PHARMACEUTICAL ANALYTICAL TECHNIQUES

a) UV-Visible Spectroscopy: Basic principles, interaction of electromagnetic radiation with matter and its effects (electronic transitions). Concept of chromophore and auxochrome, effect of conjugation, solvent and pH. Instrumentation (components and their significance). Absorption spectra of organic compounds and complexes illustrating the phenomenon and its utilization in qualitative and quantitative studies of drugs including multicomponent analysis. Woodward-Fieser rules for caculating absortion maximum for unsaturated hydrocarbons. Difference and derivative spectra.

b) Infra-Red Spectroscopy: Interaction of infrared radiation with organic molecules and it’s effects on bonds. Instrumentation- Dispersive IR spectrophotometers and Fourier transform spectrophotometers. Sample handling for IR spectroscopy. Interpretation of IR spectra.  Brief note on ATR. (Attenuated Total Reflectance).

Nuclear Magnetic Resonance Spectroscopy: Fundamental principles of NMR,  instrumentation (components and their significance). Chemical shifts concept, spin- spin coupling, spin-spin decoupling, shielding and deshielding, solvents. signal multiplicity phenomena in high resolution PMR. Interpretation of PMR spectra.

Brief introduction about Carbon-13 NMR and 2D NMR Spectroscopy.

Mass Spectrometry: Basic principles and instrumentation (components and their significance). Ionization techniques, mass spectrum and its characteristics, molecular ion, metastable ions, fragment ions; fragmentation processes, fragmentation patterns and fragment characteristics in relation to parent structure and functional groups. Relative abundances of isotopes and their contribution to characteristic peaks. 

Chromatographic Techniques: Classification of chromatographic methods based on mechanism of separation and their basic principles. Gas chromatography: Instrumentation, column efficiency parameters, derivatisation methods, applications in pharmaceutical analysis. Liquid chromatography: Comparison of GC and HPLC, instrumentation in HPLC, normal and reversed phase packing materials, column selection, mobile phase selection, efficiency parameters, applications in pharmaceutical analysis. Instrumentation and applications of HPTLC, ion exchange chromatography, gel permeation chromatography, chiral chromatography, flash chromatography, and supercritical fluid chromatography (SFC).

a) Electrophoresis: Principles, instrumentation and applications of moving boundary electrophoresis, zone electrophoresis (ZE), isotachphoresis, isoelectric focusing (IEF), continous electrophoresis (preparative) and capillary electrophoresis. SDS gel electrophoresis and blotting techniques.

b) Radio immunoassay and ELISA: Principle, instrumentation, applications and limitations.

ADVANCED PHARMACEUTICAL ORGANIC CHEMISTRY – I

Stereochemistry: Elements of symmetry-plane of symmetry, center of symmetry, alternating axis of symmetry and simple axis of symmetry. Nomenclature – D, L and R, S- nomenclature, sequence rules, kinds of molecules displaying optical activity. Stereochemistry of biphenyls, allenes and spiranes. Cis/Trans, E-Z isomerism resulting from double bonds, monocyclic compounds, fused ring systems. Racemic modifications and methods of resolution of racemic mixtures. Asymmetric Synthesis and stereoselective synthesis.

Reactive Intermediates: Definition, generation, stability, structure and reactivity of free radicals, carbocations, carbanions, carbenes, nitrenes/ nitrenium ions.

Mechanisms of Organic Reactions: Electrophilic (addition and substitution), Nucleophilic (addition and substitution), elimination and free radical (addition and substitution) reactions.

Pericyclic Reactions: Electrocyclic, cycloaddition and sigmatropic reactions-introduction, terminology and mechanism with suitable examples.

Molecular Rearrangements: 

            1. Carbon to carbon migration: Wagner- Meerwin rearrangement, Claisen rearrangement, Pinacol-pinacolone rearrangement and Benzil- benzilic acid rearrangement. 

            2. Carbon to nitrogen migration: Hoffmann rearrangement, Curtius rearrangement, Beckmann rearrangement and Lossen rearrangement. 

            3. Carbon to oxygen migration: Bayer- Villager rearrangement and rearrangement of hydroperoxides.

ADVANCED MEDICINAL CHEMISTRY – I

Theoretical aspects of drug action: Introduction, brief account on various forces involved in drug-receptor complex, types of receptors. Theories of drug-receptor interactions: 1) occupancy theory, 2) rate theory, 3) induced fit theory, 4) macro molecular perturbation theory, 5) topographical and stereo chemical considerations, 6) Ion channel blockers. Case history of drug development – cimetidine.

Design and application of prodrugs: Prodrug concept, choice and function of pro-moiety, bioreversible derivatives for various functional groups, applications of the pro-drug approach.

Targets for the development of following chemotherapeutic agents: antiulcer, analgesic, anti-inflammatory, antifungal, antiangiogenesis and antihypertensive agents.

  

Biotransformation of drugs: Enzymes responsible for biotransformation, microsomal and non-microsomal mechanisms. Phase-I and phase-II transformations with suitable examples. Factors influencing enzyme induction and inhibition.

Genesis of new drugs: Serendipity, random screening, extraction of active principles from natural sources, molecular modification of known drugs, selection or synthesis of soft and hard drugs, and rational drug design.

ADVANCED CHEMISTRY OF NATURAL PRODUCTS

Natural products as leads for new drugs: Introduction/history, approaches to discovery and development of natural products as potential new drugs selection and optimization of lead compounds for further development with suitable examples from antibiotics, CNS, and cardiovascular agents.

Alkaloids: Introduction and general methods of structure elucidation. 

From opium: morphine-structural elucidation, development of morphine analogues and morphine antagonists.

From Rauwolfia: Reserpine-structural eludication, structural modifications and uses.

From vinca rosea: vincristine and vinblastine - structural modification, semi synthetic derivatives, and uses.

Steroids: Introduction, nomenclature, stereochemistry of steroids. Source and structure elucidation of cholesterol and diosgenin.

Structures, structural modifications and therapeutic uses of steroidal anti-inflammatory agents and antifertility agents.

Polypeptides and proteins: introduction and general methods of separation, general methods of degradation and end group analysis, general methods of synthesis of peptides. Primary, secondary, tertiary and quaternary structure of proteins; chemistry of insulin.

Miscellaneous compounds: Structure, structural modifications, mechanism of action and therapeutic uses of a) taxanes b) camptothecin c) artemisicin e) ginkolides and f) gymnemic acids.

ADVANCED PHARMACEUTICAL ORGANIC CHEMISTRY – II

Synthetic Reagents and Applications: Lead tetra acetate (LTA), n-bromo succinamide (NBS), osmonium tetraoxide, lithium aluminium hydride (LAH), sodium borohydride, DCC (Dicyclohexyl carbodimide), and 2,3-dichlro-5,6-dicyano-1,4-benzoquinone (DDQ).

Mechanism and applications of reactions and reagents:

            a. Claisen ester condensation, 

            b. Mannich reaction, 

            c. Micheal addition, 

            d. Witting reaction, 

            e. Synthetic applications of ethyl aceto acetate, diethyl malonate, ethylcyano acetate.

Development & scale up of process for the manufacture of new pharmaceuticals: 

            1. Introduction, synthetic route selection, development and scale up, optimization of synthetic routes-yield improvement, investigative approach, streamlining the process.

            2. A brief account on Green Chemistry: principles, and applications.

  

Synthetic Strategies: Introduction to disconnection approach, consecutive vs convergent synthesis, various strategic approaches in retro synthesis, strategic bond approach-preliminary scan, criteria in disconnection of strategic bonds, identifying strategic bonds in rings.

Combinatorial Chemistry: Introduction, solid phase techniques, parallel synthesis, mixed combinatorial chemistry, deconvulution techniques, tagging, photolithography, limitations of combinatorial chemistry, planning and designing of combinatorial synthesis.