannins comprise water-soluble polyphenolic acids
How are hydrolysable tannins formed?
Hydrolysable tannins are formed by the esterification of sugars (e.g., glucose) with simple phenolic acids that are shikimate-derived, such as gallic acid.
What is another name for non-hydrolysable tannins?
Non-hydrolysable tannins are sometimes referred to as condensed tannins.
What key feature of tannins makes them useful in various applications?
A key feature of tannins is their ability to bind to proteins, making them useful for tanning leather, clarifying beer, and as astringent preparations in pharmacy.
Provide an example of a tannin used in a topical preparation for cold sores.
Tannic acid is used as a topical preparation for cold sores.
