Table Of ContentACADEMIC PRESS RAPID MANUSCRIPT REPRODUCTION
Art in Biosynthesis
The Synthetic Chemist's Challenge
Volume I
Darshan Ranganathan Subrannania Ranganathan
Department of Chemistry
Indian Institute of Technology Kanpur
Foreword by
D.H.R. Barton
Imperial College, London
ACADEMIC PRESS New York San Francisco London 1976
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1976, BY ACADEMIC PRESS, INC.
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Library of Congress Cataloging in Publication Data
Ranganathan, Darshan.
Art in biosynthesis.
Bibliography: p.
Includes indexes.
1. Biosynthesis. 2. Chemistry, Organic.
I. Ranganathan, Subramania, joint author. II. Title.
QH345.R36 574.l'929 76-4108
ISBN 0-12-580001-0
PRINTED IN THE UNITED STATES OF AMERICA
This Work Is Dedicated to the Cause of
A Greater Awareness of
Nature by Man,
with Fond Hopes for a Deeper Appreciation
of Her Presence in Our Midst and an Increased
Desire to Simulate Her Experience in Building
Molecular Frameworks
Preface
Art in Biosynthesis projects Nature as an organic chemist supreme, and presents representative
examples whose biosynthetic pathways are known on the basis of experimentation. Art in Bio-
synthesis, like the earlier Art in Organic Synthesis pays tribute to the creativity associated with the
construction of molecular frameworks. The style of presentation of this book is similar to that of
Art in Organic Synthesis to enable a quick comparison of the specific synthetic strategies. Such a
comparison cannot but profoundly influence us and lead the art of organic synthesis in a direction
dictated by Nature, which would indeed be most desirable. Simple in her means but inexhaustively
rich in imagination and application, Nature operates more deftly whereas man's conquests with his
vast armory of reagents and an infinite choice of reaction conditions, although awe inspiring and
vastly impressive, cannot create that gentle glow of utter fascination. There is no need for us to
regret our inadequacies. Nature has been building carbon frameworks for the past five billion years,
and has been producing the necessarily highly sophisticated assemblies incorporating the genetic
apparatus for nearly three billion years. Comparatively, man's experience as a creator of molecular
frameworks is nascent and herein lies our relative lack of versatility and astuteness in planning. For
example, Nature produces nearly 1000 indole alkaloids with just two building blocks, namely,
tryptophan and loganin! The chemical simulation of biological processes is an endeavor that has
captured the imagination of the organic chemists in recent times. This book is intended to promote
this highly desirable transition. The largely pictorial presentations are followed by, in addition to
the author index and subject index, a glossary, and α-amino acid index, a reagent index and
reaction-type index to enable ready retrieval of information. In a large number of cases, biological
reaction mechanisms are interpreted on the basis of in vitro experience. These are provided by us to
maintain continuity and to emphasize the fact that biological transformations strictly follow the
laws of bond-forming and bond-breaking that have been deduced from experience with in vitro
systems.
We would like to express our deep sense of gratitude to Sir Derek Barton for his encouragement
and patronage, which has, time and again—buffeted as we are with the ever present perturbations-
helped us to align ourselves firmly to academic goals. We express our sincere indebtedness to
Professor M.V. George of our department for his ever available encouragement, patronage, indul-
gence, and understanding.
It is with great pleasure that we acknowledge our gratitude and indebtedness to Mr. Nihal Ahmad
IX
PREFACE
and Mr. D.S. Panesar who are entirely responsible for the production of this manuscript. These
colleagues took as much pride in the book as ourselves and their exemplary dedication to the
arduous task was to us a great encouragement. We thank Mr. V.A. Narayan for his meticulous
compilation of the author index.
We are most grateful to Academic Press, for their interest in the work, which was mainly responsi-
ble for the rapid progress of the book.
Darshan Ranganathan
Subramania Ranganathan
x
Foreword
Organic chemists have always been interested in the biosynthesis of natural products. At first, the
main purpose of biosynthetic theory was to aid in the deduction of structure. At a time when
structural determination was very difficult, the aid of a biosynthetic hypothesis could be invaluable.
Robinson's derivation of the structure of morphine is a pertinent example.
Much, however, has changed in organic chemistry in the last 30 years. First, thanks to physical
techniques, especially X-ray crystallography, the determination of structure has become a trivial
matter. Second, thanks to radioactive labeling, it is now possible to confirm, or to disprove, a
biosynthetic hypothesis. Indeed, in favorable cases, every sequential step in a long biosynthetic
sequence can be elucidated. Of course, not all cases are favorable, because of difficulties of transfer
of metabolites through cell walls. However, much has been accomplished, especially with plants and
with microorganisms.
Once a biosynthetic sequence has been determined, it can be compared with biosynthetic
hypothesis. It is indeed gratifying when the two are in agreement and when hypothesis can be used
to make yet further, verifiable, predictions.
An established biosynthetic sequence is a challenge to the synthetic organic chemist to imitate
and to equal Nature. Imitation is, in many cases possible, but we are far from equaling Nature in
the yield and stereospecificity of her processes.
Art in Biosynthesis is a work of appreciation and criticism of the beauty of biosynthetic processes
and of the interaction between man (the organic chemist) and Nature. It contains numerous well-
chosen examples and will be of value as a source book, as an inspiration to research, and even more
perhaps, as an aesthetic work of appreciation. The two authors are, by ability and background,
specially gifted to write such a book. I am sure that this work will be very well received by chemists
and biochemists.
Sir Derek Barton, D.Sc., FRS,
No bei Laureate
Hof mann Professor of Organic Chemistry
imperial College of Science and Technology
London
xi
AJMALICINE
Π ΓΤ
H*
The synthesis of AJmalicine from vincoside is an excellent
illustration of Nature's subtle art of changing carbon frame-
works by fewj entirely rational transformations.
-\ hydrolysis 1-
OGIu
Me0 C
2
Vincoside(see p.178)
hemiketal
opening
1
AJMALICINE
Michael addition!
-Γ cyclisation J ^
[reduction J
A. R. Battersby, Pure and Appl. Chem., 14, 117 (1967)5
A. R. Battersby, R. S. Kapil, J· A. Martin and L. Mo;
Chem. Comm., 133 (1968); P. Loew and D. Arigoni, Chem.Comm.,,
I37 (I968); A. R. Battersby, A. R. Burnett and P.G. Parsons,
Chem. Comm., I28O (1968); A. I. Scott, Ace. Chem. Res., 3_
151 (1970); A. I. Scott, Bioorg. Chem., _3, 398 (197^).
2
AMMONIA NH
3
The biosynthesis of ammonia - nitrogen fixation - is next
3
to photosynthesis the most important operation that is associa-
3
ted with life. Nearly all the nitrogen needed for growth is
provided from biosynthesis with chemical fertilisers playing a
minor role. The transformation of nitrogen to ammonia is a
difficult process and jm vitro is accomplished by hydrogénation
at high temperatures and pressures. Yet^ in Nature the same
net reaction is achieved under ambient conditions! It was only
in the last decade after an intensive effort the salient
y 5
aspects of Nature's fascinating fnitrogen-fixing! system became
understood leading to intense current efforts to simulate the
p
biological nitrogen fixation.
Mo containing /
M o - N = N —[ AT P }-
Enzyme (Mo - E)
II ΙΠ
1. 6 Fe 6 Fe
Mo— N = N (ferredoxin)
L 16H4
Activated Nitrogen
complex
Mo-E ♦ 2NH
3
3
