Chemistry and creativity: Advanced Practical Medicinal Chemistry
Advanced Practical Medicinal Chemistry
The ‘art and skill’ for the preparation of ‘newer drug molecules’ is a pivotal creative and an
exceptionally great intellectual exercise that essentially serves as a fulcrum to plethora of specificareas of scientific research, ranging from the most applied to the most academic. Accordingly,
the medicinal chemist, organic chemist, biologist, pharmacologist, biochemist,
biotechnologist, phytochemist, genetic engineer, materials scientist, and polymer scientist, in
an university or an industry, all must have genuinely encountered with the most challenging
and intricate task of performing a reaction ultimately leading to an entirely new organic preparation
exhibiting certain specific actions on the biological system to combat diseases in the
ailing human beings.
Invariably, the wonderful ‘magic’ of modern organic synthesis, based on host of documented
theories, hypothesis, organic name reactions (ONRs) amalgamated with logistic, scientific
and assertive reaction mechanism(s), in fact, genuinely paved the way of complicated, notso-
easy, cumbersome course of reactions much simpler and understandable.
The advent of ever-more sophisticated and many supportive modern analytical techniques,
such as : UV, IR, NMR, MS, ORD, CD, AAS, FES, GC, HPLC and the hyphenated
techniques as well, have tremendously enhanced the confidence of medicinal chemists to such a
magnitude as to maximize both the chances of success rate and probability factor.
Besides, the use of organic and inorganic chemicals employed as reactants, catalysts,
medium of reaction, purifying substances etc., are not only harmful but also hazardous in nature.
Nevertheless, the various conditionalities of critical and specific reactions are sometimes
articulated and spelled out so meticulously that one has to follow them just like ‘gospel truth’,
to accomplish the right synthesis, and hence, the right product.
It is, however, pertinent to mention here that the UG and PG students, associated with
the myth and reality of ‘drug synthesis’ should make an honest attempt to carry out a particular
synthesis of a drug substance with a most tried and tested methodical, scientific and rational
approach, so that one may get reproducible results under a particular reaction in a seamless
manner.
The copious volumes of textbooks, scientific research journals, monographs, review articles
on related topics like : organic chemistry of drug synthesis, chiral chemistry, drug design,
principles of medicinal chemistry, organic medicinal and pharmaceutical chemistry, and medicinal
chemistry provide ample evidence and scope to suggest that the comprehensive in-depth
knowledge together with utmost specialized state-of-the-art know-how of the various techniques
is an absolute necessity and basic requirement to have a real understanding with regard to the
practical aspects of ‘Medicinal Chemistry’.
In ‘Advanced Practical Medicinal Chemistry’, an attempt has been made to stress
the much needed requirement of both undergraduate and graduate students specializing in the
field of Pharmaceutical Chemistry to learn how to synthesize ‘drugs’ in the laboratory. Unfortunately,
the common available textbooks ordinarily referred to by the Pharmacy Students
mostly deal with the synthesis of pure ‘organic compounds’ ; and hence, do not provide the
real and much needed subject matter relevant to a budding ‘Medicinal Chemist’.
The ‘Advanced Practical Medicinal Chemistry’ comprises of four major chapters
that are intimately associated with specific emphasis on the synthesis of a broad range of some
typical and selected ‘drugs’ commonly found in the therapeutic armamentarium.
Chapter-1 deals with ‘Safety in a Chemical Laboratory‘. It consists of various aspects,
namely : guard against personal safety ; conduct in a chemistry laboratory ; neatness and cleanliness
; after-hours working ; guidelines for accident or injury ; storage of chemicals/reagents in
a chemical laboratory ; glass ware ; waste disposal ; an ideal chemistry laboratory ; and toxicity
and hazards of chemicals/reagents.
Chapter-2 consists of ‘Drug Synthesis’. First, aspect being—‘Conceptualization of a Synthesis‘
viz., prime considerations in designing synthesis ; the Synthon Approach ; reaction
specificity. Secondly, Reaction Variants, viz., structural variants ; interchangeability of functional
moiety ; selectivity in reactions ; protection of functional moieties ; elimination of functional
moieties ; annealation reactions ; fragmentation reactions. Thirdly, Stereochemistry, viz.,
nucleophilic substitutions (SN2), ionic additions to C-C double bonds ; catalytic hydrogenation ;
acid or base promoted enolization of compounds, reductions of cyclohexane ; and cycloadditions.
Chapter-3 comprises of ‘Performing the Reactions’. The wide range of latest laboratory
techniques invariably employed in a reasonably well equipped chemical research laboratory or
a chemical laboratory for actually performing the specifically desired reactions and other equally
important operational measures have been dealt with in an explicit and lucid manner. The
various aspects included in this chapter are, namely : solvent stills (with continuous still collecting
head)-reactions performed at elevated temperatures-large scale reaction and slow addition
of reagents-low temperature reactions-reaction above room temperature using a condensermechanical
stirrer-mechanical shaker-crystallization at low temperature-distillation under reduced
pressure-small scale distillation-performing the reaction, and -photolysis.
Chapter-4 i.e., the last chapter, has been exclusively devoted to—‘Synthesis of Medicinal
Compounds’ which vary in length from the single-stage reaction to the multi-stage or projecttype
synthesis. In fact, it is the backbone of the present textbook and specially designed to
inculcate the sense of creativity, learning the art of synthesis, and above all inject the spirit of
zeal and enthusiasm amongst the ‘medicinal chemists’ to tackle most synthesis-related problems
with great ease, confidence and fervour. It embraces ‘three’ specific areas of interest
confined to the ‘synthesis of drugs’, such as :
(a) Types of Chemical Reactions e.g., acetylation methods-benzoylation methodssulphonation
methods-bromination methods-condensation reactions ; and diazotization and
coupling reactions ;
(b) Organic Name Reactions (ONRs) e.g., Bart reaction-Diel’s-Alder reaction-Friedel-
Craft’s reaction-Fries reaction-Grignard reaction-Hoesch reaction-Perkin reaction-Mannich
reaction-Michael reaction, and Reimer-Tieman reaction ;
(c) Selected Medicinal Compounds : It includes the synthesis of forty selected medicinal
compounds having a wide variety of therapeutic action(s).
An intensive and extensive care has been exercised painstakingly and meticulously to
discuss in details each and every medicinal compound under the above mentioned three categories
i.e., (a) through (c) in a particular original style of presentation that essentially includes :
( viii )
chemical structure-synonym(s)/chemical name(s)-theory-chemicals required-procedure-precautions-
recrystallization-theoretical yield/practical yield-physical parameters-uses, and -questions
for viva-voce.
A subtle, but no less profound effect of this completely new approach as given in the
‘Advanced Practical Medicinal Chemistry’ comprising of syntheses totalling eighty selected
‘drug substances’ would not only benefit the undergraduate and graduate students in
Pharmaceutical Chemistry in Indian Universities and other developing countries as well, but
also go a along way to help the esteemed teachers involved in the handling of such courses who
always genuinely felt the dire necessity of such a compilation for the ‘academics’ in particular.
The ‘medicinal chemists’ involved in ‘Bulk Drug Manufacturing Operations’ may also
find this presentation as a handy reference book in the domain of their ever expanding and
demanding profession.
In case, the above outlined objectives have been duly achieved, actual users of this textbook
must be able to accomplish their synthetic problems with greater ease and confidence.
Synthesis of ‘Medicinal Compounds’ is not only satisfying but also exciting, and provides an
ample opportunity to explore an individual’s inherent talent and enormous strength of ‘real
creativities’
Ashutosh Kar
Advanced Practical Medicinal Chemistry
