Analytical Techniques for Solid-Phase Organic and Combinatorial Synthesis

In the developmental phase leading to solid-phase library generation, it is essential that reactions can be efficiently and readily optimized and quantified, and this requires reliable and sensitive techniques for the analysis of solid-phase reactions. The exploding interest in different types of solid-phase chemistry is placing increased demands on the reliability, diversity and sensitivity of such analytical methods. The authors describe the most exciting developments of the past 4–5 years.

[1]  E. Gordon,et al.  Approaches to combinatorial synthesis of heterocycles: Solid phase synthesis of pyridines and pyrido[2,3-d]pyrimidines , 1996 .

[2]  Jonathan A. Ellman,et al.  SIMULTANEOUS SOLID-PHASE SYNTHESIS OF BETA -TURN MIMETICS INCORPORATING SIDE-CHAIN FUNCTIONALITY , 1994 .

[3]  Birong Zhang,et al.  Solid phase synthesis of alkenes using the horner-wadsworth-emmons reaction and monitoring by gel phase 31P NMR , 1995 .

[4]  M. Bradley,et al.  Solid Phase Chemistry: Direct Monitoring by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry. A Tool for Combinatorial Chemistry , 1995 .

[5]  W. Murray,et al.  Solid-Phase Suzuki Coupling for C−C Bond Formation , 1996 .

[6]  Matthew J. Plunkett,et al.  Solid-Phase Synthesis of Structurally Diverse 1,4-Benzodiazepine Derivatives Using the Stille Coupling Reaction , 1995 .

[7]  L. A. Randall,et al.  "Analogous" Organic Synthesis of Small-Compound Libraries: Validation of Combinatorial Chemistry in Small-Molecule Synthesis , 1994 .

[8]  P. Griffin,et al.  Microchemical structural determination of a peptoid covalently bound to a polymeric bead by matrix-assisted laser desorption ionization time-of-flight mass spectrometry , 1994 .

[9]  J. Fréchet,et al.  Solid-phase synthesis of oligosaccharides. I. Preparation of the solid support. Poly[p-(1-propen-3-ol-1-yl)styrene] , 1971 .

[10]  E. Giralt,et al.  Comparative study of supports for solid-phase coupling of protected-peptide segments , 1989 .

[11]  E. Gordon,et al.  APPROACHES TO COMBINATORIAL SYNTHESIS OF HETEROCYCLES : A SOLID-PHASE SYNTHESIS OF 1,4-DIHYDROPYRIDINES , 1996 .

[12]  J. Schaefer.  High-Resolution Pulsed Carbon-13 Nuclear Magnetic Resonance Analysis of Some Cross-Linked Polymers , 1971 .

[13]  D. Cole,et al.  Analytical Techniques for Combinatorial Chemistry: Quantitative Infrared Spectroscopic Measurements of Deuterium-Labeled Protecting Groups , 1996 .

[14]  J. Ellman,et al.  Expedient method for the solid-phase synthesis of aspartic acid protease inhibitors directed toward the generation of libraries. , 1995, Journal of medicinal chemistry.

[15]  Susanta K. Sarkar,et al.  An NMR Method To Identify Nondestructively Chemical Compounds Bound to a Single Solid-Phase-Synthesis Bead for Combinatorial Chemistry Applications , 1996 .

[16]  The solid phase synthesis of dihydro- and tetrahydroisoquinolines , 1995 .

[17]  G. Jung,et al.  Organic Chemistry on Solid Supports , 1996 .

[18]  J. Kihlberg,et al.  Use of 19F NMR spectroscopy to evaluate reactions in solid phase organic synthesis , 1996 .

[19]  M E Hemling,et al.  Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide bead-bound combinatorial libraries. , 1996, Analytical chemistry.

[20]  E. Felder,et al.  Solid support synthesis of highly functionalized pyrazoles and isoxazoles; Scaffolds for molecular diversity , 1996 .

[21]  Robert C. Anderson,et al.  Analytical Techniques in Combinatorial Chemistry: MAS CH Correlation in Solvent-Swollen Resin , 1995 .

[22]  P. Keifer.  Influence of Resin Structure, Tether Length, and Solvent upon the High-Resolution (1)H NMR Spectra of Solid-Phase-Synthesis Resins. , 1996, The Journal of organic chemistry.

[23]  S. Benkovic,et al.  A mass spectrometric solution to the address problem of combinatorial libraries. , 1994, Science.

[24]  P. Zhou,et al.  Formation of CC bond in solid phase synthesis using the heck reaction , 1995 .

[25]  Harry C. J. Ottenheijm,et al.  Solid-phase organic reactions: A review of the recent literature , 1996 .

[26]  M. J. Gardner,et al.  COMBINATORIAL SYNTHESIS : THE DESIGN OF COMPOUND LIBRARIES AND THEIR APPLICATION TO DRUG DISCOVERY , 1995 .

[27]  R. Sheppard,et al.  Solid phase peptide synthesis : a practical approach , 1989 .

[28]  P. White,et al.  Counterion distribution monitoring: a novel method for acylation monitoring in solid-phase peptide synthesis. , 1990, Biochemical Society transactions.

[29]  Paul A. Keifer,et al.  High-Resolution 1H NMR in Solid-Phase Organic Synthesis , 1994 .

[30]  Structure determination in combinatorial chemistry: Utilization of Magic Angle Spinning HMQC and TOCSY NMR spectra in the structure determination of Wang-bound lysine , 1995 .

[31]  D. Horowitz,et al.  Solvent swelling for enhancement of carbon-13 nuclear magnetic resonance spectral information from insoluble polymers: chloromethylation levels in crosslinked polystyrenes , 1980 .

[32]  C. Holmes,et al.  Methods for Combinatorial Organic Synthesis: The Use of Fast 13C NMR Analysis for Gel Phase Reaction Monitoring , 1994 .

[33]  D. Rees,et al.  Synthesis of an array of amides by aluminium chloride assisted cleavage of resin-bound esters , 1996 .

[34]  M. Lebl,et al.  Noninvasive continuous monitoring of solid-phase peptide synthesis by acid-base indicator. , 2009, International journal of peptide and protein research.

[35]  B. Yan,et al.  Probing solid-phase reactions by monitoring the IR bands of compounds on a single “flattened” resin bead , 1996 .

[36]  R. Valerio,et al.  Rapid optimization of organic reactions on solid phase using the multipin approach: Synthesis of 4-aminoproline analogues by reductive amination , 1995 .

[37]  Bing Yan,et al.  INFRARED SPECTRUM OF A SINGLE RESIN BEAD FOR REAL-TIME MONITORING OF SOLID-PHASE REACTIONS , 1995 .

[38]  S. Reich,et al.  NPIT: A new reagent for quantitatively monitoring reactions of amines in combinatorial synthesis , 1995 .

[39]  K. Chapman,et al.  Solid phase synthesis of aryl ethers via the mitsunobu reaction , 1995 .

[40]  W. Hancock,et al.  A new micro-test for the detection of incomplete coupling reactions in solid-phase peptide synthesis using 2,4,6-trinitrobenzenesulphonic acid. , 1976, Analytical biochemistry.

[41]  J. Bermak,et al.  SOLID-PHASE SYNTHESIS OF PEPTIDYLPHOSPHONATES , 1994 .

[42]  Jonathan A. Ellman,et al.  Synthesis and Applications of Small Molecule Libraries. , 1996, Chemical reviews.

[43]  B. Yan,et al.  Progression of Organic Reactions on Resin Supports Monitored by Single Bead FTIR Microspectroscopy. , 1996, The Journal of organic chemistry.

[44]  J. Adams,et al.  Use of Spin Echo Magic Angle Spinning 1H NMR in Reaction Monitoring in Combinatorial Organic Synthesis , 1996 .

[45]  J. Rizo,et al.  Application of gel-phase 13c-nmr to monitor solid phase peptide synthesis , 1984 .

[46]  R. Petter,et al.  19F NMR monitoring of a SNAr reaction on solid support , 1996 .

[47]  R. B. Merrifield,et al.  Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction. , 1981, Analytical biochemistry.