OU-M. Pharmacy (Pharmaceutical Chemistry) Chemistry of Natural products 1st Semester Model Paper 2024

Time: 3 Hours | Max. Marks: 75

Note: Answer any five questions. All questions carry equal marks.

1. (a) Define Alkaloids and write the general methods to determine the structure of Alkaloids. (8+7)

Alkaloids: Alkaloids are a group of naturally occurring organic compounds that mostly contain basic nitrogen atoms. They are derived from plants, fungi, and some animals. Alkaloids often have potent biological effects, and examples include morphine, quinine, nicotine, and caffeine. They typically have a bitter taste and can be toxic in high doses.

Methods to Determine the Structure of Alkaloids:

  1. Isolation and Purification: Alkaloids are isolated using solvents like ethanol, chloroform, and ether. Purification is done via chromatography methods (e.g., column chromatography).
  2. Chemical Tests: Specific tests (e.g., Dragendorff’s reagent) confirm the presence of alkaloids.
  3. Spectral Analysis:
    • UV/Vis Spectroscopy: Identifies conjugated double bonds and chromophores.
    • IR Spectroscopy: Helps detect functional groups (amine group, hydroxyl group).
    • NMR Spectroscopy: 1H-NMR and 13C-NMR give detailed insights into the structure by showing the positions of protons and carbon atoms.
    • Mass Spectrometry: Provides the molecular weight and fragmentation patterns.
  4. X-ray Crystallography: If the alkaloid can be crystallized, this method is used to determine its 3D structure.

1. (b) Write the special isoprene rule in terpenoids. (7 Marks)

Isoprene Rule in Terpenoids: The isoprene rule helps determine the structure of terpenoids, which are naturally occurring compounds made from isoprene (C5H8) units. The rule states that:

  • Terpenoids are constructed by linking isoprene units (C5H8) through head-to-tail or tail-to-tail linkages.
  • The number of isoprene units determines the terpene class:
    • Monoterpenes (C10H16) contain 2 isoprene units.
    • Sesquiterpenes (C15H24) contain 3 isoprene units.
    • Diterpenes (C20H32) contain 4 isoprene units.
    • Triterpenes (C30H48) contain 6 isoprene units.
    • Tetraterpenes (C40H64) contain 8 isoprene units.

These terpenoids exhibit diversity due to the various ways isoprene units can be joined.

2. Write the structural elucidation of any two drugs. (8+7)

(i) Morphine (Opioid Analgesic):

  • Molecular Formula: C17H19NO3
  • Structure: Morphine consists of a fused benzene ring and cyclohexene ring. It contains a nitrogen atom in the piperidine ring, hydroxyl groups, and a phenolic -OH.
  • Spectral Data:
    • 1H-NMR: Aromatic protons at 5.5 ppm, -OH group at 3.4 ppm, and broad signal at 1.8-2.5 ppm (methylene and methine).
    • 13C-NMR: Peaks at 120-140 ppm (aromatic carbons), 50-60 ppm (methylene groups).
    • IR: OH stretch at 3400 cm-1, C-H bending at 1480 cm-1, C=O stretch at 1700 cm-1.

(ii) Quinine (Antimalarial Drug):

  • Molecular Formula: C20H24N2O2
  • Structure: Quinine consists of a quinoline ring system fused to a quinuclidine ring. It contains a tertiary amine and a hydroxyl group.
  • Spectral Data:
    • 1H-NMR: Aromatic protons at 7.5-8.5 ppm, -OH group at 3.9 ppm, methylene groups at 3.3-4.0 ppm.
    • 13C-NMR: Peaks at 120-140 ppm for aromatic carbons, 50-60 ppm for aliphatic groups.
    • IR: Strong OH stretch at 3400 cm-1, aromatic C-H stretch at 2950 cm-1, C=O stretch at 1700 cm-1.

3. Write how the natural products act as leads in the following classes of drugs:

(i) Antimalarial Drugs and Analogues (8 Marks)

  1. Quinine: Derived from the bark of Cinchona trees, quinine is the first effective treatment for malaria. It inhibits the parasite’s ability to digest hemoglobin.
  2. Artemisinin: A derivative of the plant Artemisia annua, artemisinin is highly effective against malaria. It works by generating reactive oxygen species that damage the malaria parasite.
  3. Chloroquine: This synthetic analogue of quinine interferes with the malaria parasite’s ability to process hemoglobin.

Analogues: Drugs like artesunate and artemether are developed from artemisinin for enhanced effectiveness in treating drug-resistant malaria.

(ii) Cardiovascular Drugs (7 Marks)

  1. Digitalis (Digoxin): Extracted from foxglove (Digitalis purpurea), it is used in heart failure. It works by inhibiting the Na+/K+ ATPase pump, increasing intracellular calcium and enhancing heart contractility.
  2. Nitroglycerin: A nitrate used as a vasodilator. It releases nitric oxide, relaxing smooth muscle in blood vessels to improve oxygen delivery to the heart.
  3. Reserpine: An alkaloid from Rauwolfia serpentina that lowers blood pressure by depleting norepinephrine and reducing sympathetic activity.

Analogues: Drugs like isosorbide dinitrate and beta-blockers have been developed from these natural leads to improve cardiovascular health.

4. Write the structural characterization of the following compounds using IR, 1H-NMR, 13C-NMR, and Mass spectral data (Write approximate values)

(i) Quercetin:

  • IR: OH stretch at 3400 cm-1, aromatic C-H stretch at 3050 cm-1, C=O stretch at 1650 cm-1.
  • 1H-NMR: Aromatic protons at 6.0-7.5 ppm, hydroxyl protons at 12 ppm.
  • 13C-NMR: Signals around 160 ppm for C=O, 120-140 ppm for aromatic carbons.
  • Mass Spectrum: M+ at 302 m/z.

(ii) Vitamin D:

  • IR: C-H stretch at 2950 cm-1, C=O stretch at 1700 cm-1.
  • 1H-NMR: Methyl groups at 0.8-1.0 ppm, olefinic protons at 5.2-6.0 ppm.
  • 13C-NMR: Methyl groups at 30-40 ppm, olefinic carbons at 125-150 ppm.
  • Mass Spectrum: M+ at 384 m/z.

(iii) Digoxin:

  • IR: OH stretch at 3400 cm-1, C=O stretch at 1700 cm-1, aromatic C-H stretch at 3000 cm-1.
  • 1H-NMR: Methylene protons at 0.8-2.5 ppm, aromatic protons at 6-8 ppm.
  • 13C-NMR: Peaks around 30-50 ppm for alkyl groups, 160 ppm for C=O.
  • Mass Spectrum: M+ at 780 m/z.

5. Write down the active constituents present in the following crude drugs with structures (minimum three from each crude drug)

(i) Curcuma longa:

  • Curcumin: A polyphenolic compound responsible for the yellow color. Structure: Bis-phenolic structure with methoxy groups.
  • Demethoxycurcumin: Similar to curcumin, but without one methoxy group.
  • Bisdemethoxycurcumin: The compound with no methoxy groups.

(ii) Pterocarpus marsupium:

  • Pterocarpin: A flavonoid-like compound.
  • Marsupin: A compound found to exhibit anti-diabetic effects.
  • Pterocarpuside: Another constituent that helps in managing blood sugar levels.

(iii) Gymnema sylvestre:

  • Gymnemic Acids: The main bioactive constituents with anti-sweet properties.
  • Gymnema Saponins: Known for their hypoglycemic effects.
  • Gymnemagenin: The aglycone form of gymnemic acid, contributing to its pharmacological action.

6. (a) Write a note on chemistry and physiological significance of the following vitamins:

(i) Vitamin A:

  • Chemistry: Vitamin A, also known as retinol, is a fat-soluble vitamin. It is derived from carotenoids in plants and is essential for vision, immune function, and cell growth.
  • Physiological Significance: It supports vision (especially in low light), immune function, and skin health.

(ii) Vitamin B12:

  • Chemistry: Vitamin B12 (Cobalamin) is a water-soluble vitamin containing cobalt. It plays a crucial role in DNA synthesis and red blood cell formation.
  • Physiological Significance: It is essential for the functioning of the nervous system and the production of red blood cells.

(iii) Vitamin C:

  • Chemistry: Vitamin C (ascorbic acid) is a water-soluble vitamin with antioxidant properties.
  • Physiological Significance: It is important for collagen synthesis, wound healing, and the maintenance of cartilage, bones, and teeth.

(b) Write the structural elucidation of Quercetin:

Structure of Quercetin: Quercetin is a flavonoid with a chemical structure composed of a benzene ring (A), a pyrone ring (C), and a hydroxyl group (-OH) at several positions on the rings.

7. (a) Discuss the chemistry of sapogenins and cardiac glycosides. (9+6)

Sapogenins: Sapogenins are aglycones of saponins. They are steroid-like compounds found in plants like ginseng and soybeans. Sapogenins can be classified as spirostanes or furostanes based on the presence of ring structures.

Cardiac Glycosides: Cardiac glycosides, such as digoxin and ouabain, are plant-derived compounds that affect the heart by inhibiting the Na+/K+ ATPase pump, increasing intracellular calcium levels, and improving myocardial contractility.

(b) Gene Therapy:

Gene therapy involves the introduction, removal, or alteration of genetic material within a person’s cells to treat or prevent disease. It is used in the treatment of genetic disorders, cancers, and certain viral infections.

8. Write the structural elucidation of (8+7)

(i) Citral:

  • Structure: Citral is an aldehyde with a C10H16 formula. It is a mixture of neral and geranial, isomers of citral.
  • Spectral Data:
    • IR: Aldehyde C=O stretch at 1725 cm-1, C-H stretch at 2920 cm-1.
    • 1H-NMR: Signals for aldehyde proton at 9.6 ppm, methyl protons at 1.7-1.9 ppm.
    • Mass Spectrum: M+ at 152 m/z.

(ii) Penicillin G:

  • Structure: Penicillin G is a β-lactam antibiotic with a thiazolidine ring, a β-lactam ring, and a side chain.
  • Spectral Data:
    • IR: Amide C=O stretch around 1700 cm-1, NH stretch at 3200 cm-1.
    • 1H-NMR: Signals around 3.8-4.2 ppm for methylene protons, aromatic protons at 6.5-7.2 ppm.
    • Mass Spectrum: M+ at 334 m/z.