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
specific areas 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 condenser mechanical 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 project type 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 : 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 totaling 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 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’.
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