Solid-Phase Synthesis and Combinatorial Technologies

SOLID-PHASE SYNTHESIS AND COMBINATORIAL TECHNOLOGIES

INDEX

Acylsulfonamides, solution-phase combinatorial libraries of, 373

3-Acyltetramic acids, SP combinatorial libraries of, 235

Adenosine, combinatorial biocatalytic libraries from, 564

Alanine scans, 522

Aldehydes, SP combinatorial libraries of, 235

Alkaloids, SP combinatorial libraries of, 235 Alkenes, solution-phase combinatorial

libraries of, 406 Ametryn, 612, 613

Amides, solution-phase combinatorial libraries of, 341, 369, 373

Amides, SP combinatorial libraries of, 298, 455, 456

Amidinonaphthols, SP combinatorial libraries of, 235, 295

Amidinophenoxypyridines, SP combinatorial libraries of, 234

Amines, solution-phase combinatorial libraries of, 369, 375, 376, 386, 391

Amines, SP combinatorial libraries of, 235 β-Aminoalcohols, solution-phase

combinatorial libraries of, 342, 369, 371, 374

β-Aminoesters, solution-phase combinatorial libraries of, 378

Aminoglycosides, 350, 536 Aminohydantoins, SP combinatorial

libraries of, 242 3-Aminoimidazolidinones, solution-phase

combinatorial libraries of, 398 3-Aminoimidazo[1,2-a]pyridines,

solution-phase combinatorial libraries of, 369

β-Aminoketones, solution-phase combinatorial libraries of, 378

Aminopyrazolines, SP combinatorial libraries of, 234

Amorphous microporous mixed oxides (AMMs), 588

Analytical characterization of combinatorial libraries, 168, 172, 173, 215, 218, 233, 264, 272–275, 431,442, 579, 587. See also Quality control of combinatorial libraries

detection systems, 216 chemiluminescence nitrogen detection,

218, 372

evaporative light scattering (ELS), 218, 372, 436

multiple, 218–220 MS, 218, 372

NMR, flow probes in, 220 UV, 218, 220, 372

on-bead, 168, 274 NMR, 277

in solution, 168, 215, 274, 277, 320, 340 capillary electrophoresis, 214, 342 capillary LC, 218

FAB-MS, 321

flow injection analysis (FIA)/MS, 218, 220, 274, 320

Fourier Transform ion cyclotron resonance (FTICR)/MS, 218

gas chromatography (GC)/MS, 274, 394 HPLC, 216, 218, 274, 320

ultrafast gradients, 220 HPLC/MS, 215, 216, 233, 274, 321,

324, 375 HPLC/NMR, 220, 274, 436

size exclusion chromatography (SEC), 600

supercritical fluid chromatography (SFC)/MS, 218

synchrotron X-ray microbeam, 598

621

622 INDEX

Analytical characterization of combinatorial libraries (Continued)

TLC, 320

transmission electron microscopy (TEM), 600, 601

Androstanes, solution-phase combinatorial libraries of, 350

Anilides, SP combinatorial libraries of, 486 Antibodies, 517. See alsoAntibodies’

discovery, phage display, biosynthetic combinatorial libraries

catalytic, 424, 508

Antisense oligonucleotides, 424 Applications of combinatorial libraries,

422–505 agrochemical, 422, 454–456

fungicides, 454 herbicidals, 455, 456 insecticidals, 454 pesticides, 454

catalytic, 422, 460–484

drug discovery, see Pharmaceutical, applications of combinatorial libraries

food-related, 422, 454, 455 flavors, 454, 455

molecular recognition, 422, 484–497 pharmaceutical, 422–454

chemical development, 452 disease selection, 423

hit identification, 430, 431 hit to lead, 437–439

lead optimization, 452 pharmacokinetics, 452 potency, 452

safety, 452 selectivity, 452

target identification, 424

data mining, bioinformatic, 424 differential gene expression (DGE),

424 proteomics, 424

target selection, 424 target validation, 424

functional gene analysis (FGA), 424 gene overand underexpression,

424

transgenic animals, 424

Aptamers, 141, 424

Arrays, see Discrete, combinatorial libraries; Focused, combinatorial libraries

4-Aryl-1,4-dihydropyrimidines, SP combinatorial libraries of, 486

Aryl ethers, solution-phase combinatorial libraries of, 373, 374

Aryloxy alcohols, solution-phase combinatorial libraries of, 378

3-Aryloxy-2-propanolamines, solution-phase combinatorial libraries of, 342

Arylpiperazines, solution-phase combinatorial libraries of, 342

Arylsulfonamides, solution-phase combinatorial libraries of, 397

Atrazine, 612, 613 Automation, see Equipment for

combinatorial library synthesis and characterization

Azasugar peptide conjugates, SP combinatorial libraries of, 295

Balanol, solution-phase combinatorial libraries inspired by, 155

Bcl-2, 520

Benzimidazoles, SP combinatorial libraries of, 235

1,4-Benzodiazepine-2,5-diones, SP combinatorial libraries of, 142, 149, 235–240, 350

Benzodioxanes, solution-phase combinatorial libraries of, 374

Benzofurans, solution-phase combinatorial libraries of, 374

Benzopyrans, SP combinatorial libraries of, 167, 228–234, 308–310

Benzothiophenes, SP combinatorial libraries of, 235

Benzoxazines, solution-phase combinatorial libraries of, 373

Benzoxazinones, solution-phase combinatorial libraries of, 383

Bergenins, combinatorial biocatalytic libraries from, 564–567

Biaryls, solution-phase combinatorial libraries of, 343, 367

Bicyclic solution-phase combinatorial libraries, 435

Bicyclo[2.2.2]oct-5-ene-2,3-trans dimethanol (BOD), combinatorial biocatalytic libraries from, 563, 564

Biosynthetic combinatorial libraries, 137, 157–160

bacterial display, 508

in vitro translation/transcription (IVTT), 507

puromycin-driven peptide-RNA system, 507

ribosome display, 507 oligonucleotide, 141, 158, 530–552

amplification protocols, 530–544, 546, 549, 550

error-prone PCR, 544

in vitro, polymerase chain reaction (PCR) for, 532, 534, 535, 539, 543, 544, 546, 549, 550

in vivo, 532

for aptamers’ discovery, 530, 534–537 modified, 533, 537, 538 phosphorothioates, 533

for ribozymes’ discovery, 530, 531, 539–552

for C-C bond formation, 530, 550, 551

for ester hydrolysis, 530, 551

for oligonucleotide-related activities, 530, 539–545, 547–550

for peptide-related activities, 530, 545–547

synthetic protocols, automated, 531 transcription protocols, 531, 534, 535,

537, 540, 544, 546, 550 modified, 550

reverse transcriptase for, 531, 534, 535, 536, 544, 546, 550

RNA polymerase for, 531, 534, 535 in vitro selection protocols, 530, 531,

533–546, 548–551 selection-reflection strategy, 538, 539 stringency, 531, 540, 546, 549, 550 yields, 531

in vivo selection protocols, 537 peptide, see Phage display, biosynthetic

combinatorial libraries

INDEX 623

phage display, 141, 142, 157, 158, 286, 454, 506–530

amplification protocols, 507, 508, 512–514, 516–519, 522, 523, 525, 527, 528

for antibodies’ discovery, 521–527 catalytic, 156, 525–527 heavy-chain vector libraries, 522,

523, 525

light-chain vector libraries, 522, 523, 525

constrained, 518, 519, 521, 522 infection protocols, 509

by electroporation, 512

for small peptidic ligands’ discovery, 516, 518–520

loading, 509, 512, 514

for enzymatic substrates’ discovery, 516–518

for proteins’ discovery, 527–530 cloning of ligand targets (COLT),

527, 528, 530 purification protocols, 514

recombinant DNA protocols in, 510, 512

redundancy, 513, 514

scaffolded, see Constrained, phage display, biosynthetic combinatorial libraries

selection protocols, 507, 512–514, 516–519, 522, 523, 525–528

by affinity purification, 508 cutoff, 514

stringency, 514

target assisted, 511, 514 viruses for, 507, 508

yeast display, 508

Biphenyls, SP combinatorial libraries of, 279 Bis(salicylaldiminato) zinc complexes,

solution-phase combinatorial libraries of, 406

Building blocks, see Monomers

Carbamates, solution-phase combinatorial libraries of, 341

Carbamoyl guanidines, SP combinatorial libraries of, 235

Catalytic combinatorial libraries synthetic organic, 422, 460–484

624 INDEX

Catalytic combinatorial libraries (Continued)

catalytic systems, enzyme-based, 466 catalytic systems, metal-based,

460–466, 473–480 enantioselective, 465, 466 hydrolytic, 465

ligand, 460, 466–471 β-aminoalcohols, 471 carboxylates, 471 diimines, 471, 484 diols, 471 disulfonamides, 471

1,2-phenylenediamine amides 471 phosphines, 466–469

Schiff bases, 469–471 substrates, 471–473

Catenane libraries, solution-phase combinatorial libraries of, 406

Chalcones, solution-phase combinatorial libraries of, 151, 342, 358–360, 433–437

Chemical genetics, 318, 328, 424–428 forward, 425–427

reverse, 427, 428 Chemical sensors, 613

electronic nose, 613, 615 fiber optic, 614 microtongue, 615

Chemical space, 174–176 Chloramphenicol, 535 Codes, see Tags

Combinatorial biocatalysis, 159, 506, 562–567

acylation, 564–566 glycosylation, 564 halohydration, 564 hydrolysis, 564–566

Combinatorial biosynthesis, 157, 159, 506, 552–562

multienzyme systems, 553

of peptides, see Nonribosomal peptide synthetases

of polyketides, see Polyketide biosynthetic combinatorial libraries

Combinatorial biotransformations, see Combinatorial biocatalysis

Combinatorial libraries, 137

analytical characterization, see Analytical characterization of combinatorial libraries

applications of, see Applications of combinatorial libraries

bead-based, 301, 307, 318–328 biased, see Focused, combinatorial

libraries

biased/targeted, 165, 174–176, 197–204, 318, 345, 430, 431

decoration, 170

discrete, 137, 149, 150, 151 enumeration of, see Data management focused, 137, 170–173, 187–197

model, 138, 168, 169, 173, 274, 323, 324, 348, 350, 355

natural product, 152–156

pool, 137, 142–144, 146, 148–150, 153, 154

primary, 137, 150, 165–170, 176–187, 213, 318, 325

modular, 151

purification of, see Purification of combinatorial libraries

QC of, see Quality control of combinatorial libraries

side products in, 168, 442

small organic molecule, see Synthetic organic, combinatorial libraries

solid-phase, 165

discrete, 210–263, 339–341, 345 pool, 264–341, 341–345, 442

solution-phase, 170, 339–421 discrete, 339–341, 345–360 pool, 339–345

structure determination, see Structure determination of combinatorial libraries

synthesis of, see Synthetic protocols for combinatorial libraries

synthetic organic, 137, 142, 149–152, 165–505

unbiased, see Primary, combinatorial libraries

virtual, 177, 178, 183, 190, 192, 204 dynamic, 405

Combinatorial technologies, 136–620 Compound collections, 140, 141, 177, 178,

425, 426

Computational library design, 165, 176–204 molecular descriptors in, 177, 178, 180

1D, topological, 180, 191 2D, 180, 181

3D, 180, 182, 189 4D QSAR, 182

pharmacophores, 182, 188, 189, 200, 430

flexible, 182 rigid, 182

selection methods in clustering, 184–186, 189

hierarchical, 186, 187 non-hierarchical, 185

compound-based, 184 dissimilarity-based, 184, 185 genetic algorithms, 189–192

genetic optimization for ligand docking (GOLD), 195–197

LUDI, 195, 197 monomer-based, 176, 178, 179 partitioning, 184, 187

simulated annealing, 189, 192–195 Consensus motifs, 519, 522, 523 Coordination complexes, 422 Cyanohydrins, solution-phase combinatorial

libraries of, 374 Cyclen-based SP combinatorial libraries,

485

Cyclohexanones, SP combinatorial libraries of, 242, 298

Cyclohexenones, solution-phase combinatorial libraries of, 435

Cyclopentanes, SP combinatorial libraries of, 279

Data management, 422, 430–433 databases, 179,

ADC, 282

CDC, 282 relational, 432

activity data, 432, 433 analytical results, 432 physicochemical properties, 432 structural information, 432

enumeration of combinatorial libraries, 178

Markush, 178, 179 reaction-based, 178, 179

INDEX 625

representation of combinatorial libraries, 178

monomer-based, 432 product-based, 432

Dehydrating agents, polymer combinatorial libraries of, 606

Dehydroaminoacids, solution-phase combinatorial libraries of, 350

Diamides, solution-phase combinatorial libraries of, 341

3,3-Diaryloxyndoles, solution-phase combinatorial libraries of, 344

Diazepines, SP combinatorial libraries of, 279

Diethylene triamines, SP combinatorial libraries of, 235

α,α,α-Difluoromethylene phosphonic acids, SP combinatorial libraries of, 234

Dihydrofurans, SP combinatorial libraries of, 235

Dihydroisobenzofurans, SP combinatorial libraries of, 235

Dihydropyridines, solution-phase combinatorial libraries of, 435

1,4-Dihydropyridines, SP combinatorial libraries of, 149, 150, 293–298

Dihydroquinolines, SP combinatorial libraries of, 279 3,6-Dihydroxytropane, combinatorial

biocatalytic libraries from, 567 Diketopiperazines, SP combinatorial

libraries of, 240, 297 Diketopiperazines, SP synthesis of, 54–56 2,2-Dimethylbicyclo[3.3.1]nonan-9-ones,

SP synthesis of, 108–114 Direct methanol fuel cells, (DMFCs), 593 Dissimilarity, see Diversity

Diversity, 137, 143, 144, 149, 165, 167, 177, 187, 188, 319, 438, 553

Drug-like properties, 197

Dynamic combinatorial libraries, 404–410, 485

kinetic, 404 ligand, 406 receptor, 406

thermodynamic, 404

Enzymes in combinatorial chemistry, see Combinatorial biocatalysis

626 INDEX

Epothilones, SP combinatorial libraries of, 155, 156

Equipment for combinatorial library synthesis and characterization,

analytical, 216 autosamplers, 218

bead pickers, 272, 327 dispensing units

multichannel, 211, 363 automated, 240, 604, 612 manual, 363 semiautomated, 240

robotic, 213, 270, 271, 327, 353, 363, 375

liquid handling, 240 HTS, automated, 430

pipettes, see Dispensing units, equipment for combinatorial library synthesis and characterization

softwares for, 213, 215, 220 synthesizers,

automated, 213, 240, 243, 271, 353, 355, 435, 460

molecular assembly plant (AMAP), 359, 360

inkjet printers, 248–251, 587 maskless array, 247 modular, 355

for parallel optimization, 243 surface suction-based, 243 tilted centrifugation-based, 243

manual, 271 multiplates, 240

multitube apparatus, 239, 240 semiautomated, 212, 355, 358

diversomer kit, 240 domino reaction block, 240 multiblock, 213, 240

valve systems, 271

Esters, SP combinatorial libraries of, 455, 456

Estradiols, SP combinatorial libraries of, 235 Evolution, 506, 563

directed, 562

Fluorous compounds

Catalysts, 364

Reagents, 364

Frameworks, see Scaffolds

Glycopeptides, SP synthesis of, 50, 52 Guanidines, solution-phase combinatorial

libraries of, 402

Hardware, see Equipment for combinatorial library synthesis and characterization

Hexahydroisoindoles, SP combinatorial libraries of, 275–279

Hexahydro-2,3a,7-triazacyclopenta[c]- pentalene-1,3-diones, SP synthesis of, 118–125

Himbacine-inspired solution-phase combinatorial libraries, 350

Hits, 166, 174, 428, 431, 437–439 Homoallylic alcohols, solution-phase

combinatorial libraries of, 365 Hydantoins, SP combinatorial libraries of,

234, 240, 279

Hydrolyzing agents, polymer combinatorial libraries of, 608

anion-exchange latexes, 608 Hydroxy quinolinones, solution-phase

combinatorial libraries of, 342

Imines, solution-phase combinatorial libraries of, 406

Iminodiacetic acid-based solution-phase combinatorial libraries, 342, 363

Indolactams, SP synthesis of, 114–118 Indoles, solution-phase combinatorial

libraries of, 402–404 Information storage, biological and

chemical, see Data management Intersectins, 528, 530

IR spectroscopy, see Purity and yield estimation in SPS and Reaction monitoring in SPS

Isopicnic solutions, 239, 271 Isoxazoles, solution-phase combinatorial

libraries of, 365

Isoxazolines, solution-phase combinatorial libraries of, 365, 434

Isoxazolines, SP combinatorial libraries of, 240

Isoxazolylthioamides, SP combinatorial libraries of, 234

Ketones, solution-phase combinatorial libraries of, 471–473

Leads, 171, 173, 192, 438, 439 Libraries, see Combinatorial libraries Lipophilicity, 180, 198

Liquid-phase combinatorial chemistry, see Soluble supports, Solution-phase synthesis

Lisobactyn, SP synthesis of, 35, 36

Macrocycles, SP combinatorial libraries of, 234

Mass spectrometry, see Purity and yield estimation in SPS and Reaction monitoring in SPS

Materials science combinatorial libraries, 137, 142, 160–162, 482, 579–600

catalysts, 579, 586, 588–595 dielectrics, 580, 585, 599 liquid crystals, 580 magnetoresistant, 581, 582, 585

photoluminescent, 579, 583–585, 587, 595–599

solar cells, 585 superconductors, 579

2,3-(Methylenedioxy)benzaldehyde, combinatorial biocatalytic libraries from, 564

Methylene malonic acids, solution-phase combinatorial libraries of, 220

Miniaturization, 210, 248, 250, 251, 253–255, 341, 587

microanalytical methods, 255 microassays for HTS, 255, 318, 326–328,

427, 430 nanodroplet, 327

small molecule printing (SMP), 327 microcapillaries, 272 microdispensers, 250, 251, 587

electrohydrodynamic pumps, 253, 254 electroosmotic valves, 253

microreactors, 314 beads as, 265 capillary tubes as, 253

microchips as, 253, 254 Moenomycin A, SP combinatorial libraries

inspired by, 148, 149

INDEX 627

Molecular recognition combinatorial libraries, 484–497

chiral resolving agents, 486, 490–497 synthetic receptors, 485, 490

tweezer receptors, guanidinium-based, 486–490

Molecular weight (MW), 180, 197 Molecularly imprinted polymers, 610. See

also Molecularly imprinted, Polymer combinatorial libraries

Monastrol, 426

Monomer(s), 10, 47, 52, 66, 96, 97, 102, 138, 149, 150, 155, 167, 169, 170, 172, 176, 178, 192, 194, 198, 226, 227, 229, 234, 241, 252, 278, 279, 320–322, 325, 346, 347, 431, 435, 448, 602

rehearsal, 138, 145, 149, 167, 168, 173, 269, 272–274, 321, 322, 347, 351, 352, 355, 357, 359, 608

sets, 138, 149, 153, 154, 156, 167, 170, 173, 176, 231, 236, 274, 302, 308, 311, 324, 344, 345, 347, 359, 383, 491, 608

virtual, 176, 178, 180, 200 Multicomponent condensations, 226, 240,

369 Passerini, 350

three-component, 224, 378 Ugi four-component, 234, 350

Multi level chemical compatibility, 199, 200 Mutagenesis

random, 539 site-directed, 525

Mutations, single point, 516

Natural products, 319, 552, 553. See also Natural products, Combinatorial libraries

modified, 553

N-(alkoxyacyl) amino alcohols, SP combinatorial libraries of, 240

Nifedipine, 293

NMR spectroscopy, see Purity and yield estimation in SPS and Reaction monitoring in SPS

Nonribosomal peptide synthetases, 557 Novel chemical entities (NCEs), 428

628 INDEX

Oligomeric synthetic combinatorial libraries, 142–149

oligocarbamates, on SP, 285 oligonucleotide, 141, 145 oligocholates, macrocyclic, in solution,

408 oligonucleotide-related, 145 oligosaccharides, 146–149

on SP, 234, 279, 290 peptide, 141, 142–144

in solution, 398

on SP, 252, 442, 454, 485, 509 peptide-related, 144, 149

peptidomimetics, in solution, 200–202, 398, 406

peptidomimetics, on SP, 234, 279, 286, 299, 480–484, 486, 490

peptidosteroids, on SP, 485 peptoids, on SP, 294, 298

Oligonucleotide analogues, SP synthesis of, 66–71

conjugated, 68–71 cyclic, 67, 68 nucleobase-modified, 66

peptide nucleic acids (PNAs), 68 phosphodiester-modified, 67

phosphoramidates, 67 phosphorothioates, 67

post-assembly transformations, 66 silicon-containing, 68 sugar-modified, 66

Oligonucleotides, SP synthesis of, 45, 57–66 automated, 57, 58, 70, 145

reaction protocols, phosphonate, 58 phosphoramidite, 58, 68, 531

coupling protocols, 65, 66 phosphotriester, 57, 58

Oligosaccharides, SP synthesis of, 45, 71–84 glycosylation technologies, 80

enzyme-based protocol, 71, 76, 77 glycal protocol, 71–73

sulfoxide protocol, 71, 74, 75 trichloroacetimidate protocol, 71, 75,

76, 80–84

Oxadiazoles, solution-phase combinatorial libraries of, 357

Oxazoles, solution-phase combinatorial synthesis of, 172, 173, 373

Oximes, solution-phase combinatorial libraries of, 406

Oxindole quinazolines, SP combinatorial libraries of, 235

Oxyamines, solution-phase combinatorial libraries of, 342

Paclitaxel esters, solution-phase combinatorial libraries of, 357

Paromomycin, 350

Patents in combinatorial technologies, 422, 439–442

structure-based, 439, 440 technology-based, 439, 441

Pd(II)-linked cages, solution-phase combinatorial libraries of, 406

Peptides, SP synthesis of, 45–50 automated, 52, 287

capping in, 287 C-terminal modified, 46 cyclic, 51, 52–56 reaction protocols

Boc-protocol, 46 coupling protocols, 48, 52 Fmoc-protocol, 46, 47, 54

Peptidomimetics, SP synthesis of, 51, 52 Peptoids, SP synthesis of, 51 Perhydrooxazinones, solution-phase

combinatorial libraries of, 350 Phagemids, 512, 521, 523

Phages,

capsid, 508, 511, 527

coat proteins, 508, 509, 511, 512, 517, 519, 523, 527, 528, 530

filamentous, 508, 513 genes, 509, 511, 512

infectivity, 508, 512, 526, 527 mosaic, 512

tips, 512 wild-type, 508, 512

Phase switching, see Work-up protocols, solution-phase synthesis

Phenothiazine amides, solution-phase combinatorial libraries of, 350

Phenylpropyl amines, solution-phase combinatorial libraries of, 369

Phosphopeptides, SP synthesis of, 50 Physico-chemical properties, 171, 216, 600

Piperazinediones, SP combinatorial libraries of, 242

Piperazines, solution-phase combinatorial libraries of, 342, 357

Piperidines, solution-phase combinatorial libraries of, 350, 357, 448–452

Polyamine conjugates, SP combinatorial libraries of, 286

Polyazapyridinocyclophanes, solution-phase combinatorial libraries of, 342

Polyenes, solution-phase combinatorial libraries of, 342

Polyethylene glycol (PEG), see Solid supports; Soluble supports

Polyketides, combinatorial biosynthetic libraries of, 160, 506, 553–562

actinorhodin synthase, 555 DEBS synthase, 555, 556, 562

modified, 557–562 iterative, 555

modules, 553, 555, 556, 558 addition, 553

deletion, 553 duplication, 553 shuffling, 558 substitution, 558, 562

multiple plasmids in, 562 rifamycin synthase, 558 tailoring enzymes in, 555

Polymerase chain reaction (PCR), 305. See also In vitro amplification protocols, oligonucleotide, biosynthetic combinatorial libraries

Polymer combinatorial libraries, 142, 600–615

artificial receptors, 579

biodegradable materials, 579, 608–610 biosensors, 579, 613–615

catalysts, 579, 606–608 copolymers, 600

GC/LC stationary phases, 579 heteropolymers, 612, 614 molecularly imprinted, 579, 610–613 reagents, 579, 603–606

Prostaglandins, SP synthesis of, 125–134 Protecting groups, 52, 94, 95

acid-labile, 48, 54, 56, 63, 64, 128 basic-labile, 64

oxidation-labile, 64

INDEX 629

photolabile, 65, 246 reduction-labile, 46

Protein-protein interactions, 175, 518, 528 Purification of combinatorial libraries, 170,

210, 211, 215, 223, 224, 272–275, 340, 345, 361–372, 391, 461

automated, 170, 172, 173, 233, 348, 352, 402

semiautomated, 173, 352

Purity and yield estimation in SPS, 1, 33–38, 95, 96

off-bead, 33, 34, 80, 102, amino acid analysis, 48 colorimetric/fluorescence, 34

Edman degradation, 48, 49, 304, 486 Fmoc reading, 33, 34, 47

on-bead, colorimetric/fluorescence, 34, 35 IR spectroscopy, 35

magic angle spinning (MAS) NMR spectroscopy, 36–38, 80, 236

two-dimensional, 37

mass spectrometry, 29–31, 48, 236 MALDI-TOF, 35, 36

Puromycin, 507

Pyrazoles, solution-phase combinatorial libraries of, 374

Pyrazolines, solution-phase combinatorial libraries of, 434

Pyrazolopyridines, solution-phase combinatorial libraries of, 454

Pyridines, solution-phase combinatorial libraries of, 435

Pyridines, SP combinatorial libraries of, 485 Pyridinium salts, SP combinatorial libraries

of, 279 Pyridinopolyamines, solution-phase

combinatorial libraries of, 342 1H-[2]Pyrindinones, SP synthesis of,

98–107

Pyrroles, solution-phase combinatorial libraries of, 395

Quality control (QC) of combinatorial libraries, 138, 139, 169, 214– 223, 272–275, 278, 302, 433. See also Analytical characterization of combinatorial libraries