Index

A A54145,441 2-Acetylglaucarubinone, 23 1, 232 2-Acetylneriifolin, 304, 305 Aclacinomycins, 432,433 Aconitum forrestii, 237 Actinomadura verrucosospora, 43 1 Actinorhodin, 3 18, 3 19 Adrena sp., 204,205 Adriamycin, 455 Adsorption chromatography, 15-2 1,

112,113 Affinity chromatography, 19-2 1 Ajugasterone, 198, 199 Ailanthinone, 23 1,232 Alkaloid extraction and detection,

221,352,353,356,357 N-Allynorreticuline, 236 Alumina, 121, 139, 140 Amberchrom CG16 1 ,CG7 1,42 1 Amberlite, 148-l 5 1 3-Amino- 1-(2-aminoimidazolyl)-

prop-1-ene, 381,382 Ammonium reineckate, 356, 357 Analogs, generating and looking for,

425-458 Anion exchangers, 146, 147 Aphyllidine, 139, 140 Aplysinaflstulans, 397 Aristolen-2-one, 240, 24 1 Artemesia annua, 212 Artemisinin, 2 12 Artifacts, 292,293,355, 356 Assays, 5-7

overlay, 7,240-243 Asterolasia drummondii, 235, 236 Asterolasia trymalioides, 235 Avermectins, 442-444 B Bacillus cereus, 47 Baljet reagent, 357 Base deactivation, 184, 404 Batzelladines, 385-387 Beauveria nivea, 101, 102, 106, 107,

441 Benzoanthracenes, 204,205 Benzopyrenes, 204,205 Berberis sp., 236 Bial’s reagent, 222 Bioassays, 5-7,233-243 Bioautography,

direct, 239, 240 overlay, 240-243, 379

Bio-Gel, 33 1, 334 Biosynthesis, 43 l-445

blocked, 43 l-434 directed, 434-445 enzyme inhibitors, 433, 434 halogenation, 444, 445 mutasynthesis, 434,435

Biotransformation, 445-456 feeding conditions, 449,450 general methods, 44H5 1 medium, 450,45 1 organisms for, 447,448

Bonded phase silica, 115-l 17, 168- 170

Boronia coerulescens, 236

465

466 Index

Boronta wconspicua, 236 Chloromonicilm, 445 Boronia inornata, 234 Chloropinselin, 445 Borntrager’s reagent, 22 1 Chromatography, general 14-40 Broadening, peak, 195 classification, 15-2 1 Brunswgia josephinae, 236 column efficiency 24,25, 36, 37 C detection, 21 Calea divaricata, 234 dispersion, 25, 26 Calystegine, 238 identification by, 30, 31 Capacity factor, 23, 34 improving separations by, 34-40 Capsanthin, 275 integratron, 32, 33 Carbapenam carboxylic acids, 19 1, low-pressure column

192 chromatography, 11 l-140 Carbapenem carboxyhc acids, 19 1, 192 stationary phases, 114-l 2 1 Carbohydrates, detection of, 358 selecting condmons, 122-l 24 Carmmomycin, 455 open-column chromatography, see Cartridge columns, 153, 154,201 Low-pressure column Casearia tremula, 234 chromatography Castanospermine, 238 particle size, 37, 38 Castanospermum au&rule, 238 principles of, 2 l-30 Castllleja rhexifoha, 235 resolution, 28-30 Catalpol, 235 selectivity, 27, 28, 38-40 Cation exchangers, 147 solvent selection, 34, 35 CCC, see Countercurrent Clnachyra, 395

chromatography Cmeromycm B, 237 Cellex, 148-l 5 1 Cispentacin, 42, 47 Centrifugal partition chromatography, Citrus decumana, 237

see Countercurrent Clarification of broths, 54 chromatography Clerodane diterpenes, 230

Cephalochromm, 173, 174, 185-l 87, Coil planet centrifuge, 248-250, 253, 195-197 254

Cephalomannine, 255,256 Combmatortal btosynthesrs, 3 18-320, Cephalosporm C, 59,78-80 456-458 Cephamycms, 159, 160 Common nonselective bioactlve Centrifugal TLC, 229-23 1 natural products, 285-292, 353- Centrifugation, 54, 55 355,382-385

settling velocity 55 Cotoneaster acutifolius, 235 Charge, 9, 10 Cotonefuran, 235 Chemical detection methods, 2 19- Countercurrent chromatography, 247-

222,284-292,356-358,426 259 Chelex, 335 applications, 250-252, 254-257 Chiral separations, 203-205 instruments, 248-250

Index 467

method development, 252,253 CPC, see Countercurrent

chromatography CPTLC, see Centrifugal TLC Crambescidins, 385-387 Critical point, 9 1, 92 Crossflow tiltratlon, 57-59 Croton cuneatus, 299,300 Cystodites, 391 Crystallization, 265-278

common problems, 270,271 obtaining crystals, 266271 selecting a crystal, 27 l-273 as separation method, 273-276

Cucurbitacms, 304,305 Cupresol, 234 Cupressus goveniana, 234 Cyclosporin/e, 101, 102, 106, 107,

441,442 Cytochalasins, 454,455 D Databases of natural products, 309--

312,344,345 Daunomycm, 454-456 Dead-ended filtration, 56, 57 2, 3-Dehydrocephalochromm, 185-

187,195-197 13-Demethylisodysidenin, 400,401 Dercitins, 39 l-393 Dercitus, 3 9 1 Dereplicatton, 279-327

bioassay methods, 303-309 confidence levels, 3 13-3 15 computational methods, 301-303 mass spectrometry, 294299 separation methods, 28 l-284 spectroscopic methods, 293-301

Desalting and sample concentration, 137, 192,200,201,262,263

Detergent-like natural products, 285, 286

Diaion, 148-15 1 Diammopimehc acid, 2 15 Diatomaceous earths, 56,57 2-(2’,4’-Dibromophenyl)-4,6-

drbromophenol, 400,40 1 Dihydrogranatirhodin, 3 19 Dihydrorugosmone, 236 2,9-Dihydroxyaphyllidine, 139, 140 2,8-Dimethyl-1,7-

dioxaspiro[5.5]undecane, 204, 205

Dipetalolactone, 235 Diode array detection, 173 Displacement, 195-l 98 Distribution coefficient, 15, 19, 60, 6 1 Domoic acid, 339, 340 Doramectin, 443,444 Dowex, 145, 148-151 Dragendorff s reagent, 22 1, 356 Dragmacidin, 366 Droplet countercurrent

chromatography, 248 Drying, 263-265 Drummondita hassellii, 235 Duolrte, 148-15 1 Dysldea herbacea, 399,400

E Ectemasctdm, 397, 398 Ehrlich reagent, 222 Elaiophylin, 283, 284 Eluotropic series, 35, 36 Endcappmg, see Base deactivation Epipentenomycin, 42,46 Eriostemon gardneri, 236 Eriostemon myoporoides, 235,236 Expanded bed adsorptlon, 74-84

adsorbents for, 77-8 1 methods, 8 l-84

Extraction, see Isolatron F Fatty acids, 290, 353

468

Fermentation development, 411417, 430,43 1

experimental design, 4 14-4 16 medium development, 413,414 optimization of fermenter

conditions, 4 16,417 scale-up, 4 1 l-41 3 seed stage development, 417 titer improvement, 4131117 transfer to liquid medium, 4 11

Filter aids, 56 Filtration, 56-59 Flash chromatography, 128-l 30 Flavonoids, detection of, 357 Follow-up of isolation, 425-463

complete isolation, 427-430 further isolation, 425-430

Forestine, 237 Fractionation, 4, 5 Friedelanes, 223, 224 Fronting peak, 27 Frullanolides, 454 Fusarwm sporotrichioides, 433

G 2-O-Galloylpunicallin, 137, 138 Gel filtration, 18, 19 Gel permeation chromatography, 18,

19 Geldanomycin, 283, 284 Gene expression, 430,43 1 GLC (gas liquid chromatography), 15 Glucopiericidinols, 42,44 Gonystylus keithii, 304 Gradient elution, 35, 36, 176, 177 Graminone B, 235 Granaticin, 3 18, 3 19 Grease, see Artifacts Gualamycin, 162 Guard columns, 193 H

Index

Halitoxin, 382, 383 Heat stability, 10 Herbadysidolide, 400,40 1 High-performance liquid

chromatography, see HPLC High-speed countercurrent

chromatography, see Countercurrent chromatography

Hippamme, 237 Homalium langifolium, 236 HP20, see also Dialon, 120, 192,42 1 HPLC, 165-208,421,422

buffers, 178, 179 column selection, 175, 176 equipment, 17 l-1 75 fraction collection and work-up,

199-201 isomer separation,

enantiomers, 203-205 positional isomers, 203,204

method development, 175-188 normal phase, 168,203,204 pH effects, 179-l 83 recycling HPLC, 198, 199 scale-up, 193-l 99 separation modes, 166-l 7 1 stationary and mobile phases, 167-

171 strongly retained materials, 202,203

HSCC, see Countercurrent chromatography

Hydrophobic resins, 120, 121,421 Hydrophobicity/hydrophilicity, 9 2-Hydroxyaphyllidine, 139, 140 Hydroxyeutapolide-8-O-angellate,

234 7’-Hydroxyseiridin, 236 Hyrtios alturn, 395

I

Immunomycin, 76, 135, 136 Halistanol sulfate, 382, 383 Imperata cylindrica, 235

Index 469

‘Interfering’ natural products, see Common nonselective bioactive natural products

Ion-exchange chromatography, 18, 141-164

applications, 158-l 63 materials, 144-146 methods, 147-158 resin cycle, 155 resin preparation, 154, 155 resin selection, 147-154 theory, 142-l 44

Ion-pairing/Ion suppression, 18, 177- 182, 190-192

Ipsdienol, 204,205 Isocratic elution, 176, 177 Isolation,

aims of, 2, 3, 5 general strategy, 40, 41 starting, 8-l 4

J

Jaspamide, 308,309 K

Kn, see Distribution coefficient Kedde reagent, 357 Kuanoniamines, 391-393 L

Lactones, detection of, 357 LC-IR, 301 Legal reagent, 357 LC-NMR, 299-30 1 Leonitis ocymifolia, 234 Liebermann-Buchard test, 358 Literature 11, 12, 309-312 Liquid-liquid extraction, see Solvent

extraction LH-20, 119, 120, 134, 135, 137,

138 Localization of compound being

isolated, 11

Low-pressure column chromatography, 11 l-140

Lupinus argentus, 139, 140

M

Macroreticular resins, 144, 145 Maculosidine, 236 Marine natural products, 365-408

collection and storage of organisms, 370-375

initial extraction methods, 375-377 invertebrates, 375, 376 macro algae, 376

localization of metabohtes, 397- 401

method development, 377-379 microbial production of, 396-401 review of literature, 366-369 water-soluble compounds, 38 1, 382

Mayer reagent, 356 Medium pressure liquid

chromatography, see MPLC Milbemycms, 456, 457 Mitomycins, 441,442 Monilinia fructicola, 445 Mobile phase, 14, 15 Molisch reagent, 358 Morus alba, 238 MPLC, 130-132,421,422

N Nardoa tuberculata, 384 Naringin, 274 Nectria episphaeria, 173, 184-l 87,

195-197 Neoisostegane, 235 Nature of compound being isolated,

8-11 Niddamycms, 255,256 Ninhydrin, 22 1 Nitrocefin, 290,291 Nocardia, 43

470 Index

Normal phase, 17, 168 Nuisance compounds, see Common

nonselective bioactrve natural products

Numbers of natural products identified, 3 12,3 13

0 Okadaic acid, 400, 402 Oscillatoria spongeliae, 400 Odyendyea gabonensis, 23 1 OPTLC, see Over-pressure TLC Overlay assays, see TLC, bioassays Overload, column, 195 Over-pressure TLC, 23 1,232 Oxidation/reduction mhrbrtors, 287-

289 P Packing columns, 124-126

dry packing, 125, 126 slurry packing, 125

Palau’amine, 16 1, 162 Panosialins, 290 Papaver somniferum, 236 Paromomycms, 162, 163 Parthenollde, 105, 106 Partisil 40, 192 Partition chromatography, 16, 17,

113,114 PartWon coefficients, see Distrlbutron

coefficient Paxilline, 307, 308 Penicillins, 64, 65 Penicillium paxilli, 307 Penicillium sclerotium, 237 PeptideP95 1, 398-400 Perlites, 56, 57 Pezlza, 46 Phase capacity factor, see Capacity

factor Phase-transfer catalysts, 190 Phenazine- 1 -carboxyhc acid, 179-l 83

Phoma sp., 427 Phyllobotryon spathulatum, 223,224 Phytoecdysteroids, 198, 199 Picea abies, 238 Pigments, 354 Piperine, 274 pKa, 9,146,147 Plackett and Burman experimental

design, 4 15 Planar chromatography, 209-246 Plants, 343-363

collection and identification, 344, 345

drying and grinding, 345, 346 general methods of detectron, 356

358 general methods of extractron,

348-353 initial extraction, 346-356

aqueous, 35 1 maceration, 350, 35 1 percolation, 349, 350 solvents, 347-349 Soxhlet extraction, 35 1

Plasticizers, see Artifacts Plate number, see theoretical plate

number PLC, see Planar chromatography Pneumocandins, 76, 137-139 Polyacridines, 387-393 Polyacrylamlde, 117 Polyamines, 383,384 Polyenes, 308 Polyphenols, see also Tannins, 285,

287,288,357 Polystyrene stationary phases, 120,

121, 136, 137, 145 Pradimicins, 43 1,432 Preparattve TLC, 223-239 Pristinamycins, 254, 255 Product capture, 53-89

Index 471

Prostanthera spp., 240 Prostantherol, 240,241 Pseudomonas aureofaciens, 443,444 Pseudomonas aeruginosa, 179-l 82 Pseudonitzschia pungens, 339, 340 Psilocybe mexicana, 2 12 Psilocybin, 2 12 Ptilocaulins, 387 Ptilomycalins, 385-387 PTLC, see Preparative TLC Purity, 3,4, 261,262 Pyocyanme, 179-183 Pyrrolnitrin, 443,444

Q Quantification, 7, 8 Quassinoids, 23 1, 232 Quinolizidines, 139, 140 R R, 210 Rachelmycin, 137-l 39 Refractive index, 175 Retention, 22-24 Reverse phase 17, 168-170 S Saframycin, 397, 398 Salicin, 275 Salkowski reaction, 358 Saponins, 42,45,290,291,352,353,

358,384 Scale-up, 409

downstream process development, 419-422

preliminary data, 4 I9 effect on downstream processing,

417-419 extracellular products, 420,42 1 intracellular products, 4 19,420 purification, 42 1

Secondary metabolism, 1,2 Seiridium sp., 235

Senna multiglandulosa, 237 Sepabeads, 42 1 Sephadex, 118-120, 146,148-l 5 1,

33 1,334,335 Serjania salzmanniana, 42,44 Serratia marcescens, 190-l 92 Sesquicillium sp., 188, 189 SFE, see Supercritical fluid extraction Shermilamine, 392 Shinoda test, 357 Silanes, 116 Silanols, 115, 116, 182-l 84 Silica, 115-l 17, 146 Silica column chromatography,

general methods, 133, 134 Size exclusion chromatography, 18,

19,113, 134,135, 170 Size of natural product, 10, 11 Solanine, 274 Solid-liquid separation, 54-59

solid-liquid density differences, 55 Solid phase extraction, 12, 13,68-74,

378 as dereplication tool, 282,283

Solvent extraction, 59-68 of antibiotics, 62 equipment, 62-64 methods and examples, 64-68 solvent selection, 61, 62, 68

Solvent properties, 63, 169 Solvent strength, 34,35,212 Solvent selectivity triangle, 38, 39 Sorangium cellulosum, 48 Soraphens, 42,48 Sorption isotherms, 26,27 SP200, 120 Spathulenol, 234 Spectral libraries, 173-l 75,294 Spirastrella spinispirulifera, 395 Spirocardins, 41-43 Spongia sp., 394

472 index

Spongrstatins, 393-396 Spongosorites, 365 Squalestatms, see also Zaragozic

acids, 427430,437-440,45 l- 453

Stationary phase, 15 Steganotaenta arahacea, 235 Sternbergia lutea, 237 Sterols, detection of, 358 Streptomyces avermitilis, 442 Streptomyces caeapitosus, 44 1 Streptomyces djarkartenszs, 255 Streptomyces fradtae, 44 1 Streptomyces galileus, 432 Streptomyces griseoviridis, 237 Streptomyces pristinaespiralts, 254 Streptomyces violaceusniger, 282-284 Styrene divinylbenzene, 120, 12 1,

171,421 Sulfate ester-containing compounds,

382-385 Supercritical fluid extraction, 91-109

applications, 103 method development, 10 l-l 03 sample collection, 97, 98 sample preparatron, 96 solubtlity of solids in supercritical

fluids, 92-94 systems for, 94-98

Swmholide, 398, 399

T Tailing, peak, 27, 184 Tannins, 201,202,285,287,288,

291,292,354,355 Taricha granulosa, 336,337 Taxol, 106,215,255,256,298,299,

307,308

Teichaxinella morchella, 382 Teicoplanins, 454 Terminalia chebula, 136 Tetracenomycin, 3 18, 3 19 Tetrodotoxins, 336-339 Thalictrum faberi, 237 Thalifaberme, 237 Theonella swinhoei, 398,399 Theoretical plate number, 24 Thin layer chromatography, see TLC Tinuvin 770,292,293 TLC, 209-246

AMD, see Development, forms of, applications, 2 14-2 16, 233-239 bioassays, 233-243 centrifugal TLC, 229-23 1 detection, 217-222,226,227

stains/spray, 2 19-222 uv, 219

development, forms of, 2 17 tomated multiple development,

232 general systems, 2 18 modes of separation, 2 1 l-2 14 preparative plates, 224-226 princrples, 2 10,2 11 recovery of products from, 227,

228 sample application, 226 scale-up, 223,224 two-dimensional, 232,233

Tocopherols, 203,204 Topsentin, 365, 366 Toxic natural products, 285,286 Tricontanol, 292,293 Tricothecenes, 433 TSK gels, 148-151

Taxomyces andreanae, 2 15 U Taxus baccata, 298 UV quenching natural products, 288, Taxus brevtyolia, 2 15, 298, 307 289

Index 473

Uvaria angolense, 237 Uvarindole, 237 V Vacuum liquid chromatography, 129,

130 van Deemter equation, 26 Vitexirone, 198, 199 VLC, see Vacuum liquid

chromatography w Wagner reagent, 356 Water-soluble natural products, 329-

342

buffers for, 330-332 desalting, 330,33 1 general methods, 329-335 heavy metal problems, 333-336

X XAD, see also Amberlite, 120, 192 Z Zalerion arboricola, 76 Zaluzania grayana, 301,302 Zaragozic acids, see also

Squalestatins, 160, 161, 3 11, 312

Zuelania guzdonza, 230, 23 1