Book Reviews
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 10 3659
Book Reviews Science of Synthesis: Houben-Weyl Methods of Molecular Transformation. Georg Thieme Verlag, Stuttgart, Germany. 2005. 41627 pp. URL: http:// www.science-of-synthesis.com (Electronic Version, 48 Volumes). Price Based on Web Site and Number of Users. Science of Synthesis: Houben-Weyl Methods of Molecular Transformation is a completely new reference series that is based on the classic Houben-Weyl Methods of Organic Chemistry. Houben-Weyl is a reference work that provides access to 146 000 experimental procedures, 580 000 target compounds, and 700 000 references covering the field of organic chemistry dating back to 1835. The print version of Science of Synthesis will ultimately consist of 48 volumes containing approximately 48 000 pages covering advances in organic chemistry between the years 2000 and 2008. It is estimated that Science of Synthesis will contain 38 000 methods, 11 000 variations, 24 000 reaction schemes, and 24 000 tables and will cover 240 000 reactions. At this time, volumes 1-7, 9-17, 19, 26, and 27 are available, and 8 more volumes are scheduled for publication in 2005. The 48 volumes will be arranged in 6 categories: (1) organometallics, (2) hetarenes and related ring systems, (3) compounds with four and three carbon-heteroatom bonds, (4) compounds with two carbon-heteroatom bonds, (5) compounds with one saturated carbon-heteroatom bond, and (6) compounds with all-carbon functions. It is of great significance that Science of Synthesis is also published in an all-electronic format that can be accessed through an interactive Web interface, and this version includes access to HoubenWeyl in PDF format. The purpose of this review is to evaluate the electronic version of Science of Synthesis. The electronic version of Science of Synthesis (SOS) can be found through the Thieme Chemistry site at http://www.science-of-synthesis.com. Use of the system requires a subscription, but all of the required software resides on the Thieme server. When the page is called up, a log-in button for the site appears in the upper lefthand corner. After log-in, the initial screen consists of two frames, with the Table of Contents frame in the left column and the main screen on the right. The Table of Contents frame has an entry box for full text searching, as well as a clickable Table of Contents. The main screen has two large tabs, correlating to the Science of Synthesis volumes that have been published to date, and the Electronic Backfile, which is the scanned PDF version of the entire Houben-Weyl series. This makes this an extremely powerful search tool, since the user has access to organic chemistry literature dating back to the early 1800s. It is important to note, however, that a PDF reader such as Adobe Acrobat or Preview is required to view the backfile monographs, and many of the older Houben-Weyl PDF files are in German. Under each of the two large tabs are smaller tabs that add functionality to the Web-based program. For example, under the Science of Synthesis large tab, the small tabs are labeled Document View (displays online SOS documents in HTML format), Advanced Search
(allows for more detailed searching or structure searching), Search Result (displays hits from a search), Search History (a running log of searches during the session), and Volume Info (publication details). Searches may be initiated from the Table of Contents frame by typing in a full text string or by browsing the Table of Contents in interactive mode. To date, there are entries for 3 of the 6 categories mentioned above (organometallics, hetarenes, and compounds with two carbon-heteroatom bonds). Clicking on each category reveals the volumes that are within the categoy, each of which is also clickable. Thus, clicking Organometallics > Volume 7: Compounds of Groups 13 and 2 (Al, Ga, In, Ti, Be, ... Ba > Product Class 1: Aluminum Compounds > Product Subclass 2: Aluminum Hydrides results in a monograph entitled Aluminum Hydrides. This monograph has 14 clickable journal citations and 2 entries in the electronic backfile, and all search terms are highlighted in yellow. Selecting a citation results in a page that allows you to order the document from FIZ AutoDoc or CrossRef. Of course, you can cut and paste the citation and search your own library to retrieve the document. A text string search results in similar but more specific citations; thus, a search of theophylline results in three hits (“Purines”, with 159 references, “Purines: Synthesis by Ring Closure” reactions with 5 references, and “Purines: Oxidation of Purines with Destruction of the Aromatic System” with 2 references). Each hit also produces links to the Electronic Backfile, which when clicked produces a PDF file with the required information. Clicking Science of Synthesis on the Table of Contents frame always returns the user to the main page. Searching under the large SOS tab makes it possible to do more advanced searches based on terms with Boolean operators (and, or, not, near) or structure or substructure searching. This function is selected by clicking the Advanced Search small tab, which brings up a screen with slots for terms and a window for submitting structure queries. Searching “theophylline and reduction” in the text fields results in a single hit that was also found using the full text search in the Table of Contents frame. Structure searching is the most versatile feature, and structures can be drawn using the ChemDraw of ISISDraw browser plugins or the resident Java applett that appears in SOS. The Java applett functions in a manner similar to that of ChemDraw and allows for inclusion of a variety of common atoms and stereochemical designations. Common ring systems can be drawn with a single click after selection from the menu, and any element can be added to a structure using the interactive periodic table feature. Once structures are drawn, they are added to the search window, and searches are initiated by clicking the search radio button. Structure searching can be done in three modes: substructure, exact structure, and reaction. Thus, when R-2-hydroxyphenethylamine was searched by structure, it resulted in 38 hits as a substructure and 0 hits as an exact structure. Each hit was a monograph with clickable citations and entries
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Journal of Medicinal Chemistry, 2005, Vol. 48, No. 10
Book Reviews
from the backfile. Reaction searching is initiated by drawing reactant and product and then adding a reaction arrow. Thus, when the conversion of benzyl cyanide to phenethylamine was searched, it produced 23 hits. These hits were more general in nature and seemed to be related to transformation of the functional group more than to the structures of the reactant or product. It should be noted that structures cannot be searched in the electronic backfile, but references to the backfile materials appear in most monographs. It was also noted that structure searching performed better using Internet Explorer than with Netscape and that the system can be quirky and somewhat intolerant of mistakes in either browser. The site works best using a PC-based computer (Dell and Gateway units performed equally well). All of the functions of SOS appeared to work on the MacIntosh platform except structure searching, since structures could be drawn but not added to the search window. A more suitable MacIntosh interface is under development. In summary, Science of Synthesis: Houben-Weyl Methods of Molecular Transformation is a versatile online search tool for easily accessing valuable organic synthetic information. When all volumes are completed in 2008, this site will provide a comprehensive searchable database for organic reactions dating from the 1800s to the present day. The interface is simple to master, and with practice, efficient searches can be completed in a short time. This product is priced according to the nature of the site and the number of users, with a substantial discount for academicians. However, it is too expensive for purchase by individual investigators. I would recommend Science of Synthesis as an addition to academic and industrial libraries at any site where organic synthesis or medicinal chemistry is a major focus.
especially good discussion of combination methods, such as GC/MS and LC/MS. In addition, an introduction to electrophoresis was included in order to set up the discussion of capillary electrochromatography (CEC) that results from the combination of HPLC and capillary zone electrophoresis. There is also a very helpful new chapter on sample preparation. Another new chapter that should be helpful to students and experienced scientists is a chapter on industrial and governmental regulatory practices, which provides an excellent introduction. Each chapter is replete with references that provide access to the depth that the reader or student could be interested in for particular topics. This book is well-written and contains relatively few errors. It is a useful reference for any laboratory where chromatography is practiced. It could also be used as a textbook for an elective course on chromatography at the major or graduate level or for a specialty course at a professional meeting. It is certainly to be recommended for the library of any college or university that has laboratory science programs.
Patrick M. Woster
This book is volume 24 in the Tetrahedron Organic Chemistry Series. It provides concisely and lucidly an introduction and overview of this important topic for nonspecialists at the advanced undergraduate or intermediate level graduate student. It is easy to read and understand and yet is not superficial, so fits its intended purpose well. In addition, it is also an enjoyable “read” for chemists already familiar with the area. The figures are clear and promote understanding of the concepts being discussed. My main disappointment is the small font employed, which was a burden for some of us whose eyes are no longer young. Professor Pirrung had thought deeply about this developing science and related it philosophically to mainstream topics in a way that makes clear how it has enriched the areas that it impinges upon and suggests opportunities for further development. The topic is divided into 20 chapters, a number of which consist of only three or four pages. Following a general overview and discussion of the origin and purpose of the methodology, he reminds us that biochemical molecules are organized naturally following combinatorial principles. There follows a brief discussion of the fundamental principles of molecular evolution that are reinforced by the survival needs for efficiency and are accompanied by the self-replication features that distinguish biochemical from laboratory synthetic processes. This subject is thought-provoking for those
Department of Pharmaceutical Sciences College of Pharmacy and Health Sciences Wayne State University Detroit, Michigan 48202 JM058203R 10.1021/jm048203r
Chromatography. Concepts and Contrasts. 2nd Edition. By James M. Miller. Wiley-Interscience, Hoboken, NJ. 2005. xiv + 490 pp. 16 × 24 cm. ISBN 04714-7207-7. $94.50. This book is a comprehensive presentation of the theory and practice of chromatography in all the forms in use today. As stated by the author, “It is based on the premise that chromatography (the concepts) should be described and taught in a unified manner that emphasizes the similarities and differences (the contrasts).” The author has followed through on that premise. Because more than 15 years have elapsed since the first edition, there were many additions that needed to be included. Each chapter and each topic from the first edition were thus updated while maintaining an emphasis on column liquid chromatography. There is an
Bruce L. Currie Department of Pharmaceutical Sciences School of Pharmacy Loma Linda University Loma Linda, California 92350 JM0582120 10.1021/jm0582120
Molecular Diversity and Combinatorial Chemistry. Principles and Applications. By Michael C. Pirrung. Elsevier, New York. 2004. xiii + 175 pp. 16.5 × 24 cm. ISBN 0-08-044532-2. $60.00.
Book Reviews
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 10 3661
of us who are presently caught up too much in the pressing need to prepare libraries for rather focused pharmaceutical purposes. The evolution of combinatorial science from preexisting peptide technologies and the needs for speculative libraries of peptides to answer biological questions come next. Synthetic chemists will be interested in concise discussions of the particular stratagems that emerged to solve the unique problems and opportunities associated with this field. Construction methodologies, the nature and appropriate use of beads, linkers, and reagents, and encoding and deconvolution stratagems are clearly covered, as are the challenges and solutions involved in analysis. A segue into peptidomimetics and then into smaller molecule compound libraries perhaps of greater interest to medicinal chemists follows. Next, one finds a discussion of solution-phase multiple parallel synthesis and the related topics of solid-phase reagents, scavenger resins, and resin capture techniques. The need for conciseness makes this section a bit too brief for many readers. A brief discussion of the power of multicomponent condensation reactions (Ugi, Passerini, Bignelli) follows. Informatics, library design, and the nature of useful diversity are covered next. Microchip technology and its ever-expanding role in contemporary science are briefly and cogently described. A short section covers ancillary technologies of lesser direct application to the daily lives of synthetic medicinal chemists; such technologies in-
clude materials chemistry and catalyst design and evaluation. Phage display is not neglected either. Following a brief section on multistep combinatorial synthesis of complex molecules such as epibatidine, mappicine, and dysidiolide, this small book concludes with a two-page recapitulation emphasizing “the big picture”. The serious reader thus has an opportunity to consolidate the lessons learned. Each chapter concludes with a number of thoughtprovoking exercises, the answers to which are collected at the end of the book. A brief bibliography and a useful index bring the book to a close. In summary, this is a very accessible and enjoyable small work encapsulating a great deal of science and technology in a clear and thoughtful way. Buy it, read it, and enjoy it. Lester A. Mitscher Department of Medicinal Chemistry Combinatorial Methodology and Library Development Center of Excellence Kansas University 4010 Malott Hall 1251 Wescoe Hall Drive Lawrence, Kansas 66045 JM058218P 10.1021/jm058218p
