Book Reviews

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Specialist Periodical Report: Organophosphorus Chemistry, Volume 30

Senior Reporters D. W. Allen and J. Tebby, RSC, Cambridge, UK, 2000, xvi + 362 pp., price £189.50, ISBN 0-85404-324-1 Search PubMedThis volume of Organophosphorus Chemistry covers the literature from July 1997 to June 1998 (Chemical Abstracts Volumes 127 and 128) and consists of eight chapters on 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 Acids by T. P. Kee (Chapter 3), Quinquevalent Phosphorus Acids by B. J. Walker (Chapter 4), Nucleotides and Nucleic Acids by J. S. Vyle (Chapter 5), Ylides and Related Species by N. Bricklebank (Chapter 6), Phosphazenes by J. C. van de Grampel (Chapter 7), and Physical Methods by R. N. Slinn and M. C. Salt (Chapter 8). Interest in organophosphorus chemistry continues unabated. This is because of the enormous diversity and roles of these compounds in chemistry and biology. Asymmetric catalysis drives developments in tertiary phosphine chemistry; Wittig chemistry (the centenary of George Wittig’s birth occurred in 1997), developments in phosphonium chemistry. The seventieth birthday of Robert Wolf was also recognized in the year by the dedication to him of a volume of Phosphorus Sulfur and Silicon; there also appeared important review articles on calixarene phosphates and on the formation of hexacoordinated phosphorus compounds via donor interactions and the relevance of the chemistry to enzymic intermediates. A rapidly expanding area of tervalent phosphorus acid derivatives concerns the fabrication of devices based on surface-immobilised DNA. Linear, cyclo- and poly-phosphazenes and their derivatives are discussed in Chapter 7, where it is apparent that they have wide application as synthetic intermediates, bases, flame retardants, colorants, ligands, and for the synthesis of polymeric materials, and drug delivery agents. The chapter on physical methods is particularly useful, bringing together as it does a large body of important information on theoretical and spectroscopic methods and results. Because of the sophistication of much of the material, the reading of these well-written reviews is an excellent way of keeping abreast of developments in ones own and related fields. For a comprehensive coverage of the literature on these topics, this volume is highly recommended.

S. B. Wild
Australian National University, , Canberra,

Pharmaceuticals: Classes, Therapeutic Agents, Areas of Application

Ed. J. L. McGuire, Wiley-VCH, vi, viii, vi, vii + 2315 pp., price £635, ISBN 3-527-29874-6 Search PubMedThe ambitious aim of this new series is to provide authoritative coverage of pharmaceutical agents and their application for the treatment of disease symptoms. In addition it also attempts to briefly survey the pharmaceutical industry for readers not familiar with its workings.

The series is broken into four volumes, each of which deals with broadly grouped therapeutic areas and in addition the final volume contains a number of chapters that cover technical and regulatory aspects of the pharmaceutical industry. Dealing with broad therapeutic areas in turn the subject matter is broken into discrete chapters containing introductions covering disease states, drug targets and their modes of action. The level of detail here is variable and the language used will sometimes be outside the scope of general readers. Treatment of the pharmaceutical agents themselves provides a level of detail and reference material that should be useful to all readers. These include clear chemical structures, CAS registry details and relevant physical data along with trade names and manufacturers details. Mechanistic details accompany this information where appropriate and details of chemical synthesis are often included. Unfortunately it is clear in certain chapters that the authors have inserted primary material rather than refining it or searching out more up to date references. In the case of drugs derived from natural products for example, this can mean that details pertaining to classification of the producing organism are sometimes out of date.

An opening monograph by the series editor introduces the pharmaceutical industry, and provides very useful information concerning companies, markets and products. The remainder of volume 1 is dedicated to Cardiovascular Drugs with coverage of those that directly influence cardiovascular function, as well as those which influence the heart and blood vessels. Volume two deals with Neuropharmaceuticals, Gastrointestinal Drugs and Respiratory Tract Drugs and the third volume concentrates on Antiinfectives and Endocrine and Metabolic Drugs. Here, treatment of the antibiotic area, and thus the main consideration of natural products in the series, proves disappointing reading. A brief historical introduction is given and a comprehensive listing of compounds and their uses is provided. Little space however is given to dealing with issues of current importance: mechanisms of action are poorly covered, the emergence of multi-drug resistant pathogens is dealt with in short shrift while little thought is given to the future role of natural products within the industry. Although outside the scope of this series the wider challenges that natural products offer to high throughput screening, and the use of pre-fractionated libraries or similar approaches as an attempt to address this are ignored. Similarly, the application of biosynthetic engineering technologies to access new chemical diversity from natural products does not merit comment. From a personal viewpoint these omissions are an oversight. The separate treatment of antibiotics and synthetic chemotherapeutic agents also means that important semi-synthetics are ignored, although the latter chapter provides better treatment for some of the issues discussed above for antibiotics. This volume is however favoured by good coverage of HIV and AIDS therapeutics and with a very good second section from which the chapter concerning peptides and peptide hormones stands out.

The fourth and final volume in the series covers Miscellaneous Drugs and Related Technologies as well as containing the indexes. Of note in this volume are the chapters concerning immunotherapy and vaccines and monoclonal antibodies. The chapters on types of dosage forms and on drug testing will be of particular use to those readers outside the pharmaceutical industry. The latter chapter takes the reader through the issues and processes involved in taking a screening hit through to pharmaceutical agent, although much more weight is given to the downstream part of the process and more consideration of the actual discovery process would have been beneficial (a general criticism with the series).

Overall there is a great deal of interesting material in this series that should provide a useful introduction to those interested in the pharmaceutical industry, as well as a source of information to those it already employs. It is a shame that chapter quality is quite so varied, but probably not unexpected given the tremendous variation of topics and the number of chapters required to cover these. The lack of space given over to a consideration of the discovery process is a great pity. Overall the series does represent a useful introduction and reference guide to pharmaceutical classes and therapeutic agents as intended, and to a lesser degree to the pharmaceutical industry in general.

Barrie Wilkinson
Biotica Technology Ltd, , UK

Amino Acids, Peptides and Proteins

J. S. Davies, Senior Reporter, Specialist Periodical Reports, Royal Society of Chemistry, Cambridge, Volume 30, 1999, xvi + 398 pp., £159.50, ISBN 0-85404-222-9; Volume 31, 2000, xvi + 446 pp., £179.50, ISBN 0-85404-227-X Search PubMedThese are the thirtieth and thirty-first annual volumes of this excellent Specialist Periodical Report. They update coverage of the literature in the field to the end of 1997 and of 1998 respectively. Volume 30 contains five chapters, the four “core chapters” reviewing (i) amino acids, (ii) peptide synthesis, (iii) biological and conformational studies on peptides, and (iv) cyclic, modified and conjugated peptides. The fifth chapter of Volume 30 is the regular biennial chapter on β-lactam chemistry. Volume 31 contains six chapters, the four “core chapters” of Volume 30 being updated and an additional two chapters reporting work on metal complexes of amino acids and peptides, and on current trends in protein research. Between them, the reviewers have cited 3,053 references to the literature in Volume 30 and 3132 references in Volume 31.

The first chapter in both volumes, as always, covers amino acids and is reported by Dr Graham Barrett. The chapter follows a familiar pattern in both volumes. After a brief introduction and discussion of review articles and books, the isolation of known and new amino acids from natural sources and from hydrolysates of naturally occurring peptides is discussed. There is a large section on the synthesis of racemic and homochiral natural and “unnatural” amino acids, reflecting the growth of interest in this important area. It includes enantioselective synthesis and the use of enzymes in synthesis. Resolution of DL-amino acids by a variety of methods is covered. A section on physico-chemical studies of amino acids covers X-ray crystal structure, NMR spectroscopy, optical rotatory dispersion and circular dichroism, mass spectrometry, molecular orbital calculations, and other methods, including host–guest studies. Chemical studies of amino acids are covered, as are analytical methods such as GLC, TLC, HPLC, ion exchange chromatography and capillary zone electrophoresis. Assays for specific amino acids involving colorimetric, spectroscopic, chemiluminescence and electrochemical methods are covered and many of these involve the use of enzymes.

Dr Donald Elmore is reporter in both volumes for the second chapter covering peptide synthesis. Although new techniques for peptide synthesis are becoming less numerous, applications of peptide synthesis increase. The reporter has covered this topic in both volumes in a commendably brief manner, while still allowing the reader comprehensive access to the 1997 and 1998 literature. This has been achieved by listing the syntheses reported in appendices according to peptide name and literature citation. Amino, carboxy and side-chain protection are discussed, as are disulfide bond formation, peptide bond formation, use of solid supports, combinatorial synthesis, and enzyme mediated synthesis and semi-synthesis.

Dr Anand Dutta is reporter for the third chapter in both volumes. This describes analogue and conformational studies on peptides, hormones and other biologically active peptides. The chapter is written from the point of view of a medicinal chemist, and includes the relationship between structure and biological activity. Rigid di- and tri-peptide turn mimetics, aminomethylene, hydroxyethylene, dihydroxyethylene and hydroxyethylamine analogues, double bond and ketomethylene isosteres, and retro- and retro-inverso pseudopeptides are covered and cyclic peptides are discussed. A considerable section of the chapter in both volumes is devoted to biologically active peptides, which are grouped according to the diseases to which they relate, or to the parent peptide for which they are analogues. There is also considerable discussion of enzyme inhibitors, phage library leads and inhibitors of protein–protein interaction.

Chapter 4, written by the senior reporter in both volumes, discusses cyclic, modified and conjugated peptides. These are described in terms of isolation from natural sources, synthesis, and biological, chemical and physical properties. The series from cyclodipeptides to cyclododecapeptides is described and there was particular activity in research on cyclopentapeptides in 1997. Cyclodepsipeptides, phosphopeptides and lipopeptides are discussed and prominence is given to the considerable amount of research on glycopeptides.

Chapter 5, the final chapter of Volume 30, reported by Professor Christopher Schofield, is the biennial discussion of β-lactam chemistry, work from 1996 and 1997 being covered. Attempts to combat bacterial resistance have led to a continuing interest in developing new β-lactam antibiotics but new structural variants are rare. The significant progress in elucidating β-lactam biosynthesis continues and genetic and X-ray results have given a greater understanding of the mechanism of penicillin biosynthesis. Work on cephalosporin, clavam and carbapenem biosynthesis is also described as is the continuing work on class A, B and C β-lactamases. The remainder of the chapter describes work on the synthesis, chemistry, structure–activity relationships and physical and theoretical studies on the various known classes of β-lactam antibiotics and their analogues and of simpler azetidinones.

Chapter 5 in Volume 31, written by E. Farkas and I. Sóvágó, covers work done on metal complexes of amino acids and peptides and related ligands in 1997 and 1998. As in previous volumes, the papers are classified under the three headings (i) synthesis and structural studies, (ii) solution equilibria, and (iii) reactivity and kinetics. The increasing interest in bio-inorganic chemistry makes this chapter of increasing importance.

Chapter 6 in Volume 31 on current trends in protein research is written by the protein crystallographer Jennifer Littlechild and covers the literature for 1997 and 1998. The wealth of information available has meant that she has had to be selective in her coverage but she has included topics such as the importance of protein conformation in disease, human proteins, protein chaperonines, enzyme catalysis, RNA and DNA binding proteins and metalloproteins.

These volumes, although relatively expensive, present a comprehensive review of important science at the chemistry/biology interface and will be welcomed by chemists, biochemists and medicinal chemists as a way of updating their knowledge. The literature coverage is very comprehensive which probably accounts for the fact that, although the volumes have cut-off dates for literature coverage of the end of 1997 and 1998 respectively, they were not published until 1999 and 2000 respectively.

Douglas Young
Sussex University

Biosynthesis: Aromatic Polyketides, Isoprenoids and Alkaloids

Vol. 209 of “Topics in Current Chemistry”, Eds. F. J. Leeper and J. C. Vederas, Springer, Berlin, 2000, viii + 247 pp., price £93, $159, ISSN 0340-1022, ISBN 3-540-66573-0 Search PubMedDespite the challenges of combinatorial chemistry, natural products unquestionably continue to provide the prime source of molecular diversity. Nature has been exploring molecular space long before the term or the practice became fashionable, and any glance at a selection of natural products will reveal structural complexity and novel combinations of atoms that are beyond the bounds of the imaginations of even the most fevered synthetic chemists. The study of how these compounds are produced in nature, by plants and microorganisms, has long been a major area of study and has provided the driving force for developments in analytical techniques (both separation and spectroscopic), mechanistic studies and labelling methodology. Biosynthetic chemists have rapidly accumulated the new skills of protein chemistry and molecular genetics to pursue their quest for understanding how these complex molecules are constructed in living cells, and this has led to a fresh resurgence in natural products chemistry with the realisation that, with a full understanding of the chemical events related to the genes that control the chemistry, these can be used to manipulate the genetic structure to introduce rational changes to the structure of the molecules. This new concept of “combinatorial biosynthesis” thus has the huge potential, now being realised in some areas, to further extend the diversity already produced by nature.

The three major biosynthetic pathways are the polyketide, terpenoid and alkaloid pathways and these are the subject of this collection of comprehensive and authoritative reviews. In the first of these, Shen provides an excellent and up-to-date review of the current state of play with aromatic polyketides in bacteria, fungi and higher plants. The review concentrates on recent work at the genetic and biochemical level, and provides by far the best overview of the flood of publications that have appeared in the area in the last ten years. It discusses the details of polyketide assembly, the role of the several enzyme components in and associated with aromatic polyketide synthases and provides a detailed account of and possible explanation for some of the conflicting results that have been reported.

The assembly and cyclisation of the linear isoprenoid precursors to the mono-, sesqui- and diterpenes have been a source of study and fascination for many years. In this chapter, Davis and Croteau provide a really comprehensive overview of the enzymology and mechanisms of the terpenoid cyclases. The molecular cloning, expression and sequence analysis allied to emerging X-ray structural information are providing a real understanding of how the cyclisations are controlled at a molecular level, and ultimately how they may be manipulated.

The isoprenoid building block, dimethylallyl disphosphate, is used to introduce the branched C₅-prenyl residue into many metabolites whose basic skeletons are derived from other biosynthetic pathways. In the most substantial chapter in the volume, Williams, Stocking and Sanz-Cervera present a major and comprehensive review of biosynthetic and related mechanistic studies on the wide range of prenylated alkaloids derived from tryptophan. These are all fungal metabolites e.g. paraherquamides, brevianamides, roquefortine, echinulin, verruculogen, cyclopiazonic acid and the ergot alkaloids. This is the first detailed review of these families of compounds to have been written and has the extra value of an addendum in which recent work on the biosynthesis of tryptophan and the deoxy-xylulose pathway to DMAPP is described.

In the two final chapters, Hemscheidt provides a summary and discussion of studies on the tropane alkaloids and Hartmann and Oder discuss the biosynthesis and metabolism of the pyrrolizidine alkaloids in plants and their insect herbivores. Both articles will be of great use to those interested in the non-aromatic alkaloids and are of equal interest to non-specialists.

Overall, the volume is an invaluable addition to the natural products library and can be warmly recommended to all with an interest in and enthusiasm for biosynthesis and natural products chemistry at its best.

T. J. Simpson
University of Bristol

Fine Chemicals through Heterogeneous Catalysis

Ed. R. A. Sheldon and H. van Bekkum, Wiley-VCH, 2001, xxv + 611 pp., price £95, ISBN 3-527-29951-3 Search PubMedThe contents are better than the title. The 611 page book gives in 11 chapters a detailed compilation of the state of the art of heterogeneous catalysis in organic synthesis. A great number of authors have contributed to the book, i.e. a total of 80, of which over 25 are from industry.

After a rather short introduction by the editors on fine chemicals and catalysis an extensive overview of basic principles (43 pp.) is given including a survey of reactor types. Solid-acid and solid-base catalysts are presented in much detail including their preparation, characteristics and analysis.

The subsequent 8 chapters are divided into several sections, each dealing with one particular reaction. In total 40 different reactions are covered, mostly well known reactions, including many name reactions such as Friedel–Crafts, Diels–Alder, Heck, Aldol, Knoevenagel, classical electrophilic aromatic substitutions and several oxidations and reductions. Most sections give a lot of details about the catalyst (including its preparation), a number of applications and sometimes details of the reactor and the required process technology are given. Most sections are rather short (4–10 pp.) but do have a relevant number of references allowing a quick overview of a particular reaction. An extensive list of contents and an adequate subject index allow quick access to the several reactions and catalysts treated.

A title with Fine Chemicals promises a focus on industrial applications. Also, fine chemicals are associated with complex molecules containing several functional groups, in which chirality is often a common characteristic. In this way the title does not describe the contents. The examples given are in many cases straightforward organic reactions leading to relatively simple molecules with one or two functional groups. In fact, most products mentioned would be treated as bulk chemicals rather than fine chemicals. Pineneoxide, citral, a number of sugars and the examples of the Heck reaction are the best representatives of fine chemicals in the book. Also chirality is covered in a mere 2–3 pages.

Despite this criticism the book gives a wealth of information on heterogeneous catalysis in organic chemistry, although all information is restricted to laboratory scale research. In particular the large amount of information on the catalysts itself should be appreciated. As correctly pointed out by the editors in their concluding chapter (Future Outlook) catalysis in fine chemical industry is still in its infancy. Most examples are still heavily connected to petrochemicals and bulk chemicals. A lot more research has to be done to extend (heterogeneous) catalysis to the heart of the fine chemical industry where increasingly complex molecules (mostly heterocycles and peptide-like compounds), containing three or more functional groups and one or more chiral centers, are coming to the market. In fact, the book can well be seen as the conclusion of an era in which principles and experiences of heterogeneous catalysis originating from petrochemicals have been translated to fine chemicals. A new generation of catalysts and catalysis is needed to deal with the multifunctional and chiral molecules of the fine chemical industry of today and tomorrow. This book can well be used as a stimulant towards this new type of catalysis (which would be a merger of biocatalysis and chemocatalysis) and can therefore be recommended to both industrial and academic libraries.

Alle Bruggink
, , Nijmegen,

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