V. Andrushko – Stereoselective Synthesis of Drugs and Natural Products

Описание

The world around us is chiral, and chiral phenomena play
a significant role in nature. One phenomenon is
homochirality—a property of naturally occurring chiral
compounds that consist of only one enantiomer (in either
left- or right-handed form). All contemporary life-forms
involve unique molecular building blocks with threedimensional
(3D) stereochemistry such as amino acids,
sugars, active terpenes, and alkaloids. These naturally
occurring architectural masterpieces play a prominent role
in living systems constituting the basic units in biopolymers
and nanostructures. Enantiomerically pure monomeric
L-amino acids and D-carbohydrates, for example, construct
biopolymers (proteins, nucleic acids, or polysaccharides),
and they are linked together in such a way that all subunits
have the same chirality.
The biological activity of many pharmaceuticals, flavors
and fragrances, food additives, and agrochemicals is associated
with absolute configuration. Because two optical isomers
of the chiral compounds can exhibit different
biological activities and pharmacological profiles in living
systems, the development of stereoselective synthetic methods
and strategies for the generation of these precious entities
(from simple chiral target molecules to complex natural
products) in an efficient manner and with specific and more
varied 3D structures has become recently of great interest to
both the chemical and pharmaceutical industries. On the
other hand, systematic investigations of biological activities,
including pharmacology and toxicology, of individual
stereoisomers also has become recently commonplace for
all new chiral pharmaceuticals and other compounds with
potential bioactivity. Concomitantly, these trends have created
a rapid increase in the demand for stereoselective analysis
techniques that are capable of determining precisely
the stereoisomeric composition of chiral biologically active
compounds from syntheses, biological assays, or pharmacological
studies.
This book comprises 57 chapters. It is an attempt to
review the main preparative stereoselective methods for the
synthesis of chiral drugs and natural products as well as the
application of modern analytical methods and separation
techniques for analysis, isolation, and chiral separation
with emphasis on recent advances. After the general introductory
chapters covering general principles and methodologies,
nomenclature, general concepts, and strategies for
stereoselective synthesis, the chapters on individual stereoselective
synthetic methods are organized by the type of
bond formation.
This compilation embraces a wide variety of subjects,
such as solid-phase and microwave stereoselective synthesis;
asymmetric phase-transfer asymmetric catalysis and
application of chiral auxiliaries and microreactor technology;
stereoselective reduction and oxidation methods; stereoselective
additions; cyclizations; metatheses and different
types of rearrangements; asymmetric transition-metal–
catalyzed, organocatalyzed, and biocatalytic reactions;
methods for the formation of carbon–heteroatom and
heteroatom–heteroatom bonds like asymmetric hydroamination
and reductive amination, carboamination and alkylative
cyclization, cycloadditions with carbon–heteroatom bond
formation, and stereoselective halogenations; and methods
for the formation of carbon–sulfur and carbon–phosphorus
bonds, asymmetric sulfoxidation, and so on.
The different methodologies developed for the precise
determination of the stereoisomeric composition of chiral
compounds and chiral separation, such as gas and liquid
chromatography on chiral stationary phases, capillary electrophoresis,
and nuclear magnetic resonance (NMR) spectroscopy;
the methodologies for the determination of absolute configuration such as X-ray analysis, NMR, and
chiroptical methods; as well as the methodologies for the
resolution of racemates, e.g., crystallization, preparative
chromatography, and (dynamic) kinetic resolution
have attracted recently considerable attention. The state-ofthe-
art for these analytical methods and techniques are also
discussed in this book.
Stereoselective Synthesis of Drugs and Natural Products
is meant to serve as a reference book for scientists interested
in the chirality-related aspects of organic chemistry
and analysis, and it definitely will find a welcome audience
with researchers, lecturers, postdoctorates, and advanced
students of chemical and pharmaceutical departments, as
well as with researchers and R&D managers of chemical
and pharmaceutical companies working on the stereoselective
organic synthesis, asymmetric catalysis, biocatalysis
and organocatalysis, and stereoselective synthesis of drugs,
drug precursors, biologically active compounds and natural
products, medicinal and pharmaceutical chemistry, biochemical
and biomolecular science, drug discovery, drug
design and drug development, as well as chemical engineering
and biomedicine. With this book, every chemist working
on or interested in topics related to the stereoselective
synthesis of drugs and natural products will find in one
source gathered overviews they need and a full list of references
for further readings.
Although many good reviews and books are available
dealing with one or two of the above-mentioned methods,
reactions, or methodologies, they are provided in a different
scientific context and without experimental details. Usually,
their perspective is in accord with that of readers operating
in theoretical stereoselective synthesis or asymmetric
catalysis, but not with that of readers in experimental work
and application stereoselective methods for the synthesis of
biologically active and pharmacologically important chiral
compounds. This book is intended as a contribution to fill
this gap. Therefore, some typical experimental procedures
and general experimental details for some key-step
reactions of the total syntheses of biologically active compounds
have been provided.
Indeed, it was an extremely difficult task to summarize
and discuss in a single book limited by a certain number of
pages an almost endless number of existing examples and
stereoselective methods available in the scientific literature.
The enormous increasing activity of the researchers from
both academia and industry in the field of stereoselective
synthesis precludes a comprehensive treatment of even the
literature of the last 20–25 years. Therefore, nonefficient
methods with a low stereoselective outcome or pure yields
generally will be omitted.
Finally, we wish to thank all the authors, who graciously
accepted our invitations and contributed excellent
chapters to this book. Without them this book would
not have been possible. We would like to express our
gratitude to Jonathan T. Rose from Wiley for his
invaluable support in this project.