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Book Review The Inositol Phosphates. Chemical Synthesis and Biological Significance. By D. C. Billington

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himself by means of two scholarships, was influenced by
R. P. (Ronnie) Bell and Sir Robert Robinson, and received
his B. A. (1940), D. Phil. (1942), and M. A. (1943). In addition to discussing his research on alkaloids (yohimbine) and
his wartime work on explosives, sulfa drugs, antimalarials,
and penicillin (the last two as a postdoctoral fellow with Sir
Robert Robinson at Oxford’s Dyson Perrins Laboratory), he
relates “the most important event of my life,” his meeting
with “someone who was more than my equal,” Mary
Williamson, whom he wed on June 3,1944, three days before
D-Day. Because Mary was a historian, scholar, and author
rather than a scientist, their relationship has been a mutually
beneficial one (“we tend to look at things from different
viewpoints”). Their almost half-century marriage has been a
very close and happy one, resulting in two sons, Robert and
Steuart. both of whom now work with computers.
From 1945 to 1951 Dewar was a “physical chemist” at the
new laboratory set up by Courtaulds, Ltd. (the rayon and
acetate fibers manufacturer) at Maidenhead near London,
where he carried out basic research on polymerization and
other problems, while teaching himself physical chemistry
and writing his first book, The Electronic Theory of Organic
Chemixrr.~,(1949), “the first general account of organic
chemistry in terms of M O theory.” Although a move from
an industrial position to an academic position is unusual
(another exception to the rule was Carl Djerassi’s move from
Syntex to Wayne State University, related in Steroids Made
It Possible, an earlier volume in the ProfiZes series), in 1951
Dewar was offered the position of Professor of Chemistry
and Department Head at Queen Mary College, University of
London, the youngest person (age 33) to be appointed to a
chair in London except for one or two mathematicians. At
QMC, where Mary belatedly obtained her Ph.D., Dewar
carried out research on resonance theory, bond localization,
molecular orbital (PMO) theory, structures of phosphonitrile chlorides, condensation of steam on metal surfaces, liquid crystals, and NMR, ESR, and NQR spectroscopy.
In 1959 Dewdr was appointed to the late Morris S. Kharasch’s chair at the University of Chicago, the first full professor to defect in the “brain drain”. Here he continued
his work on borazaromatic compounds and “one-off‘’
projects- -relatively short-term projects designed to answer a
specific question and providing ideal training for graduate
students. He also began his current theoretical program described at the beginning of this review, which he developed
fully during his tenure as Robert A. Welch Professor of
Chemistry at the University of Texas at Austin (1963-1990).
In the course of his account he discusses with praise or sometimes with scorn the contributions of others, and the book
reads like a “Who’s Who” of organic chemistry. He champions the contributions of chemists such as Christopher
Longuet-Higgins and M. G. Evans, whose work he thinks
has not been sufficiently appreciated.
This picture of Dewar that emerges from these pages is one
of a complex, brilliant, no-nonsense scientist and devoted
husband and father. Insight into his character is best conveyed in his own words. Being scrupulously realistic in evaluating his own abilities and shortcomings and those of others, he expresses himself with a refreshing frankness and
matter-of-fact candor that sometimes appears brash or controversial: “Because I have . . . never been a respecter of
persons, let alone of ‘experts’, my contributions have . . . not
always been expressed too tactfully” (p. 183). Being secure
and comfortable with who he is, he can make statements that
might be considered boastful if uttered by others: “My arrival in Texas put the place on the academic map” (p. 122).
“I probably know more about [ the mechanism of pericyclic
A I I , ~ < wChcm
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EN‘. EnxI. 1993. 32. N o . 7
reactions] than any other chemist who is still active” (p. 139).
At other times his characteristic forthrightness results in
statements that might be misconstrued as false modesty: “I
have come up with a number of similar contributions that
have given me an undeserved reputation for original thinking. I am not, in fact, original in the proper sense of the term.
I am, however, good at solving problems.. .” (pp. 39-40). “I
am hopeless at administration. I am good at seeing what has
to be done but hopeless at getting it done. A good administrator operates by manipulating people. I have never been
any good at this” (p. 67). “I have always been very bad at
publicizing the things I have done” (p. 91). Unlike too many
of us, he benefits from his experiences. In his concluding
chapter, titled “Debts Owed, Lessons Learned,” he decries
the growing trend for conformity and the tendency for
chemists to take their work too seriously, and he criticizes
the policies of the National Science Foundation and the
Journal of the American Chemical Society. Although he voices his opinions strongly, he is not opinionated: “I have always been ready, as the record shows, to abandon any chemical belief in the face of valid arguments or new evidence”
(p. 184).
We warmly recommend this eminently readable and very
human autobiography of Professor Dewar, graced by
46 photographs from his family albums, to organic chemists,
undergraduate and graduate chemistry students, historians
of chemistry, and anyone interested in the development of
chemistry, the conduct of research, and the personal and
professional lives of scientists.
George B. Kauffman, Laurie M . Kauffinan
California State University
Fresno, CA (USA)
The Tnositol Phosphates. Chemical Synthesis and Biological
Significance. By D.C. Billington. VCH Verlagsgesellschaft, Weinheim/VCH Publishers, New York, 1993. XIV,
153 pp., hardcover D M 126.00-ISBN 3-527-28152-5/089573-977-1
It is now almost a decade since Michael Berridge and his
collaborators reported in Nature: “. . . . micromolar concentrations of Ins(1 ,4,5)P3 (~D-~)JO-inOSitOl
1,4,5-trisphosphate) release Ca2+ from a non-mitochondria1 intracellular
store in pancreatic acinar cells. Our results strongly suggest
that this is the same store that is released by acetylcholine.”
Thus, some 30 years after the beginnings of this field with the
observation by Lowell Hokin of agonist-stimulated phospholipid turnover (the so-called “phospholipid effect”) and
8 years after the correlation made by Michell in 1975 with
agonist-stimulated intracellular Ca2 release, the final missing molecular link was found in 1983 in the form of a second
messenger, the polyphosphorylated cyclitol Ins( 1,4,5)P3.
Since 1983 progress in this new area of signal transduction
has been nothing short of breathtaking. Indeed, Lowell
Hokin recently remarked : “The phosphoinositide field is
currently the number one field in biochemistry in the number
of citations (excluding molecular biology).” Small wonder,
then, that most workers in the field, be they chemists or
biologists, find it almost impossible to keep fully abreast of
events. Thus one tends to rely upon the all-too-frequent biological reviews to escape the need to digest the voluminous
primary literature. Such reviews, however, rarely address
chemical matters in any depth, if at all, and it is therefore a
pleasure to see at last this new book, where the author has
clearly made an effort to focus upon a very particular need,
that of the biological and medicinal chemist.
:(? VCH Veriugsgeseiischufl mhH, D-69451 Weinherm, 1993
+
OS70-0833/93/0707-1/033 10.0(1+ .2Sj0
1103
With the opening of this new chapter in cellular signalling
it was soon clear that there was a prime need for synthetic
chemical involvement, and there has been a very significant
revival of interest in the chemistry of inositols since the mid1980s, beginning with the first synthesis of Ins(l,4,5)P3 in
1986. While progress here has also been relatively rapid, and
necessarily highly competitive, the chemistry of the new inositol phosphates is still a small enough field to be concisely
reviewed. Until now, however, there have only been two
comprehensive major chemical reviews in this area, and one,
indeed, by the author of this present book. While “The Inositol Phosphates” clearly represents a useful addition to this
literature, I admit to being more than a little apprehensive
about how much further this book could go in relation to
these existing reviews.
The chemical synthesis of inositol polyphosphates presented a number of problems, namely: the regiospecific protection of inositol in order to afford suitable intermediates
for phosphorylation; the optical resolution of such intermediates; the polyphosphorylation of intermediates possessing
vicinal diol functionalities, where it is essential to avoid the
facile formation of 5-membered cyclic phosphates; deblocking of fully protected polyphosphates, without concomitant
migration of phosphate groups; and finally, purification of
the final water-soluble polyphosphate. Essentially, these
problems have all been overcome and it is now, at least in
principle, possible to synthesize any inositol polyphosphate.
This message is well conveyed by the book. Much effort,
however, is still being expended in the development of novel
routes to optically active inositol phosphates and improvement upon the established methods developed to combat the
above problems. All this information, and more, with clear
summaries of a large number of synthetic strategies, is provided excellently in this book. Although clearly aimed at
chemists, it would perhaps also be useful to biologists who
want a concise survey of chemical progress and, as many do,
a basic grounding in the more structural, and particularly
stereochemical, aspects of this field. In view of this, the biological background here, while adequate for a chemical audience, forms only a minor part of the book and the author,
wisely, does not attempt to become embroiled in any of the
many controversies currently raging in this expansive field.
After equipping the reader in the earlier chapters with
enough background biology to understand the rationale behind the synthetic work, the author launches into Chapter 3
which discusses in depth the basic problems of inositol
polyphosphate synthesis, namely the protection, phosphorylation, deprotection, and resolution steps mentioned above.
A systematic treatment of mono-, bis-, tris-, and tetrakisphosphates then follows, with detailed accounts of various
approaches, covering most of the chemical literature up to
1991. A most welcome Chapter 8 describes some of the efforts expended in the synthesis of inositol phosphate analogues, now a major theme in organic chemistry, with the
prospect of developing enzyme inhibitors, receptor antagonists, and perhaps even therapeutic agents of the future.
The final chapter provides an insight into some of the
more recent synthetic activity, including some 1992 publications. Nevertheless, I regretted that the book as a whole
could not be more up-to-date, presumably due to the production time-scale. As always in such a field, review articles
and books run the risk of rapidly becoming out of date, and
sadly this has been all too true for biological articles and
books on the polyphosphoinositide pathway. However,
since the volume of chemical work is clearly smaller than
that in biology, and the synthetic chemistry reported here is
well established and not the subject of anywhere near as
1104
0 VCH
Verlagsgesellschajt mbH, 0-69451 Weinheim. 1993
much controversy, this may be less important in this case. I
felt that the book ended rather abruptly, and I would have
liked to see space given to a concise summary of chemical
progress to date and, more especially, to speculation, philosophical and otherwise, on future chemical directions in this
research area.
Despite these shortcomings, I can recommend “The Inositol Phosphates” to anyone who requires a comprehensive
summary of some seven years of chemical research in this
rapidly expanding field. It will provide an invaluable compendium for anyone contemplating synthetic work in this
area. This book deserves a place upon the bookshelf of any
active inositol phosphate or carbohydrate chemist, and it
will hopefully give encouragement and heart to those
chemists who have been too afraid of the fast-moving nature
of this field to join in the game.
B. V. L. Potter
Department of Medicinal Chemistry
School of Pharmacy & Pharmacology
University of Bath (UK)
Fundamentals of Crystallography. (Series: IUC Texts on
Crystallography, Vol. 2.) Edited by C.Giucovazzo. International Union of Crystallography, Oxford University
Press, Oxford, 1992. XI, 654 pp., paperback f 27.50.ISBN 0-19-855 578-4
Although chemical crystallography has undergone rapid
developments and become more widely used during the last
few decades, one could hardly claim that this has been accompanied by a corresponding surge in the publication of
up-to-date monographs and textbooks on the subject. As in
most cases, exceptions prove the rule; in particular the International Union of Crystallography has recently published a
number of excellent books that go some way towards remedying this. The volume reviewed here also belongs to this
category; under the editorship of C. Giacovazzo it deals with
important aspects of modern crystallography, mainly chemical. All the authors areeminent representatives of the Italian
school of crystallography, as also is the editor who has contributed three of the chapters.
What detailed aspects are covered? Appropriately one
should first mention the three chapters by C. Giacovazzo:
“Symmetry in Crystals”, “Crystallographic Computing”,
and “The Diffraction of X-Rays by Crystals”. These are
followed by “Experimental Methods in X-Ray Crystallography” (H. L. Monaco), “Solution and Refinement of Crystal
Structures” (D. Viterbo), “Ionic Crystals” (F. Scordari),
“Molecules and Molecular Crystals” (G. Gilli), and “Protein
Crystallography” (G. Zanotti). The book ends with a treatment of “Physical Properties of Crystals” by M. Catti. The
last four chapters introduce aspects of crystal structure science that go far beyond merely describing the tools used for
structure determination, and especially here one notes with
approval that the authors have avoided following well-trodden paths in their presentation of the material. The book also
excels by the exemplary way in which this has been done, and
by the unusually clear layout, which is in the style of the
textbooks by Atkins (lots of attractive illustrations and diagrams!). Furthermore, each chapter includes an account of
the latest developments, while always taking care to put
these into a practical context, which is a highly commendable
approach. Thus the book makes very worthwhile reading,
even for those with long experience in using the methods,
especially as there are plentiful references to recent relevant
0570-0833/93/0707-1104$ /0.00+ ,2510
Angew. Chem. In[. Ed. Engi. 1993, 32, No. 7
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