Solid-Phase Synthesis and Combinatorial Technologies

by Seneci, Pierfausto

• ISBN13: 9780471331957
• ISBN10: 0471331953
• Edition: 1st
• Format: Hardcover
• Copyright: 2000-07-11
• Publisher: Wiley-Interscience

Summary

A unique, integrated look at solid-phase synthesis and advances in combinatorial chemistry and technologies The last decade has seen a rapid expansion in combinatorial technologies, a field where chemistry disciplines intersect with automation, statistics, and information science, as well as certain biological disciplines. Reflecting these multidisciplinary trends, this new work provides a comprehensive overview of the most important aspects of solid-phase synthesis (SPS), combinatorial chemistry, and related combinatorial technologies. It clearly demonstrates how SPS and combinatorial chemistry have extended their application from the pharmaceutical arena to new areas, including biotechnology, material sciences, catalysis, and agrochemical industries, and explores in detail strategies for planning, designing, preparing, and testing of combinatorial libraries in various disciplines. Designed to meet the needs of both experienced combinatorial chemists and newcomers to the field, Solid-Phase Synthesis and Combinatorial Technologies: Surveys the most recent developments in SPS and combinatorial chemistry Explains the entire process, from determining the need for a library to the details necessary for synthesis of the library Discusses choice of format, size, and the rationale behind the design of each synthetic step Surveys the analytical techniques and the purification methods used to characterize and purify combinatorial libraries Employs a large number of examples to illustrate important concepts Includes problems geared toward applying acquired knowledge and designing the steps to SPS/library synthesis Describes the quality control and activity screening of combinatorial libraries for various applications Features a detailed bibliography of more than 1,700 relevant sources

Author Biography

<b>PIERFAUSTO SENECI, PhD</b>, is Associate Director of Chemistry at the Glaxo Wellcome Medicines Research Centre, Verona, Italy.

Table of Contents

Preface	ix
Solid-Phase Synthesis: Basic Principles	1	(44)
Solid Supports	1	(8)
Linkers	9	(17)
Reaction Monitoring in Solid-Phase Synthesis	26	(7)
Purity and Yield Determination in Solid-Phase Synthesis	33	(12)
References	38	(7)
Solid-Phase Synthesis: Oligomeric Molecules	45	(46)
Peptides	45	(12)
Oligonucleotides	57	(14)
Oligosaccharides	71	(20)
References	84	(7)
Solid-Phase Synthesis: Small Organic Molecules	91	(45)
Small Organic Molecules on Solid Phase: Target Selection and Solution Studies	92	(1)
Small Organic Molecules on Solid Phase: Solid-Phase Synthesis	93	(3)
Small Organic Molecules on Solid Phase: From Solid-Phase Synthesis to Synthetic Organic Libraries	96	(2)
An Example: Solid-Phase Synthesis of 1H-[2] Pyrindinones	98	(9)
Solid-Phase Synthetic Strategies: Selected Examples	107	(29)
References	134	(2)
Combinatorial Technologies: Basic Principles	136	(29)
Combinatorial Technologies	136	(6)
Combinatorial Libraries	142	(23)
References	162	(3)
Synthetic Organic Libraries: Library Design and Properties	165	(45)
Primary Libraries: Shooting in the Dark?	165	(5)
Focused Libraries: High-Throughput Structure--Activity Relationships	170	(4)
Biased-Targeted Libraries: Information-Rich Primary Libraries	174	(2)
Library Design via Computational Tools	176	(34)
References	204	(6)
Synthetic Organic Libraries: Solid-Phase Discrete Libraries	210	(54)
Synthesis of Solid-Phase Discrete Libraries	210	(5)
Structure Determination, Quality Control, and Purification of Solid-Phase Discrete Libraries	215	(9)
Examples of Solid-Phase Discrete Library Synthesis	224	(22)
New Trends in Solid-Phase Discrete Library Synthesis	246	(18)
References	255	(9)
Synthetic Organic Libraries: Solid-Phase Pool Libraries	264	(75)
Synthesis of Solid-Phase Pool Libraries	264	(15)
Direct Structure Determination of Positives from Solid-Phase Pool Libraries	279	(11)
Deconvolution Methods for Solid-Phase Pool Libraries	290	(11)
Encoding Methods for Solid-Phase Pool Libraries	301	(17)
New Trends in Solid-Phase Pool Libraries	318	(21)
References	328	(11)
Synthetic Organic Libraries: Solution-Phase Libraries	339	(83)
Solution-Versus Solid-Phase Synthetic Libraries: Which Ones to Use?	339	(7)
Solution-Phase Discrete Libraries	346	(15)
Purification of Solution-Phase Library Intermediates and Final Compounds: Liquid--Liquid and Solid-Phase Extraction Systems	361	(11)
Solid-Phase Assisted Solution-Phase Library Synthesis and Purification	372	(25)
Soluble Supports in Solution-Phase Combinatorial Synthesis	397	(7)
New Trends in Solution-Phase Combinatorial Synthesis	404	(18)
References	410	(12)
Applications of Synthetic Libraries	422	(84)
Pharmaceutical Applications	422	(32)
Agrochemical and Food-Related Applications	454	(2)
Applications to Combinatorial Reaction Optimization	456	(4)
Applications to Catalysis	460	(24)
Applications to Molecular Recognition	484	(22)
References	497	(9)
Biosynthetic Combinatorial Libraries	506	(73)
Biosynthetic Polypeptide Libraries	506	(24)
Biosynthetic Oligonucleotide Libraries	530	(22)
Combinatorial Biosynthesis of Natural Products	552	(10)
Combinatorial Biocatalysis	562	(17)
References	567	(12)
Materials and Polymeric Combinatorial Libraries	579	(42)
Synthesis of Materials Science Libraries	579	(9)
Characterization and Screening of Materials Science Libraries	588	(12)
Polymeric Combinatorial Libraries	600	(21)
References	615	(6)
Index	621