Analysis and Purification Methods in Combinatorial Chemistry

469 Pages·2004·5.393 MB·English

by  Bing Yan

Analysis and Purification
Methods in Combinatorial
Chemistry
Edited by
BING YAN
A JOHN WILEY & SONS,INC.,PUBLICATION
Analysis and Purification
Methods in Combinatorial
Chemistry
CHEMICAL ANALYSIS
A SERIES OF MONOGRAPHS ON ANALYTICAL CHEMISTRY
AND ITS APPLICATIONS
Editor
J.D.WINEFORDNER
VOLUME 163
Analysis and Purification
Methods in Combinatorial
Chemistry
Edited by
BING YAN
A JOHN WILEY & SONS,INC.,PUBLICATION
Copyright © 2004 by John Wiley & Sons,Inc.All rights reserved.
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Library of Congress Cataloging-in-Publication Data:
Analysis and purification methods in combinatorial chemistry / edited by Bing Yan.
p. cm.—(Chemical analysis;v.1075)
Includes bibliographical references and index.
ISBN 0-471-26929-8 (cloth)
1. Combinatorial chemistry. I.Yan,Bing. II. Series.
RS419.A53 2004
615¢.19—dc22
2003014606
Printed in the United States of America.
10 9 8 7 6 5 4 3 2 1
CONTENTS
PREFACE ix
CONTRIBUTORS xi
PART I ANALYSIS FOR FEASIBILITY AND
OPTIMIZATION OF LIBRARY SYNTHESIS 1
CHAPTER 1 QUANTITATIVE ANALYSIS IN
ORGANIC SYNTHESIS WITH NMR
SPECTROSCOPY 3
Laura H.Lucas and Cynthia K.Larive
CHAPTER 2 19F GEL-PHASE NMR
SPECTROSCOPY FOR REACTION
MONITORING AND QUANTIFICATION
OF RESIN LOADING 37
Joseph M.Salvino
CHAPTER 3 THE APPLICATION OF SINGLE-BEAD
FTIR AND COLOR TEST FOR REACTION
MONITORING AND BUILDING BLOCK
VALIDATION IN COMBINATORIAL
LIBRARY SYNTHESIS 53
Jason J.Cournoyer,Clinton A.Krueger,Janice V.Wade,
and Bing Yan
CHAPTER 4 HR-MAS NMR ANALYSIS OF
COMPOUNDS ATTACHED TO
POLYMER SUPPORTS 71
Meritxell Guinó and Yolanda R.de Miguel
v
vi contents
CHAPTER 5 MULTIVARIATE TOOLS FOR REAL-TIME
MONITORING AND OPTIMIZATION OF
COMBINATORIAL MATERIALS AND
PROCESS CONDITIONS 87
Radislav A.Potyrailo,Ronald J.Wroczynski,
John P.Lemmon,William P.Flanagan,
and Oltea P.Siclovan
CHAPTER 6 MASS SPECTROMETRY AND SOLUBLE
POLYMERIC SUPPORT 125
Christine Enjalbal,Frederic Lamaty,Jean Martinez,
and Jean-Louis Aubagnac
PART II HIGH-THROUGHPUT ANALYSIS FOR LIBRARY
QUALITY CONTROL 137
CHAPTER 7 HIGH-THROUGHPUT NMR TECHNIQUES
FOR COMBINATORIAL CHEMICAL
LIBRARY ANALYSIS 139
Ting Hou and Daniel Raftery
CHAPTER 8 MICELLAR ELECTROKINETIC
CHROMATOGRAPHY AS A TOOL FOR
COMBINATORIAL CHEMISTRY ANALYSIS:
THEORY AND APPLICATIONS 175
Peter J.Simms
CHAPTER 9 CHARACTERIZATION OF SPLIT-POOL
ENCODED COMBINATORIAL
LIBRARIES 209
Jing Jim Zhang and William L.Fitch
PART III HIGH-THROUGHPUT PURIFICATION TO
IMPROVE LIBRARY QUALITY 253
CHAPTER 10 STRATEGIES AND METHODS FOR
PURIFYING ORGANIC COMPOUNDS
AND COMBINATORIAL LIBRARIES 255
Jiang Zhao,Lu Zhang,and Bing Yan
contents vii
CHAPTER 11 HIGH-THROUGHPUT PURIFICATION:
TRIAGE AND OPTIMIZATION 281
Jill Hochlowski
CHAPTER 12 PARALLEL HPLC IN HIGH-
THROUGHPUT ANALYSIS AND
PURIFICATION 307
Ralf God and Holger Gumm
PART IV ANALYSIS FOR COMPOUND STABILITY AND
DRUGABILITY 321
CHAPTER 13 ORGANIC COMPOUND STABILITY
IN LARGE,DIVERSE PHARMACEUTICAL
SCREENING COLLECTION 323
Kenneth L.Morand and Xueheng Cheng
CHAPTER 14 QUARTZ CRYSTAL MICROBALANCE IN
BIOMOLECULAR RECOGNITION 351
Ming-Chung Tseng,I-Nan Chang,and Yen-Ho Chu
CHAPTER 15 HIGH-THROUGHPUT PHYSICOCHEMICAL
PROFILING:POTENTIAL AND
LIMITATIONS 369
Bernard Faller
CHAPTER 16 SOLUBILITY IN THE DESIGN OF
COMBINATORIAL LIBRARIES 407
Christopher Lipinski
CHAPTER 17 HIGH-THROUGHPUT DETERMINATION
OF LOGDVALUES BY LC/MS METHOD 435
Jenny D.Villena,Ken Wlasichuk,Donald E.Schmidt Jr.,
and James J.Bao
INDEX 457
PREFACE
More than 160 volumes of Chemical Analysis: A Series of Monographs on
Analytical Chemistry and Its Applications have been published by John
Wiley & Sons,Inc.since 1940.These volumes all focused on the most impor-
tant analytical issues of their times.In the past decade one of the most excit-
ing events has been the rapid development of combinatorial chemistry.This
rapidly evolving field posed enormous analytical challenges early on.The
two most-cited challenges are requirements for very high-throughput analy-
sis of a large number of compounds and the analysis of polymer-bound
compounds.Very impressive achievements have been made by scientists
working in this field. However, there are still formidable analytical chal-
lenges ahead.For example,the development of highly parallel analysis and
purification technologies and all methods associated with analysis to ensure
combinatorial libraries are “synthesizable,” “purifiable,” and “drugable.”
For these evident reasons,I almost immediately agreed to edit a volume on
the analysis and purification methods in combinatorial chemistry when the
series editor Professor J.D.Winefordner asked me a year ago.
In the past year it has been a great pleasure for me to work with all con-
tributors.The timely development of this volume is due entirely to their col-
laborative efforts. I have been impressed with their scientific vision and
quality work throughout the year. To these contributors, I owe my very
special thanks.I also owe a great debt to my colleagues especially Dr.Mark
Irving,and Dr.Jiang Zhao for their assistance in my editorial work.Finally
I wish to thank staff at Wiley for their professional assistance throughout
this project.
Part I of the book includes six chapters describing various approaches
to monitor reactions on solid support and optimize reactions for library syn-
thesis: Lucas and Larive give a comprehensive overview of the principle
and application of quantitative NMR analysis in support of synthesis in
both solution and solid phase.Salvino describes in detail the application of
19F NMR to monitor solid-phase synthesis directly on resin support.
Cournoyer, Krueger, Wade, and Yan report on the single-bead FTIR
method applied in monitoring solid-phase organic synthesis.Guinó and de
Miguel report on HR-MAS NMR analysis of solid-supported samples.
ix