Book reviews

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Specialist Periodical Reports: Organophosphorus Chemistry, volume 32

D. W. Allen and J. Tebby, RSC, Cambridge, UK, 2002, x + 264 pp., price £210, ISBN 0-85404-334-9 Search PubMedThis volume of Organophosphorus Chemistry covers the literature from July 1999 to June 2000 and consists of six chapters covering the following topics: Phosphines and Phosphonium Salts by D. W. Allen (Chapter 1), Pentaco-ordinated and Hexaco-ordinated Compounds by C. D. Hall (Chapter 2), Tervalent Phosphorus Acid Derivatives by D. W. Allen (Chapter 3), Nucleotides and Nucleic Acids by M. Migaud (Chapter 4), Ylides and Related Species by N. Bricklebank (Chapter 5) and Phosphazenes by J. C. van de Grampel (Chapter 6).

Two topics which have not been covered this year despite featuring in previous volumes, are those on quinquivalent phosphorus acids and physical methods. In addition chapter 4 is limited to a discussion of mononucleotide chemistry only. On a more positive note, the chapter on tervalent phosphorus acid derivatives contains coverage of the material from the period July 1998 to June 1999, which was absent in volume 31. It is intended that the discussion of the omitted topics from this current volume will be done in volume 33 in a similar manner.

Despite these omissions, the volume still gives excellent coverage of many recent advances in organophosphorus chemistry. Notable areas include the synthesis of new chiral phosphines for application in metal-catalysed processes and the preparation of new penta- and hexaco-ordinated compounds, of particular interest being those containing sulfuryl stabilising groups. Advances in phosphorylation and chiral thiophosphorylation are featured in chapter 4, whilst chapter 5 covers the recent advances made in phosphorus ylide chemistry, including mechanistic and synthetic aspects. The final chapter on phosphazenes again gives excellent coverage of this difficult area, with the preparation of novel substituted ferrocenes using aza-Wittig and Staudinger reactions, being of particular interest.

Preparation of a volume of this nature is a challenging task and I can sympathise with the senior reporters who have obviously found it difficult to get contributing authors this year. The nature of organophosphorus chemistry is that it crosses many of the boundaries found within general chemistry and the preparation of specialist reports of this nature is one of the best ways to keep up to date with developments in your own field of interest and other closely related work.

Dr Patrick J. Murphy
University of Wales, Bangor, UK

Specialist Periodical Reports: Organophosphorus chemistry, volume 31

D. W. Allen and J. C. Tebby, RSC, Cambridge, UK, 2001, 336 + xiv pp., price £210, ISBN 0-85404-329-2 Search PubMedWhen Specialist Periodicals Reports started in the late 1960s I bought the first few volumes of Organophosphorus Chemistry for about five pounds each. After volume 6 they increased dramatically in price and I stopped buying them. Our library stopped taking them with volume 12 in 1981. I was astonished to be sent volume 31 (covering literature published from July 1998 to June 1999) as I had no idea they still continued. Many of the chapter headings are the same as 1969 including the quaint ‘quinquecovalent phosphorus compounds’. (Why? Surely you know, it's ‘correct’.) Most chapters concern the types of phosphorus compounds that people use in organic chemistry but there is a chapter on ‘Nucleotides and Nucleic Acids’ and another on ‘Phosphazenes’ that appeal to quite different audiences.

The selection of material is comprehensive and interesting. My own interests led me to read chapter 1, Phosphines and Phosphonium Salts (this contains phosphine oxides ‘and related chalcogenides’) and chapter 5, Ylides and Related Species (this contains ‘Structure and Reactivity of Lithiated Phosphine Oxide Anions’ – a belt and braces title as it is very difficult to lithiate an anion). I found several references in each chapter that were new to me and here lies the great advantage of books such as this. Nowadays searching for things on the web is very efficient. Sometimes too much so as we miss the randomness of loosely associated topics. In those two chapters I was led on from what I knew to some totally new things and this alone may give this series an increased value in the 21st century. No doubt even phosphazene chemists will find new things here. There are errors of course: on page 225 structure 27b is wrong, on page 232 in scheme 13 most of the AD mix is missing including even the Me group of methane sulfonamide, and on page 241 compound 122 is described as a phosphonate whereas it is a phosphine oxide. Nobody could compile a book of this sort without making errors and these are not misleading. There is an author index so you can do as I did and start by seeing if your best work appears. In my case it does – the same three references appear in chapters 1 and 5. The reviewers have done a great job for phosphorus chemists but the ridiculous price will prevent even libraries buying this book.

Stuart Warren
Cambridge University, Cambridge, UK

Chlorosulfonic acid – A versatile reagent

R. J. Cremlyn, RSC, Cambridge, UK, 2002, xiv + 308 pp., price £105, ISBN 0-85404-498-1 Search PubMedChlorosulfonic acid is undoubtedly an important industrial chemical with world production well over 300,000 tons per annum. In Chlorosulfonic acid a versatile reagent, the reader is presented with a very detailed review of all conceivable aspects of this reagent, ranging from its physical and chemical properties and preparation to a host of applications in synthesis, with in-depth discussion of reaction mechanisms.

After general chapters on the sulfonation and chlorosulfonation of organic compounds and the reactions of organic sulfonyl chlorides, there are chapters covering sulfonation and chlorosulfonation of specific aromatic compounds; of heterocyclic compounds and of aliphatic compounds; the reaction of chlorosulfonic acid with elements and inorganics; commercial uses; miscellaneous reactions and preparation, manufacture and properties of chlorosulfonic acid.

Chlorosulfonic acid still sees most general use in the sulfonation and chlorosulfonation of aromatic and heterocyclic systems. It is a highly reactive reagent and so the actual products formed are very substrate dependent. Chlorosulfonation can lead to sulfonic acids, sulfonyl chlorides or sulfones under the right conditions and stoichiometry. Side reactions such as chlorination can often occur, as well as rearrangement of alkyl and halogen substituents. The ‘versatility’ of chlorosulfonic acid does not really reflect the range of transformations it will effect, but rather the diversity of substrates it will react with. This is reflected in the two largest chapters in the book, which cover reactions of chlorosulfonic acid with aromatic systems and with heterocycles, and which are organised by ring system. This enables the reader to quickly find the likely products for a specific cyclic substrate.

The index also lists ring systems, as well as reagents and reaction types and information is straightforward to find.

The dedicated section on preparation, industrial manufacture and properties appears near the end of the book which seems odd chronologically – it might have been more intuitive to position it near the front. There was a certain amount of repetition, particularly in the short Miscellaneous reactions section which covered again much of the material from earlier chapters in an attempt to bring together reactions of a particular type, for example rearrangements and polymerisation.

Chlorosulfonic acid was first discovered back in 1854 and, perhaps not surprisingly, much chemistry referenced in the book was carried out in the 19^th and early 20^th centuries. There are already several reviews of this general area of chemistry pre-1990, although the book usefully summarises this information in one source. There is a brief (14 page) ‘recent references’ appendix in the book which contains a miscellany of synthetic applications, ranging from ink jet dyes, through asphalt to a Viagra synthesis. This covers the period 1999 to the year end 2001. In the main sections, it becomes clear that the majority of references post 1980 are to manufacturing process patents using chlorosulfonic acid, where a significant proportion of more recent developments lie.

University and industrial libraries are under increasing financial pressures and have to be more selective about what books and journals they buy. Much of the information in this book is available in part elsewhere, for example in Comprehensive Organic Chemistry, Comprehensive Heterocyclic Chemistry and Patai's Chemistry of Sulfonic Acids and Derivatives, not to mention a number of other reviews, some by Professor Cremlyn. Key industrial uses of chlorosulfonic acid are in the detergent, fine chemical and dye industries along with a number of other miscellaneous industrial applications. The book is likely to prove very useful as a reference text for process chemists in these areas.

Steve Smith
Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire, UK RG42 6EY

Handbook of Combinatorial Chemistry – Drugs, Catalysts, Materials

K. C. Nicolaou, R. Hanko and W. Hartwig, Wiley-VCH, UK, 2002, xxxi + 1114 pp. (2 volumes), price £225.00 (hardcover), ISBN 3-527-30509-2 Search PubMedThis book belongs to a number of monographs published recently that focus on the fast growing field of combinatorial chemistry. With over 1100 pages, it is the most comprehensive review of its kind published so far. The editors from the Scripps Institute in La Jolla, USA and the Bayer company, Germany, compiled contributions from 73 authors, more than three quarters of whom are from industry (mostly Bayer). Indisputably, this has an influence on the contents. The handbook is practice-oriented to a large extent – detailed descriptions of machinery used for multiple parallel syntheses or high-throughput analysis techniques are presented as well as aspects of the application of combinatorial methodology to process development. Yet, the majority of the 35 chapters deal with organic chemistry and its application to the construction of structurally diverse small molecules, still the major field of activity among all combinatorial disciplines. The book is structured in 5 sections: General Aspects, Synthetic Chemistry, Special Synthetic Topics, Molecular Design and Combinatorial Compound Libraries, and Novel Applications of Combinatorial Chemistry. Besides a short introductory part, the first section contains chapters on solid and soluble polymeric supports, encoding technologies, instrumentation and a large chapter on linkers for solid-phase synthesis. Consisting of 14 chapters, the synthetic part covers more than one third of the whole book. In detail, radical reactions, nucleophilic and electrophilic substitutions, eliminations, additions, oxidations, reductions, cycloadditions as well as reactions involving carbonyl groups, organometallic reagents and enolates are described. The last two chapters of this second section deal with palladium-catalyzed transformations and olefin metathesis. With few exceptions, the quality of the contributions in the first half of the book is excellent and an outstanding survey of contemporary combinatorial chemistry is given. The third section, containing contributions on the preparation of heterocycles and oligosaccharides, together with two chapters on multicomponent reactions and the synthesis of natural products and similar compounds on solid support, would still be considered canonical for a book on this topic. The fourth section however, making virtual compound libraries and molecular modeling, design criteria for combinatorial libraries, ADME (absorption, distribution, metabolism, excretion) parameters or the estimation of the shelf life of compounds a subject of discussion, may, at first glance, seem somewhat unusual for readers not used to thinking in the categories of industrial research. Nevertheless, this section and particularly the chapter describing the development of erythropoietin sensitizers is eminently suited for introducing the novice to the process of drug development. Finally, section 5 gives an overview over new trends in the field of combinatorial sciences, with a focus on both process development and catalyst discovery. The last two chapters on combinatorial aspects of materials science and the interface of combinatorial chemistry and biochemistry are a nice finish, highlighting interdisciplinary approaches which bridge gaps to the neighbouring fields of solid state physics and biology.

Unfortunately, some of the pictures presented (e.g. in chapter 6) are of low quality and in some chapters important examples of reactions or methodology are missing, such as the ¹⁹F-tags developed by Pirrung et al. Moreover, some of the contributions contain considerable numbers of self-citations and appear more like an account than like a book chapter. Considering the large number of authors and independent contributions, a certain degree of redundancy cannot be prevented; a striking example is, however, the benzopyran synthesis developed by one of the editors – this reaction is not only mentioned but also depicted in seven different chapters. Certainly the most conspicuous problem is the high price of the book which may even be prohibitive for libraries.

Despite all criticism, this book is a valuable and rich source of information on state of the art combinatorial chemistry in both industry and academia. It can be used as an introduction to the field and provides the reader with a comprehensive overview over current applications of combinatorial methodology in research and development.

Horst Kunz and Till Opatz
Johannes Gutenberg-Universität, Germany

Carbohydrate Bioengineering: Interdisciplinary Approaches

T. T. Teeri, B. Svensson, H. J. Gilbert and T. Feizi, RSC, Cambridge, UK, x + 196 pp., £79.50, ISBN 0-85404-826-X Search PubMedThis book records the presentations given at the fourth Carbohydrate Bioengineering Meeting held in Stockholm in June 2001. The term “bioengineering” smacks of materials and indeed, the previous meeting in this series focused strongly on cellulose and starch, both of which have large scale applications in the food, textile and paper industries. However, as the range of topics discussed at this meeting shows, the term has much wider implications. To make progress in the bioengineering of carbohydrates, an understanding of the fundamental chemistry, biochemistry and biology of carbohydrates is essential. Accordingly, topics covered included structural studies, fundamental investigations on glycosidase mechanisms and the identification of carbohydrate-active enzymes in completely sequenced genomes.

The power of X-ray crystallography is strongly demonstrated in no less than seven presentations recording and describing structures of carbohydrate-metabolising enzymes, kicked off by a survey on the structural enzymology of carbohydrate-active enzymes (G. Davies). There follow six contributions on, respectively, hyaluronidase, α-1,2-mannosidases of glycoprotein biosynthesis, lytic transglycosylases, a retaining galacotosyltransferase, amylosucrase and malto-oligosyl trehalose synthase. Structural studies have strongly informed mechanistic work and this is reflected in the chapters by D. L. Jakeman and S. G. Withers in which is described the engineering of glycosidases for synthetic purposes that the understanding of glycosidase mechanisms have made possible, a theme continued in the chapter by B. Svensson et al. on glucoamylases.

The big-league carbohydrates, starch and cellulose are still well to the fore. Given the state of ignorance about cellulose and starch biosynthesis and hydrolysis a few years ago, astonishing strides have been made recently in understanding their biochemistry. Advances have been strongly aided by molecular biological and structural studies. To see this for themselves, the reader should go to the chapters “An update on carbohydrate binding molecules” (H. J. Gilbert et al.) and the chapter on glucoamylases mentioned above. The titles of these two chapters themselves reflect the enormous progress made and the desirability of standing back to take a look at the present picture to see where future research should be directed.

It is appropriate that towards the end of the book, genome sequences should be recognised as pinpointing potential carbohydrate metabolising enzymes. Bernard Henrissat's classification of “carbohydrate-active enzymes” has proved to be a powerful tool for comparisons of different classes of enzyme and in his chapter he presents a global survey of such proteins in eighteen completely sequenced genomes.

The very existence of the “Carbohydrate Bioengineering” conferences highlights the current status of the synthesis and modification of carbohydrates. For the other major classes of biopolymer, peptides and oligonucleotides, automated synthesis is now routine; for carbohydrates, it is still a distant goal. Despite the huge strides made in methods for the non-biological synthesis of carbohydrates, oligosaccharide synthesis and carbohydrate polymer modification using these methods are still hugely problematic. It is therefore somewhat disappointing to find only three chapters in this book on chemo-enzymatic carbohydrate modification, and only one of these (by Monica Palcic et al.) addressing properly the synthesis of small, biologically active oligosaccharides. Perhaps this deficiency will be remedied at the next conference in the series.

David Crout
Warwick, UK

Pharmaceutical Chemistry

Christine M. Bladon, Wiley, UK, 2002, xii + 221 pp., price £24.95, ISBN 0-471-49637-5 Search PubMedThe continuing increase in the teaching of medicinal and pharmaceutical chemistry, either as part of a chemistry degree or as a separate course, has resulted in the publication of a number of medicinal chemistry textbooks of variable quality. Perhaps understandably, these books have usually centred on ‘small molecules’, which currently comprise the majority of marketed drugs. However, recent innovations in synthetic chemistry and molecular biology have resulted in the emergence of biomacromolecules as drugs, and it is these higher molecular weight compounds that form the subject of this book.

The book is derived from a series of final-year undergraduate lectures presented by the author, and comprises an introductory chapter, followed by five subject chapters. These cover endogenous peptides and proteins and their modification, therapeutic aspects of the immune system, oligonucleotides in gene- and antisense-therapy, and oligosaccharides. A concise overview of the medicinal chemistry and molecular biology associated with each class of biomacromolecule is given, and several contemporary examples of drugs are provided. The inclusion of examples of monoclonal antibodies and antibody-toxin conjugates for the treatment of cancer, and of antisense molecules as antitumour and antiviral agents, is particularly timely. Although a number of related approaches, including antibody-directed enzyme prodrug therapy (ADEPT) for cancer, are not mentioned, overall the book provides an excellent introduction to biomacromolecules as therapeutic agents. Each chapter concludes with an extensive list of further reading and research publications, and a useful appendix and glossary provide a summary of the basic biochemistry and terminology relating to each class of biomacromolecule.

Medicinal and pharmaceutical chemistry students will certainly find this book informative and good value, as will those studying related subjects at the chemistry–biology interface. However, a basic understanding of biochemistry and molecular biology is required, and the book may be more appropriate reading material for postgraduate-level degree courses. This book will also be of wider interest to chemists who wish to gain a better understanding of molecular biology and pharmaceutical biotechnology.

Roger J. Griffin
Northern Institute for Cancer Research, University of Newcastle upon Tyne, UK

Alkaloids – Nature's Curse or Blessing?

Manfred Hesse, Wiley-VCH, UK, 2002, xii + 413 pp., price £75, ISBN 3906390241 Search PubMedThe one question not answered in this otherwise excellent book is – ‘Curse or Blessing?’ Most police forces would undoubtedly claim that cocaine and heroin were a curse, though the value of these alkaloids as local anaesthetic and analgetic are beyond dispute. Comparison of use and abuse quickly becomes tedious, and a contemporary view would surely err on the positive side. While the number of naturally occurring alkaloids in clinical use is relatively small – morphine, vinblastine, vincristine, quinine, and a few others – many alkaloids have provided the skeletal basis for the design of pharmacologically more useful compounds, e.g. pethidine, buprenorphine, verapamil, mefloquine, etc. After a decade of dedication to combichem., the pharmaceutical industry is rediscovering the benefits of using Nature's own two billion year exploration of combichem. in higher plants, to identify key alkaloids (and other natural products) as lead structures for drug discovery.

Manfred Hesse is eminently qualified to write about alkaloids having spent much of his life working with them. His great knowledge and affection for this class of natural products shines through every page. He begins with a fascinating etymology of the word alkaloid and provides a masterly 100 page classification of this family. Indeed this chapter and the next one on structure elucidation could stand alone as a comprehensive introduction to the area. The classical methods of structure determination are illustrated by the 19^th century work on coniine, and the elucidation of the structure of villalstonine is used to show how modern techniques are used to solve complex structures. There is an amusing interlude for a discussion of artefacts produced during isolation or purification of alkaloids, and the chiroptical properties of alkaloids also merit a short chapter; then the second half of the book is devoted to synthesis, chemotaxonomy, biogenesis, and the biological–ethnopharmacological importance of alkaloids. This should be the best part of the book, but although the chemotaxonomy is very good, the chapters on synthesis and biogenesis are very selective. Almost all of the illustrative syntheses are 25 or more years old, so the reader gets no idea of the elegant chemistry that is used in contemporary alkaloid synthesis; and only the biogenesis of the benzylisoquinoline alkaloids is described.

The last three chapters cover the biological significance of alkaloids, some historical aspects (mainly brief mention of the main pioneers – Serturner, Pelletier, Robinson, Woodward, etc.), and a long account of those alkaloids that have particular cultural significance. This last chapter is particularly good and beautifully illustrated. All of the old favourites are discussed: hemlock, fly agaric, ergot, opium etc., with a lot of quotations from historical sources and superb figures.

Overall this is a very personal account of the alkaloids and could best be described as a very handsome book for the coffee table rather than one for the reference library.

John Mann
Queen's University, Belfast, UK

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