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METHODS IN MOLECULAR BIOLOGY™ Series Editor John M Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 Natural Products Isolation Third Edition Edited by Satyajit D Sarker Department of Pharmacy, School of Applied Sciences, University of Wolverhampton, Wolverhampton, UK Lutfun Nahar Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, UK Editors Satyajit D Sarker, Ph.D Department of Pharmacy School of Applied Sciences University of Wolverhampton Wolverhampton, UK Lutfun Nahar, Ph.D Leicester School of Pharmacy De Montfort University Leicester, UK ISSN 1064-3745 e-ISSN 1940-6029 ISBN 978-1-61779-623-4 e-ISBN 978-1-61779-624-1 DOI 10.1007/978-1-61779-624-1 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2012932311 © Springer Science+Business Media, LLC 2012 All rights reserved This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com) Dedication Dedicated to the memories of our dads Preface The use of natural products for the treatment of various ailments can be traced back thousands of years, and many “block-buster” drugs that we use today have come from natural origins Because of unique inherent chemical diversity, natural products have continued to be one of the major sources of new drug molecules still today In recent years, there has been a remarkable resurgence of interests observed in the area of natural products research With significant developments in the areas of chromatography and spectroscopy, natural products research has gained new momentum Natural products and their analogs are now suitable for high-throughput screening, and have become part of major and meaningful drug discovery programs Isolation of natural products is one of the main components in natural products research, especially in relation to drug discovery and development Techniques for extraction and isolation of natural products from various matrices have evolved over the years, and particularly, over the last couple of decades, the advances in extraction and isolation technologies have made isolation of natural products less laborious and less time-consuming The last two editions of this book captured most of the techniques that are generally used in natural products extraction and isolation Since the publication of the second edition in 2005, there has been significant progress in these areas, which certainly demands the publication of this third edition to document new methods and technologies for natural products isolation This thoroughly revised third edition has incorporated a total of 20 chapters; some are new chapters, while some others are expanded or updated version of the chapters from the second edition, using a slightly new lay-out and style Chapters in this edition have included a number of “hands on” approaches and “step-by-step” protocols to help natural products researchers follow and implement these protocols in their own research Like the previous editions, it is still our intention to provide substantial background information for budding natural product researchers as well as to offer reference guide to available methodologies and techniques for the more experienced researchers Wolverhampton, UK Leicester, UK Satyajit D Sarker Lutfun Nahar vii Contents Dedication Preface Contributors v vii xi An Introduction to Natural Products Isolation Satyajit D Sarker and Lutfun Nahar Initial and Bulk Extraction of Natural Products Isolation Véronique Seidel Supercritical Fluid Extraction in Natural Products Analyses Lutfun Nahar and Satyajit D Sarker Accelerated Solvent Extraction for Natural Products Isolation Mohammad A Mottaleb and Satyajit D Sarker Microwave-Assisted Extraction in Natural Products Isolation Abbas Delazar, Lutfun Nahar, Sanaz Hamedeyazdan, and Satyajit D Sarker An Introduction to Planar Chromatography and Its Application to Natural Products Isolation Simon Gibbons Isolation of Natural Products by Low-Pressure Column Chromatography Raymond G Reid and Satyajit D Sarker Isolation of Natural Products by Ion-Exchange Methods Klaus Dragull and John J Beck Separation of Natural Products by Countercurrent Chromatography James B McAlpine, J Brent Friesen, and Guido F Pauli 10 Isolation of Natural Products by Preparative High Performance Liquid Chromatography (Prep-HPLC) Zahid Latif and Satyajit D Sarker 11 Isolation of Natural Products by Preparative Gas Chromatography Temel Özek and Fatih Demirci 12 Hyphenated Techniques and Their Applications in Natural Products Analysis Satyajit D Sarker and Lutfun Nahar 13 Extraction of Plant Secondary Metabolites William P Jones and A Douglas Kinghorn 14 Isolation of Marine Natural Products Wael E Houssen and Marcel Jaspars ix 27 43 75 89 117 155 189 221 255 275 301 341 367 NATURAL PRODUCTS ISOLATION 538 Index Chinese danggui 83 traditional medicine 3, 232, 241, 330, 331 Chiral center 18, 361, 488 Chloramphenicol 151 Chlorofluorocarbons (CFCs) 50, 71 Chloroform (CHCl3) 7, 9, 10, 16, 30, 36, 54, 67, 68, 83, 120, 122, 125, 127, 128, 131, 135, 140, 142–147, 166, 177, 179, 208, 228–231, 236, 239, 257, 261, 273, 334, 348, 349, 354, 357, 359, 361, 410, 411, 420–422, 437, 454, 526 Chlorogalum pomeridianum 416 Chlorogenic acid 106, 111, 428, 448 Chloromonilicin 487, 488 Chlorophyll 63, 122, 134, 165, 183, 354 4-Chloropinselin 487, 488 Chloroquine diphosphate 23 ChMWat 227, 229–230, 232 Chromatotron 11, 124, 137, 138, 421 Chromophore 18, 128, 131, 206, 238, 264, 265, 306, 320, 325, 336, 370–371, 385, 417, 424 Chrysogenin 398 Chrysopogon zizanioides 57 Circular centrifugal chromatography Citrus C reticulata 106 C sinensis 61 C tangerina 324 Cladosporium cucumerinum 148–150 Clematis mansuriea 416 Clethraceae 416 Clethra occidentalis 416 Clevenger apparatus 99 Clitocybe sinopica 181 Closed system 94, 95, 104, 236, 347 vessel 35, 92, 94–96, 104, 105, 109, 111, 420, 425, 441 13 C NMR DEPT 18 J-mod 18 PENDANT 18 Cocaine 109 Codon 382 Coffee .46, 55, 56, 345, 444 Collection of marine samples 372 Column chromatography (CC) development 168, 170–173 equilibration 175–177 injector 277–279 operation 166–183, 205–215 oven 279, 315 packing 168–170, 277 preparation 174–177 selection 284 size 205, 213, 273, 277, 293 switching technique 282 Combinatorial biosynthesis of plant medicinal polyketides 506 Combinatorial synthesis 474, 507–508 Compositae 416 Conocandin 400 Continuous flow 47, 51, 67, 69, 308–311 Cooled injection system (CIS) 284 Copaifera glycycarpa 241 Corydalis cell cultures 318 Corynebacterium aquaticum 498 Co-solvent 45, 48–50, 53, 55, 60–63, 68–71, 213, 214, 448, 449 o-Coumaric acid 103, 104 Coumarin 2, 18, 38, 103–105, 126, 127, 140, 145, 180, 181, 306, 320–321, 428, 441 Counter-current chromatography (CCC) 7, 130, 136, 221–250, 372, 396–397, 399–401, 423, 424, 431, 449, 452–455 Counter-current distribution (CCD) 234, 399–400 Counterion 190–192, 197, 200, 201, 203, 204, 213 CPTLC See Centrifugal preparative thin-layer chromatography (CPTLC) Crinamidine 235 Crinine 235 Crinum moorei 234, 235 Critical point 44, 45, 50, 277, 282, 289, 377, 442 pressure 44, 45, 50 Cryptic species 368 Cryptocarya massoy 241 Cryptococcus 148 Crystal structure 18 Culturing of piezophiles 375 Cunninghemella C echinulata 475, 493 C elegans 475, 498 Curcumin 506 Curvularia lunata 498 Cuscuta reflexa 180–181 Cyanidin glycosides 271 3-O-glucoside 271 3-O-(2G-xylosyl)-rutinoside 271 3-O-rutinoside 271 3-O-sambubioside 271 Cyanobacterium 369 Cyanopropyl 82, 162, 163 Cyanosafracin B 521 Cyclohexane 50, 120, 128, 146, 228, 231, 242 Cyclosporine 65–66 Cytotoxicity 5, 138, 151, 362, 518, 524, 525 NATURAL PRODUCTS ISOLATION 539 Index D Daidzin 103 β-Damascenone 99 Daphneticin 320 Daphnetin, 8-O-β-D-glucopyranoside 320 Daphnin 320 Daphnoretin 320 Datura stramonium 317, 318 Daunomycin 490, 492 Daunomycinone 490 DCCC See Droplet counter-current chromatography (DCCC) Deacylbellidioside B3 421 B4 421 Decoction 353 Defatting 11, 217, 349, 354, 384, 418 Degaser 263 6,7-Dehydroapoatropine 317 Dehydroepiandrosterone 496, 497 6,7-Dehydro-3-tigloyloxytropane 317 5’-Demethoxydaphneticin 320 Demethyl-benzoyl-pyrrothine 484 N-Demethylpuqietinone 318 Depressurization 54, 85 Dereplication 314, 326–329, 355, 358, 378, 383, 386, 396, 406, 476, 523, 526, 529, 532 Desalting 164, 205, 208, 215, 262, 270, 384, 385 DESI (Desorption Electrospray Ionization) mass spectrometry 530 Desolvation technology 307 Detection chamber 304 of natural products 129–130 technology 301 Detector 14, 95, 173, 206, 238, 260, 272, 281–282, 303, 370, 397, 423, 466, 474, 518 Deuterated solvent 306, 311, 314, 316, 327, 409 Dextran gel 122 D-Galactose (Gal) 416 D-Galactronic acid (GalA) 416 D-Glucoronic acid (GlucA) 416 D-Glucose (Gluc) 416, 450, 510 Diadinoxanthin 319, 320 Diatomaceous earth 52, 64, 78, 79, 83, 442 Diatoxanthin 319, 320 Dichloromethane (DCM) 7, 9, 10, 13, 14, 30, 35, 36, 79, 80, 82, 85, 120, 132, 160, 166, 170, 177, 178, 227, 228, 231, 258, 272, 273, 344, 361, 377, 410, 440, 452, 485, 498 The Dictionary of Natural Products 128 Dictyopteris membranacea 99 Dielectric constant 91, 109, 120, 271, 439–441, 443 Diethyl ether 36, 105, 120, 127, 128, 227, 228, 236, 258, 271, 344, 351, 418, 435, 436 Diffuse reflectance infrared Fourier transform (DRIFT) 307 Diffusion ordered spectroscopy (DOSY ) 526, 527, 529 Dihydroandrostenedione 111 13-Dihydrodaunomycin 490, 492 13-Dihydrodaunomycinone 490 Dihydrogranaticin 504 Dihydrogranatirhodin 504, 505 Dihydrokaempferol glycosides 222 Dihydrotestosterone 111 5,8-Dihydroxycoumarin 104 5,7-Dihydroxy-2-isopropylchromon 181, 182 1,3-Dihydroxy-5-methoxyxanthone 181, 182 3,7-Dihydroxy-6-(2’-methylbutyryloxy)-tropane 317 13β,29-Dihydroxymilbemycin A4 493 13β,30-Dihydroxymilbemycin A4 493 26,30-Dihydroxymilbemycin A4 493 3,7-Dihydroxy-6-propionyloxytropane 317 Dimethylformamide (DMF) 165, 370 Dimethyl-secologanoside 325 Dimethylsulfoxide (DMSO) 8, 22, 165, 387, 525 Dioctylphthalate ester 362 Diol 13, 162, 163, 171, 200, 212, 258 Dionex 31, 39, 75, 77, 83, 85, 198, 200, 206, 315, 316 Dioscorea floribunda Dioscorides 3, 396 Diosgenin 2,2-Diphenyl-1-picrylhydrazyl (DPPH) 19, 20, 24, 141 Dipolar rotation 90 Dipole dipole interaction 157 rotation 90 Directed biosynthesis approach 474, 484 Dispersing 77–79, 279, 442 Dissolved oxygen (DO) probe 467–468 Distribution constant 156, 243 Diterpene 63, 64, 123, 125, 138, 142, 151, 180, 231, 239, 241, 242, 502 Dolabella auricularia 369, 520–521 Dolastatin 10 369, 370, 520, 522 13-epi-Dorrigocin A 479 Dorrigocins A and B 479 DOSY See Diffusion ordered spectroscopy (DOSY ) Downstream processing (DSP) 466, 469–470 DPPH See 2,2-Diphenyl-1-picrylhydrazyl (DPPH) Dragendorff ’s reagent 19, 125, 130, 211, 355, 363, 381 DRIFT See Diffuse reflectance infrared Fourier transform (DRIFT) Droplet counter-current chromatography (DCCC) 7, 222, 224, 226, 400–401, 431, 453 Drosophila melanogaster BII cell line assay 19–20 NATURAL PRODUCTS ISOLATION 540 Index Drying 1, 9, 10, 31–32, 35, 38, 52, 65, 77, 79, 130, 134, 135, 262, 270, 318, 319, 321, 324, 326, 328, 344, 345, 359–361, 374, 418, 420, 431–434, 436, 437, 442, 443, 453 Dry packing 169 DSP See Downstream processing (DSP) Dyeing reagents 129 Dynamic microwave-assisted extraction (DMAE) system 101, 102 E Ebeiedine 318 Ebeiedinone 318 Ebeienine 318 ECD See Electron capture detector (ECD) Ecdysone 321, 322 Ecdysteroid 13, 321–323, 336 Eco-friendly 43 Ecteinascidia turbinata 521 Edgeworin 320 Edgeworthin 320 EECCC See Elution extrusion CCC (EECCC) Effective capacity 194 EI See Electron impact ionization (EI) Elatoside E 422 Electric field 90, 111, 312 Electromagnetic field 305 radiation 89, 264, 439 waves of frequency 89 Electron capture detector (ECD) .282, 286, 287 Electron impact ionization (EI) 305, 317, 324 Electrophoretic migration 111 Electrospray 319, 362 Ellagic acid 440 ELSDs See Evaporative light scattering detectors (ELSDs) Elution extrusion CCC (EECCC) 234, 238 EMWat 233 Endophytes .29–30, 37, 40 Endotoxin 370 Enramycin A 231, 242–243 B 231, 242–243 Environmentally friendly 43, 66, 90, 449 Enzyme inhibitors 474, 479, 509 Ephedraceae 331 Ephedra sinica 330, 331 Ephedrine 317, 331, 332 Epicatechin 60, 69, 207, 441, 447, 449 gallate 60, 207, 447 Epigallocatechin 207, 447 gallate 207, 447 Epilobium 332 Eremostachys glabra 180 Erica arborea 180 Erythromycin A 506, 511 Erythroxylum coca 109 Escherichia coli 486, 506 Escin IA 83, 84 IB 83, 84 ESI-MS 239, 312, 313, 321, 324, 326, 335 Essential oil .34, 38, 56–58, 63, 90, 99–101, 112, 285, 294, 317, 320, 324, 502 polyunsaturated fatty acids 72 17β Estradiol 111 Estrone 111 Ethanol (EtOH) 7, 9, 10, 30, 36, 37, 50, 57, 58, 60–62, 64–66, 68–70, 82, 85, 91, 97, 101, 103, 104, 107, 110, 111, 125, 143, 178, 181, 209, 210, 213, 228, 256, 322, 323, 331, 350, 352, 356, 357, 360, 361, 374–377, 394, 417–424, 432, 436, 440, 443, 448, 449, 483, 495, 502 Ethnobotanical sources 343 Ethyl acetate (EtOAc) 7, 30, 79, 105, 120, 160, 206, 227, 258, 344, 404, 418, 432, 471, 491, 526 Ethylene glycol 165, 370 7-O-Ethyl-sweroside 325 EtOH See Ethanol (EtOH) Eucalyptus perriniana 502 Eucommia ulmodies 106 Eudistoma toealensis 521 Eugenol 502 Euphorbia petiolata 272 Evaporative light scattering detectors (ELSDs) 206, 238, 264, 371, 385–387, 417, 423, 424 Extraction of carboxylic acids 352 cells .52, 53, 83, 85, 95 conditions 40, 58, 61, 69–71, 82, 84, 85, 99, 101, 103, 106, 107, 109, 111, 350, 418, 437 container 95, 376 cycle 85, 438 efficiency 58, 61, 65, 68–70, 75, 79, 85, 90, 98, 102–104, 106–110, 112, 419, 438, 440, 442, 443 equipment 96, 345–346 kinetics 75 of marine natural products 376–378 method 8, 9, 28, 60, 62, 69, 86, 90, 97, 101–104, 110, 348, 353, 354, 360, 383, 403, 419, 420, 431, 438, 443, 446 parameters 68, 79–81, 98, 100, 110 of phenolic compounds .436, 438–440, 447, 448 rate 60, 90, 419, 439 recoveries 83, 92, 448 under reflux 28, 32, 34 NATURAL PRODUCTS ISOLATION 541 Index of saponins 83, 109–110, 417–424 selectivity 45, 46 solvent .10, 11, 19, 28, 32–34, 39, 46, 50, 62, 63, 69, 75–86, 90, 94–98, 100–102, 105–107, 109–111, 346, 360, 397, 418, 420, 431, 432, 434, 436–441, 443, 449, 470, 482 technique .9, 75–77, 82, 90, 92, 97, 101, 103, 346, 436, 438–440, 442 technology 90, 346 time .55, 58–60, 62, 65, 67, 71, 81, 83, 85, 90, 91, 98–100, 102, 103, 105, 106, 109–111, 419, 437–439, 444, 446, 449 vessel 47, 51–53, 56, 62, 63, 70, 71, 92, 94–96, 102, 104, 105, 109, 441, 443 yield 39, 57–62, 69, 91, 97, 98, 102–104, 110, 438, 443 F Fabaceae 416 FAB interface 308, 325 Fagus sylvatica 324 Farfantepenaeus paulensis 69, 72 Fermenter 31, 35, 40, 410, 467, 529 Ferric chloride (FeCl3) 19, 37, 40, 354, 355, 357 Ferula hermonis 179–180 Ferulic acid 107, 428 Feverfew 62–63, 329 Ficus vallischoudae 517 FID See Flame ionization detector (FID) Filamentous fungi 66, 490 Filtration 32, 39, 40, 76, 95, 96, 98, 157, 164–166, 168, 178–180, 213, 346, 376, 404, 406, 431, 434, 437, 438, 441, 442, 471, 478, 498, 502, 510 Flame ionization detector (FID) 281, 283, 284, 286, 287, 530 Flame photometric detector (FPD) 282, 286, 287 Flash chromatography (FC) 7, 9, 11, 131, 170–172, 206, 266, 272 Flavonoid 2, 38, 60–62, 101, 125, 167, 223, 272, 306, 353, 428, 506, 526 Fleming, A 398, 411 Florisil 77, 83, 86 Focused microwave-assisted hydrodistillation (FMAHD) 99, 100 system 92, 93 Follow-up of natural products isolation 473–511 Formic acid 80, 129, 205, 206, 239, 262, 271, 309, 321, 323, 452, 484, 485 Formoyl-pyrrothine 484 Fourier-transform infrared (FT-IR) 286, 302, 306, 307, 314, 315, 321, 322 FPD See Flame photometric detector (FPD) Fraction collection 173, 175, 176, 263, 268–270 collector .166, 175, 215, 236, 265, 268, 270, 273, 282, 283, 311, 314, 388, 423 Fractionation of marine extracts 378–386 Fragmentation .18, 37, 304, 307, 335, 363, 386, 493 Fragment ions 304, 307, 320, 324, 325 Free-radical-scavenger 19, 20, 24 Freeze-dry(ing) 29–31, 35, 79, 86, 103, 262, 270, 345, 374, 433, 436, 437, 442 Freon® 71 Friedelane triterpene 131 Fritillaria 318 D-Fucose (Fuc) 416 Fumonisins B1, B2, B4, and B6, 206, 215 Furanocoumarin 104 Furanolabdane diterpenes 180 Furostanol saponins 416 Further extraction 433, 474–478 Fusarium sporotrichioides 504 G Galanthamine 141, 143, 144, 148 Galanthus nivalis 143 Galen 3, 396 Galenical 3, 396 Gallic acid .107, 428, 435, 449 Gallocatechin gallate 447 Ganoderma atrum 109 Gas chromatography (GC) application 275, 278, 282, 290 columns 277, 285, 304, 316, 317 detectors .281–282, 286, 287 instrumentation setup 283–284 separation 276, 277, 290–293 system 277, 282–284, 446 technique 275, 303 Gas chromatography – Fourier transform infrared (GC-FTIR) 317 Gas chromatography mass spectrometry (GC-MS) 57, 70, 80, 85, 100, 111, 301–305, 315, 317, 318, 324, 329–332, 334, 418, 474, 476, 500, 523 Gas-liquid chromatography (GLC) 276, 399 Gas-solid chromatography (GSC) 276 Gastrodia elata 105 Gastrodin 105 GC-FTIR See Gas chromatography – Fourier transform infrared (GC-FTIR) GC-MS See Gas chromatography mass spectrometry (GC-MS) Gel filtration chromatography (GFC) 157 permeation chromatography (GPC) 157, 167, 181–183, 257, 259, 260 NATURAL PRODUCTS ISOLATION 542 Index Generally Useful Estimate of Solvent Systems (GUESS) 227–228, 230, 233, 234, 243, 244 Geniposidic acid 106 Genistein 103, 429, 446, 449, 506 Genistin 103 Genome mining .375, 379, 382 Gentianaceae 333 Gentiana rhodantha 325 Gibberella G fujikuroi 400, 401, 475 G pulicaris 479 Gibberellin 400, 401 Ginkgo leaves 61 powder 61, 70 Ginkgo biloba 61, 69, 454 Ginkgolide 61, 70 Ginsenosides 140, 419, 423, 424 Girard’s hydrazide reagents (H2N··NH·CO·CH2·NR3+Cl-) 351 Glaucarubolone 151 Glucosinolates 433 Glycitin 103 β-Glycosidases 431, 434 Glycoside 2, 11, 38, 127, 128, 135, 140, 144, 147, 217, 222, 223, 232, 270–271, 323–326, 333, 336, 350, 351, 356, 421, 435, 437, 449, 450, 490 Glycyrrhiza G glabra 2, 239 G urulensis 110 Glycyrrhizic acid 110 Gradient analysis 266–267, 269 elution 170, 213, 214, 232, 265, 267, 311, 312, 318, 323, 327, 417, 451, 452, 485, 502 formation 170 scout 267 Gram negative 36 positive 36 GRAS (generally recognized as safe) 443 Gravity-based methods 434 Green chemistry 43 technology 99 Grinding 9, 31–32, 52, 71, 77, 78, 418, 431, 434, 447 Gualamycin 401, 402 Guard column 264, 502 GUESS See Generally Useful Estimate of Solvent Systems (GUESS) Guttiferae 150 H Haematococcus pluvialis 69 Halichondria H melanodocia 520 H okadai 520 Halocarbons 49 Halogenated hydrocarbons 257 Halophyllum acutifolium 328 Harmaline 232, 236 Harmane alkaloid 235, 236 Harmine 232, 236 Helium gas 260 “sparge” system 260 Heme biocrystallization or polymerization assay 20, 22–23 HEMWat 227, 229, 232, 233, 238 Heracleum sphondylium 139 HETCOR 528 Heteronuclear single quantum coherence (HSQC) 18, 526–529 Hexane 109, 120, 127–129, 131, 160, 209, 217, 227, 228, 232, 239, 261, 344, 349–351, 354, 377, 410, 437, 440, 448 Hierochloe odorata 104 Highly non-polar compounds 128, 349 Highly polar metabolites 128 High performance liquid chromatography (HPLC) FT-IR 286, 314 IR 306 MS 80, 307, 325, 329, 333 NMR 309, 310, 312, 314 PDA 11, 305, 314, 320, 323, 325, 328–331, 334–336 PDA-MS-SPE-NMR .314, 328, 329 SPE-NMR 445 High pressure and temperature extraction (HPTE) 442 High-speed CCC (HSCCC) 223, 237, 241, 242, 401, 417, 418, 422, 423, 453 High-throughput sample preparation 90 screening (HTS) 3, 5, 19, 368, 371, 386–388, 517–519, 531 Hippocrates 2, 3, 395 HMBC 18 Homogenization .431, 432, 434 Hops 55, 56 Hormococcus conorum 400 HPLC See High performance liquid chromatography (HPLC) HPTLC See Thin layer chromatography (TLC) HSCCC See High-speed CCC (HSCCC) HSQC See Heteronuclear single quantum coherence (HSQC) HTS See High-throughput screening (HTS) NATURAL PRODUCTS ISOLATION 543 Index Hupeheninoside 318 Hydrocarbon 30, 36, 37, 49, 71, 80, 81, 100, 192, 194, 199, 257, 258, 281, 285, 287, 319, 363 Hydrodistillation 9, 99, 100 Hydrogen-bonding 76, 112, 120, 121, 157, 160, 166, 192, 210, 354, 447, 449 Hydrolysis 38, 56, 99, 351, 404, 417, 418, 431, 432, 434–437, 446, 493, 495 Hydrophilicity 10, 165, 380 Hydrophobic 122, 161, 194, 196, 198, 210, 245, 259, 384, 385, 405, 415, 445, 447, 449, 450 Hydrophobicity 10, 450 3α-Hydroxyartemisinic acid 500, 501 3β-Hydroxyartemisinic acid 500, 501 p-Hydroxybenzoic acid .107, 428, 448 15-Hydroxycadin-4-en-12-oic acid 500, 501 8-Hydroxycanthin-6-one 138 3α-Hydroxydihydroartemisinic acid 500, 501 3β-Hydroxydihydroartemisinic acid 500, 501 20-Hydroxyecdysone 11, 13, 321, 322 Hydroxylated solvents 258 13β-Hydroxymilbemycin A4 493 29-Hydroxymilbemycin A4 493 30-Hydroxymilbemycin A4 493 Hyperforin 62, 63 (-)-Hypericin 328 Hypericum H ascyron 181, 182 H brasiliense 150 H perforatum 62 Hyphenated technique 7, 9, 11, 301–336, 371, 393, 397, 406–407, 418, 474, 476 Hyphenation 301, 302, 307, 313–315, 328 I IEC See Ion-exchange chromatography (IEC) Immunosuppressant 65 Imperatorin 104 Imperialine 3-β-D-glucoside 318 Indole alkaloid 14 Indolizidine alkaloid 211, 216 Indolmycin 205, 215 Inert gas 304 Instability of metabolites 370 Interface 112, 118, 132, 139, 236, 305–312, 318–320, 323–325, 328, 333, 385, 482 Interfering compounds .82, 342, 354–355 In vitro 5, 19, 333, 348, 380, 504, 518, 524, 525 In vivo 5, 19, 256, 348, 349, 380, 398, 482, 504, 507, 524, 525 Ion exchange resins 77, 164, 171, 192, 445, 510 source 304, 305, 317, 321, 334 suppression 262 trap mass spectrometer .311, 313, 324, 327 Ion-exchange chromatography (IEC) 189–191, 194–199, 202, 205–209, 211, 214–218, 372 Ionic conduction 90, 111 liquid 107, 108, 112, 440, 441 Iridoid 2, 125, 306, 325–326, 333, 336 Isocratic condition 264, 267–268 elution 13, 267, 371 system 138, 267 Isoescin IA and IB 83, 84 Isoflavone 103, 147, 324, 429, 446, 449, 450 Isoflavonoid 101–103, 306, 323–324, 454, 506 Isofraxidin 104 Isolation of crude saponins 350–351 of marine microorganisms 375 of marine natural products 367–390 of microbial natural products 12, 393–411 of penicillin 396–400, 411 of phenolic compounds 180, 427–455 of piezophilic marine microorganisms 375–376 of saponins 415–425 of therapeutic penicillin 397–399 Isoliensinine 236 Isomigrastatin 479 Isoprene units 480 Isopropanol .30, 258, 361, 390 Isoverticine 318 Ito coil planet centrifuge 237–238 J Japanese danggui 83 Japanese knotweed 65 K Kaempferol 3-O-(2-galloyl)-glucoside 272 3-O-glucoside 272 3-O-rhamnoside 272 Kaurenoic acid 241 KBr 307, 511 KCl 307, 511 Kedde reagent 356 Ketolides 506–507 Kieselgel 119, 124, 132, 137, 148 KOH 126, 132, 356, 362, 435 Korean danggui 83 NATURAL PRODUCTS ISOLATION 544 Index L β-Lactam, antibiotics 402 Lamiacea 149, 151 L-Arabinose 416 Large volume injection (LVI) 299, 303 LC See Liquid chromatography Legal reagent 356 Leguminosae 317 Lentibulariaceae 333 Leptodontidium 477 Licorice 2, 110, 239 Liebermann-Burchard reagent 16, 357, 421, 425 Liensinine 231, 232, 236 Limnantheoside A 11, 13 B 13 Limnanthes douglasii 11–14 d-Limonene 498–500, 502 Limonin glucosides 217 Lipophilic compounds 38, 257, 374 Liquid chromatography Fourier transform infrared (LC-FTIR) 301, 315, 316 infrared spectroscopy (LC-IR) 306, 307, 316 mass spectroscopy (LC-MS) 316, 354, 355, 385, 386, 493 mass spectroscopy - mass spectroscopy (LC-MS-MS) 385, 386 nuclear magnetic resonance (LC-NMR) 316, 385, 386, 526 nuclear magnetic resonance - mass spectroscopy (LC-NMR-MS) .316, 385, 386 photo-diode-array (LC-PDA) 315 photo-diode-array mass spectroscopy (LC-PDA-MS) 302, 314, 321, 323, 327, 333, 334 photo-diode-array - nuclear magnetic resonance - mass spectroscopy (LC-PDA-NMR-MS) 302, 313, 317 thermal lens spectrometry (LC-TLS) .313, 319, 320 thermospray - mass spectroscopy (LC-TSP-MS) 308 ultraviolet- mass spectroscopy (LC-UV-MS) 308, 311, 327 Liquid-liquid extraction 9, 28, 34, 207, 399, 401, 403, 417, 434 Liquiritin 110 Lirope spicata 181–183 Lisianthius seemannii 325 Listonella damsela 498 Loganin 325 Long chain alkane 257, 273 Lonicera japonica 111 Low-pressure column chromatography (LPLC) 156, 158, 159, 163, 164, 166, 168, 170–174, 178, 181, 417 L-Rhamnose 419 Lutein 72 Luteolin 335, 429, 447 LVI-GC-MS 303 Lychnis flos-coculi 321, 322 M Maceration 9, 14, 28, 32, 33, 35, 38, 178–180, 270, 322, 345–348, 352, 353, 376, 389, 418, 420, 522 Macrobore 305 Magnetic field 90, 310 stirrer 11, 101, 111 Magnetron 92, 106, 108 Mahuang 317 Maillard reaction 442, 455 Makisterone A 321, 322 MALDI (Matrix Assisted Laser Desorption Ionization) 18, 523, 530 Malonylshisonin 334 Malvin acetate 60 cumarate 60 Marine natural products 367–390, 520, 530 Mass analyzer 308 detector 265, 328 selective detector (MSD) 282, 287, 315, 317, 324 spectra 304, 307, 318, 319, 322, 324, 326, 330, 335, 362, 486, 531 spectrometer (MS) .7, 303, 304, 307, 311–313, 320–322, 324, 325, 327, 397, 476 analysis 324, 326, 334, 335, 382 detector 304, 305, 312, 320, 322 spectrum 324 Massoia lactones 231, 241–242 oils 241 Matrix solid-phase dispersion 446 MAX See RP/anion-exchanger (MAX) Maximizing gene expression 478–479 Medicago M sativa 336 M truncatula 336 Melilotic acid 104 Melilotus officinalis 103 Menaquinone 333 Menyanthes trifoliata 517 Metabolic profiling 529–531 NATURAL PRODUCTS ISOLATION 545 Index Metabolome 244, 334, 336, 529, 530 Metabolomics 6, 8, 334–336, 523, 529–531 Methanol (MeOH) 7, 30, 45, 77, 91, 127, 160, 205, 232, 259, 308, 349, 370, 407, 417, 432, 485 Methicillin-resistant Staphylococcus aureus (MRSA) 148, 151, 511 7-Methoxycoumarin 320 3-(3’-Methoxytropoyloxy)-tropane 317 Methyl caffeate 181 (-)-Methylephedrine 331 Methylthiazoyltetrazolium chloride (MTT) 150, 356, 524 MIC See Minimum inhibitory concentration (MIC) Microalgae 85, 86, 442, 520 Microextraction by packed sorbent (MEPS) 446 Microtitre-plate-based antibacterial assay 21–22 Microwave absorbing solvent accelerated distillation (MAD) 99, 100 assisted extraction (MAE) of phenolics 107 assisted hydrodistillation (MAHD) 100 energy 90–92, 94, 97, 109, 419, 420, 439–441 extraction 90, 92, 94, 96, 97, 101, 107, 418, 419, 440 extractors 92, 96, 98, 103, 109 generator 92 hydrodiffusion-gravity (MHG) 100, 102 oven 89, 90, 94, 95, 99, 100, 106, 107, 111, 439 power 90, 91, 95, 98, 101–103, 105–110, 420, 441 source 94 transparent solvent 97, 98, 441 Migrastatin 479 Milbemycin, A4 30-oic acid 493 Milestone Dry Dist microwave apparatus 99 Milling 70, 345, 359, 360, 434 Milton Roy extraction vessel 47 Minimum inhibitory concentration (MIC) 22, 149 MIPs See Molecularly imprinted polymers (MIPs) Mixed mode 197, 198, 205, 206, 215, 216, 445 Mobile phase 124, 7, 16, 24, 119–122, 128, 129, 131, 134, 136, 138, 148, 156, 157, 160, 163, 164, 166, 168–171, 174–179, 192, 196, 210, 213, 214, 222, 224, 227, 232–234, 236–238, 241, 248, 256, 262, 263, 271, 272, 275–277, 279–281, 286, 288, 306, 307, 309, 311, 318, 319, 323, 327, 331, 332, 363, 400, 422–424, 444, 451–453, 478, 482 Modern drug discovery 515–532 Modified Melin Norkrans (MNN) 37, 40 Modifier 45, 51, 53, 55, 60, 61, 64–71, 212, 234–236, 360, 377, 437, 440, 448, 451 Molecular ion 305, 307, 318, 324, 325, 382, 386 modeling 531 motion 90 Molecularly imprinted polymers (MIPs) 431, 447, 448 Monilinia fructicola 487, 488 Monodesmosidic saponin 416 Monosaccharide 416 Monoterpene 56, 99, 100, 324, 336 MRSA See Methicillin-resistant Staphylococcus aureus (MRSA) MS See Mass spectrometer (MS) MTT See Methylthiazoyltetrazolium chloride (MTT) Mucor M plumbeus 502 M spinosus 502 Mueller Hinton Broth (MHB) 150 Multiple development 129, 134, 136, 139, 140 hyphenation 313–314 Mutasynthesis 480, 509 Mycobacterium sp 496, 498 Mycotoxicosis 66 Mycotoxin 66–68, 212, 215 Myricetin 3-O-glucoside 272 3-O-rhamnoside 272 Mytilus 111 Myxococcus xanthus 506 N NAPRALERT See Natural Products Alert (NAPRALERT) NAPROC-13 327 Narcotization 389 Naringenin 429, 506 Natural products databases .327, 519, 530–532 derived drugs 4, 395 discovery 2, 4, 5, 27, 155, 244, 315, 368, 394–396, 515–532 extraction 3–5, 27–40, 43–72, 75–86, 89–112, 190, 369, 397, 473, 522 inspired drugs 519 libraries 5, 386, 508, 517, 531–532 medicine 2–4, 27, 394, 465, 515, 517, 523 research 5–6, 17, 43, 118, 215, 303, 326, 327, 334, 394, 409, 518, 524, 526 Natural Products Alert (NAPRALERT) .128, 383, 532 Neferine 236 Nelumbo nucifera .109, 235, 236 NATURAL PRODUCTS ISOLATION 546 Index Niddamycin A1 241, 242 B 241, 242 F 241, 242 Nitrogen 18, 29–31, 34, 38, 67, 70, 77, 78, 85, 124, 137, 170, 178, 237, 271, 279, 282, 283, 286–288, 299, 304, 317, 335, 346, 363, 374, 381, 467, 478, 504, 505 Nitrogen/phosphorus detector (NPD) 282, 287 Nitrous oxide 45, 61, 64 NMR See Nuclear magnetic resonance (NMR) N-Nornuciferine 108, 236 O-Nornuciferine 108 Nobiletin 61 Non-polar compound 119, 120, 128, 160, 162, 163, 206, 317, 349, 353, 449, 525 solvent 38, 79, 109, 120, 128, 129, 132, 160, 166, 170, 177, 257, 377, 437, 440, 442, 525, 526 Non-sporulating bacteria 36 (-)-Norephedrine 331 Normal phase, prep-HPLC 257–259 (+)-Norpseudoephedrine 331 Nuciferine 108, 235, 236 Nuclear magnetic resonance (NMR) analysis .311, 314, 318, 323, 325, 327, 329, 381, 526, 530 investigation of crude extracts 525–529 solvent 118, 370 spectrometer/spectroscopy 118, 301, 309–312, 314, 386, 396, 471, 526 spectrum 311, 526 O Octadecasilyl (ODS) 121, 147, 162, 171, 212, 271, 272, 323, 327, 334, 335, 421, 422, 502 Octanol 233, 245 ODS See Octadecasilyl (ODS) Odyendyea gabonensis 138 Oligosaccharide 259, 317, 386, 450 Onagraceae 333 Open column chromatography 156 system 94, 95, 104 vessel 90, 441 Opioids 516, 532 Optical activity 18 Optimum separation steps 289–290 Origanum 56, 57 Orthogonal array approach 98 Overlay assay 148, 150 Over pressure thin-layer chromatography (OPTLC) 139 Oxygenated hydrocarbons 258 Oxygenated monoterpene 99, 100 P Pacific Yew tree 63–64 Pacific yew tree 63–64 Paclitaxel 2, 3, 111 Paecilomyces fumosoroseus 66 Panax P ginseng .140, 423, 424 P notoginseng 422–423 P quinquefolium 500–502 Papaver somniferum 2, 146 Paper chromatography 129, 156, 476 8X Parallel HPLC 387–388 Partial identification 323, 326–329, 332, 333, 358 Particle size distribution 61, 109, 124, 131, 256 Partition chromatography 121–122, 155, 223, 224, 236 coefficient 35, 55, 208, 217, 222, 227, 230, 233, 234, 237, 241, 245, 470 PBDEs See Polybrominated diphenyl ethers (PBDEs) PCR See Polymerase chain reaction (PCR) PDA See Photodiode array (PDA) Peak broadening 270 gradient 268 recycling 270 shaving 270 tailing 259, 262, 451, 453 threshold 268 Peganum harmala 236 β-Peltatin 151 Penicillin G 2, 37, 398 Penicillin siamensis 498 Penicillium P brevicompactum 396 P decumbens 494, 495 P griseopurpureum 496–498 P notatum 2, 4, 397, 398 Pentane 45, 120, 127, 128, 160, 448 Pentostatin 406, 408 Peptolide antibiotics 239 Percolation 28, 32, 33, 39, 345–347, 352 Perilla fructescens 334 Pestacia atlantica var mutica 324 Petroleum ether 7, 9, 10, 30, 37, 85, 143, 145, 344, 349, 351, 354, 362, 418, 420, 437, 454, 498 Phaffia rhodozyma 68, 69, 72 Pharmacophore 516, 525 “Phase-trafficking” 190, 207, 216 β-Phellandrene 99 Phellopterin 104 NATURAL PRODUCTS ISOLATION 547 Index Phenol .60, 105, 189, 199, 205, 285, 350, 381, 436, 445 Phenolic acid 106, 107, 140, 428, 430, 435, 436, 446, 448, 450 compound 105–107, 150, 151, 180, 306, 332, 333, 357, 427–428, 455 Phenoxamine synthase expression 478 Phenyl alanine 239, 480–482, 506 2-Phenylchromen-4-one 323 3-Phenylchromen-4-one 323 Phloroglucinol 62, 428, 528 Phoma .477, 478, 481 Phosphomolybdic acid (PMA) 125, 130 Photodiode array (PDA) 9, 11, 62, 64, 264, 301, 302, 305, 306, 313–317, 320–325, 327–336, 397, 474, 476, 477 Photodiode array (PDA) detector 64, 264, 302, 305, 306, 313–315, 320–322, 324, 327, 328, 331, 335, 477 Photoionization detector (PID) 47, 282, 286, 287 Phthalate esters 37, 354, 356, 362, 390 PHWE See Pressurized, hot water extraction (PHWE) Phyllobotryon spathulatum 131 Physical assays 18, 19 treatments 432–434 Physostigmine 143, 144 Phytochemical groups 355–357 Phytoecdysteroid 11–14, 18 pH-zone refining chromatography 234–236 technique 234 Picea abies 502 Picropodophyllin 362 Picrorhiza kurroa 35, 325 PID See Photoionization Detector (PID) Pinguicula lusitanica 333 Piperidine alkaloids 177–179 Planar chromatography 117–152 Plant pigments 122, 155, 354 Plant secondary metabolite .179, 341–363, 427 Plasticizers 37, 362, 381, 389, 390 Platycladus orientalis 102 PLE See Pressurized, liquid extraction (PLE) Plectranthus hereroensis 151 PLPW See Pressurized, low-polarity water (PLPW) extraction PMA See Phosphomolybdic acid (PMA) Podophyllotoxin 362 Podophyllum 362, 520 Polar compound 10, 38, 50, 71, 82, 119, 127, 138, 160, 167, 257, 304, 323, 353, 360, 379, 443–445 Polarimetry 18 Polyacrylamide 164, 510 Polyalthic acid 164, 241, 510 Polybrominated diphenyl ethers (PBDEs) 76, 86 Polygonum cuspidatum 65, 455 Polyketide biosynthesis 480 Polymerase chain reaction (PCR) 382 Polymeric resin 122, 195–196, 445 Polyphenol 60, 69, 82, 107, 209, 217, 323, 349, 353, 357, 405, 427, 430, 438, 442, 446, 447, 450, 453 Polysaccharide 164, 166, 181–183, 190 Polystyrene 164, 195, 196, 200, 201, 210, 214, 258, 259, 404, 450 Ponasterone 11, 13 Poor yield 17 Poppy Powelline 235 Precursor-directed biosynthesis of communesin alkaloids 486–487 of dithiolopyrrolone analogs 484–486 of nonactin 482–484 of squalestatins 481–482 Pregnenolone 111 Pre-isolation 476 Preparation of phytochemically enriched extracts 349–353 Preparative application 276, 286–289, 293–299 gas chromatography (prep-GC) 275–299 high performance liquid chromatography (prep-HPLC) 7, 9, 13, 14, 180, 217, 255–273, 397, 410, 422, 474, 477, 478, 482 high pressure liquid chromatography (prep-HPLC) 7, 9, 13, 14, 130, 180, 217, 222, 255–273, 397, 410, 422, 469, 474, 477, 478, 482 isolation 217, 299, 423, 424, 452, 454–455 plates 132–133 scale .63, 65, 195, 211, 216, 270, 286, 289, 290, 451, 452, 474, 497 thin layer chromatography (PTLC) 7, 11, 124, 130, 132–135, 138, 151 Presaturation 311 Pressurized circular ultra micro (PUM) chamber 139 hot water extraction (PHWE) 443 liquid extraction (PLE) 83, 442–444 low-polarity water (PLPW) extraction 443 microwave-assisted extraction (PMAE) 90 solvent extraction 32–34, 360 system 92, 360 Pristinamycins IA 239 IB 239, 240 IIA 239, 241 IIB 239, 240 NATURAL PRODUCTS ISOLATION 548 Index Proantocyanidin 60 Profiling 10 Progesterone .111, 494, 495 Programmed temperature vaporization (PTV) 284, 299 Propolis 323, 527, 528 Prorocentrum 520 Prostanthera 149 Prostantherol 149 Protein .11, 161, 163, 164, 181, 183, 190, 259, 317, 354, 357, 380, 411, 427, 434, 486, 503, 515, 518, 520 Protoberberine 318 20(S)-Protopanaxatriol 502 Pseudoalteromonas luteoviolacea 205, 215 (+)-Pseudoephedrine 331 Pseudomolecular ion 323, 333 Pseudomonas P acidovorans 498 P aureofaciens 487 P fluorescens 521 Psilocybin 119, 120 Psoralen 320 PTLC See Preparative, thin layer chromatography (PTLC) PTV See Programmed temperature vaporization (PTV) Pulse field gradient 312, 526, 529 PUM chamber See Pressurized, circular ultra micro (PUM) chamber Puqiedine 318 Puqiedine-7-ol 318 Puqiedinone 318 Puqienine A-F 318 Puqietinedinone 318 Puqietinone 318 Puqietinonoside 318 Pyrrolnitrin 487 Q Q-DIS/MARLINÖ 327 QTOF See Quadrupole time-of-flight (QTOF) Quadrupole time-of-flight (QTOF) mass spectrometry 239, 316 Quality control 276, 329–332, 466, 527 Quassinoid 138 Quercetin aglycone 102 3,4’-diglucoside 102 3-glucoside 102 4’-glucoside 102 3-O-glucoside 272 3-O-rhamnoside 272 3-O-rutinoside 272 Quillajaceae 416 Quillaja saponaria 416 Quinolinone alkaloid 328 Quinolizidine alkaloid 317, 332 D-Quinovose (Qui) 416 R Radioimmuno assay (RIA) 13 Radix Angelicae sinensis 107 Ranunculaceae 416 Recombinant technology 470 Recovery of natural products 134–135, 189 Red yeast 68–69, 72 Refractive index (RI) .173, 248, 261, 264, 265, 310, 371 Refractivity 265 Resazurin 8, 20–22 Resin preparation 205, 209–213 Response surface methodology (RSM) 61, 98, 112 Resveratrol 64, 65, 428, 440, 441, 445, 446, 448, 506 Retention time 19, 269, 271, 272, 286, 293, 294, 298, 304, 306, 319, 320, 323–326, 328, 330, 331, 333, 385, 486, 523 Reversed-phase high performance chromatography (RP-HPLC) 181, 211, 451, 452 low pressure chromatography (RP-LPLC) 164 prep-HPLC 257, 259–262, 266, 273, 410 thin layer chromatography (RP-TLC) 121 Rf value 37, 119, 120, 123, 131, 135, 138, 150, 227, 380 Rhizoma Coptidis 109 Rhizopus arrhizus 475, 498 Rhodiola 106 Rhodoquinone 333 RI See Refractive index (RI) RIA See Radioimmuno assay (RIA) Ribes bibersteinii 270–271 RLCCC See Rotary locular counter-current chromatography (RLCCC) Roemerine 236 Rosemarinic acid 335, 444 Rosemary 60, 100, 444 Rosmarinus officinalis 100 Rotary evaporator 13, 14, 31, 38, 83, 135, 170, 180, 270–272, 322, 346, 353 Rotary locular counter-current chromatography (RLCCC) 222, 226 RP/anion-exchanger (MAX) 198, 205, 445 NATURAL PRODUCTS ISOLATION 549 Index RP-HPLC See Reversed-phase, high performance chromatography (RP-HPLC) RP-LPLC See Reversed-phase, low pressure column chromatography (RP-LPLC) RP-TLC See Reversed-phase, thin layer chromatography (RP-TLC) RSM See Response surface methodology (RSM) S Saccharide chains 415, 416 Saccharopolyspora erythraea 506, 507 Saccharothrix algeriensis 484 Safracin B 521 Salkowski reaction 357 Salvia miltiorrhiza 357 3-O-Sambubiosyl-5-O-glucosyl cyanidin 271 Sample application 133, 170, 175–177, 213 elution .175, 176, 178 loading 205, 213, 238, 255, 286 preparation 8, 52–53, 77–79, 81, 83, 85, 90, 256, 291, 330, 348–349, 387, 397, 431–436, 442, 444, 530 work-up 257, 270 Sampling technique for GC .277–279, 311, 432 Sapindaceae 416 Sapindus S mukurossi 416 S saponaria 416 Saponaria officinalis 416 Saponin 351, 357, 416–421, 423, 424 Sarcandra glabra 104 Saussurea medusa 101 SBSE See Stir bar sorptive extraction (SBSE) Scale up to prep-HPLC 268 of xenovulene A 470–471 Scaling up natural products 465–471 Schischkinin 14 SEC See Size exclusion, chromatography (SEC) Secoiridoid .325–326, 333, 336 Secondary metabolite 2, 8, 11, 27–29, 32, 66, 72, 128, 179, 303, 332, 336, 341–363, 377, 378, 382, 396, 403, 408, 427, 466–470, 474, 476, 478–480, 483, 503, 504, 509, 516, 521–523, 526, 529, 530 Secoxyloganin 325 7-butyl ester 325 Sedimentation 434 Seed culture media 468 Selective ion monitoring (SIM) 111, 318, 324 Senna spectabilis 178–179 Sepbox® 388 Sephadex G-10 165, 168 G-15 165 G-25 165 G-100 165 LH-20 .122, 165, 168, 177, 179–183, 384, 421, 450 Sep-Pak Vac 13 Sequential fractionation 69–70 Serine 335 Sesquiterpene hydrocarbon 100 lactone 62, 63, 329, 356 SFE See Supercritical fluid extraction (SFE) SFMAE See Solvent, free microwave-assisted extraction (SFMAE) Shinoda test 356 Shunt metabolites 479 Silanol group 121, 159, 160, 259, 262, 444 Silica gel 7, 16, 20, 37, 118, 124, 127, 128, 131, 134, 137, 138, 142–147, 159–164, 167, 169–171, 174–181, 183, 196–197, 211, 214, 227, 257, 410, 420–422, 498, 502 Silybinins A and B 353 Silybum marianum 353 Silychristin 353 SIM See Selective ion monitoring (SIM) Simaroubaceae 138 Simmondsia chinensis 57 Sinapic acid 428, 433, 435 β-Sitosterol 65, 496, 498 Size exclusion chromatography (SEC) .7, 9, 11, 122, 157, 164, 177–178, 181–183, 259, 372, 378, 526 filtration 434 Size inclusion chromatography 122 sorbent 122 Skytanthine 215 Slurry packing 168 Soft ionization technique 307 Soft-pulse multiple irradiation 311 Solasodine 318 Solidago virga-aurea 416 Solid-liquid extraction 28, 449 Solid-phase extraction (SPE) 7, 54, 171, 173, 190, 264, 303, 328, 354, 363, 371, 431, 444–446, 482 Solid-phase micro-extraction 303, 446 Solubility 10, 44, 45, 48, 53, 55, 71, 76, 91, 97, 99, 104, 121, 164, 216, 234, 245, 260, 266, 270, 290, 344, 350, 353, 399, 402, 430, 436–438, 469, 498, 525 NATURAL PRODUCTS ISOLATION 550 Index Solvent choice 80, 91 elimination approach 306, 307 extraction 10, 11, 19, 28, 32–34, 39, 46, 50, 62, 63, 69, 75–86, 90, 91, 94–98, 100–102, 105–107, 109–111, 346, 360, 397, 418, 420, 431, 432, 434, 436–442, 449, 470, 482 free MHG 102 free microwave-assisted extraction (SFMAE) 90, 97, 99 impurities 210, 353, 469 induced protein precipitation 434 partitioning .7, 10, 351, 372, 384 selection 266, 344–345 system selection 228–233 Sorangium cellulosum 506 Sourcing plant materials 343 Soxhlet extraction 14, 28, 31–33, 39, 104, 272, 345, 347, 419, 436, 442, 522 Soxwave 3.6 96 Soybean .69, 103, 411, 416, 446, 449, 454, 470 SPE See Solid-phase extraction (SPE) (-)-Spectaline 178 SPE-LC-MS 445 Spirastrella spinispirulifera 369 Spirostanol 416 Spirulina platensis 85–86 Spodoptera litura 502 Spongistatin 369 Sporormiella 477 Spray detection 125, 126, 128–131, 134 Squalestatins 231, 243, 401, 477–478, 481–482, 493, 508 Staphylococcus aureus 150, 151, 511 Static cycles 34, 81 time 34, 81 Stationary phase 7, 119, 156, 191, 221, 256, 275, 363, 384, 401, 423, 449, 490 Staurosporines 521 Steam distillation .9, 28, 31, 32, 34, 40, 46, 62, 63, 346, 360 Stemodia maritima 502 Step gradients 13, 14, 129, 170, 171, 176, 177, 180, 214, 234, 272, 498 Steroid .2, 10, 76, 111, 126, 163, 167, 231, 285, 381, 415, 493–498, 526 Steroidal alkaloids 318, 319 Sterol 38, 123, 151, 351, 357, 425, 480, 498 Stilbenes .64, 105, 441, 448 Stir bar sorptive extraction (SBSE) 446 St John’s Wort 62, 521 Stopped-flow 309–311, 318, 322, 333 Streptomyces S antibioticus 478 S avermitilis 491 S cavourensis 493 S coelicolor 504, 506 S coeruleorubidus 490 S djakartensis 241 S hygroscopicus subsp aureolacrimosus 490 S nodosus 402 S olivaceus 402 S peuceticus 490 S platensis 85, 479 S staurosporeus 521 S venezuelae 507 S violaceoruber 504 Structure activity relationship (SAR) 473, 524–525 determination 18, 324, 330 elucidation 7, 17–18, 23, 130, 134, 256, 309, 314, 315, 368, 369, 378, 381, 397, 418, 431, 466, 471, 473, 517, 523, 526 Styrene-divinylbenzene polymers 164, 445 Sublimation Supercritical carbon-di-oxide 44, 51–52, 377 fluid (SCF) 9, 44–46, 50–55, 58, 69–71, 377, 448 fluid extraction (SFE) 43–72, 99, 100, 346, 360, 419–420, 432, 448–449 apparatus 46–48, 59 of astaxanthin 68–69 of capsaicinoid 58–59 of cyclosporine 65–66 of Dandelion leaves 65 of essential oil 56–58 of flavonoid 60–61 GC 49 grade CO2, 49 of jojoba oil 57 of mycotoxins 66–68 of parthenolide 62–63, 329 of polyphenol 60 of resveratrol 64–65 of St John’s Wort 62 of Taxol®, 63–64 Support matrices 194–201, 203, 204, 453 Swainsonine 208, 216, 217 Swarnalin 180 cis-Swarnalin 180, 181 Sweroside 325 Symploca hydnoide 521 Symplostatin 520 Syncephalastrum sp 493 System controller 263 NATURAL PRODUCTS ISOLATION 551 Index T Taguchi method 98 Tamarind 60 Tamarindus indica 60 Tanacetum parthenium 62, 329 Tandem mass spectrometry 307 Tangeretin 61 Tannin .38, 128, 164, 183, 273, 317, 348, 349, 354–355, 357, 427, 429, 430, 438, 452, 525 Tanshen 241 Tanshinone I 241 IIA 241 Taraxacum officinale 65 Taxanes 241, 330 Taxifolin 353, 429 Taxol® 2, 3, 17, 63–64, 231, 239–241 Taxomyces andreanae 123, 520 Taxonomic assignments 368 identification 368, 372, 374, 379, 383 uncertainty 368–369 Taxux T baccata 111 T brevifolia 2, 3, 17, 63, 123, 329 T canadensis 241 TCD See Thermal, connectivity detector (TCD) Teicoplanin A2-2 406, 408 Terpene lactone 61, 62, 69, 70 Terpenoid 2, 38, 63, 76, 128, 142, 480, 498–502, 526 β-Terpineol 99, 502 Tert-butylhydroquinone 438 Testosterone 111, 495 Tetrahydrofuran (THF) 180–181, 232, 236, 259, 261, 266, 273, 320 Tetrahydroprotoberberine 318 1,3,5,6-Tetrahydroxyxanthone 182 Tetraterpenoid 319 Thea sinensis 107 Theophrastus 3, 395 Theoretical capacity 194 Theory of ion-exchange 190–192 Thermal connectivity detector (TCD) 281–282, 286, 287 disorder 90 energy 80, 91 Thermolabile monoterpene 56 sesquiterpene 56 Thermospray 308, 323, 332, 333, 482 Thermostable 317 THF See Tetrahydrofuran (THF) Thiazomycin A 409–410 Thin layer chromatography (TLC) 7, 10, 11, 117–119, 121, 123–125, 127–141, 156, 167, 168, 171, 178, 179, 206, 227, 230, 239, 243, 329, 372, 397, 417, 418, 420, 421, 423, 474, 476, 491, 495, 497, 502 analysis 65, 379–381 bioassays 141–151 bioautographic overlay assay 150–151 direct bioautography 148–150 growth medium 148, 403, 511 plate 16, 20, 24, 37, 118, 124, 129, 130, 132, 135, 139–141, 143, 148–151, 167, 168, 173, 355, 362, 363, 371, 380, 508 Thorough isolation 18, 476–477 Threonine 335 Thymol 502 3-Tigloyloxy-6,7-epoxytropane 317 3-Tigloyloxy-6-isobutyryloxy-7-hydroxytropane 317 TIM See Total ion monitoring (TIM) Time-incubation period 468 Time of flight (TOF) 304, 305, 308, 309, 311, 319, 321, 322, 409, 483 TLC See Thin layer chromatography (TLC) TOCSY See Total correlation spectroscopy (TOCSY ) TOF See Time of flight (TOF) Toluene 36, 50, 79, 109, 120, 127, 128, 147, 228, 440 Total correlation spectroscopy (TOCSY ) 18, 312, 530 Total ion monitoring (TIM) 318 Treponema pallidum 394 Tridesmosidic saponin 416 Triethylamine 128, 178, 235, 236, 262 Trifluoromethane 45, 50 Trifluroacetic acid 128 Trifolium pratense 324 1,3,5-Trihydroxy-3’,3’-dimethyl-2Hpyran[6,7]xanthen-9-one 181 1,3,5-Trihydroxy-6,7-[2’-(1-hydroxy-1-methylethyl)dihydrofurano]-xanthone 182 1,3,5-Trihydroxy-6,7-[2’-(1-methylethenyl)-dihydrfurano]xanthone 181 1,3,5-Trihydroxy-6-O-prenyl-xanthone 181 5,6,7-Trimethoxycoumarin 180 Trimethylsilyl 111, 304, 317 Tripterygium wilfordi 517 Tris(hydroxymethyl)aminomethane 437 Triterpene glycoside 140, 350 saponin 14–16, 109, 110, 336, 416, 420, 421 Trolox® 20 Tropane alkaloid 317, 318 3β-Tropoyloxy-6β-isovaleroyloxytropane 317 3-Tropoyloxy-6-isobutyryloxytropane 317 NATURAL PRODUCTS ISOLATION 552 Index Tryptophan .480, 486, 487 Tubelactomicin A 406, 407 Tween 80 30, 149 Two-dimensional NMR H-13C HMBC 18 H-13C HMQC 18 H-13C HSQC 18 H-1H COSY 18 H-1H COSY-lr 18 H-1H DQF-COSY 18 H-1H NOESY 18 H-1H ROESY 18 H-1H TOCSY (or HOHAHA) 18 HSQC-TOCSY 18 Two-dimensional TLC 139–140 Two-phase system 166, 221, 222, 225, 230 Tyrosine 480, 506 Vibrio alginolyticus 498 cholerae 498, 499 Vinca rosea 3, 17 Vincristine 3, 4, 17 Violacein 205, 215 Virtual screening 531 Vitamin A D E 72 Vitis vinifera 60, 64 7-epi-Vogeloside 325 Volatile compound 51, 56, 79, 293, 324 metabolite 83–85, 99 Voucher specimen .343, 359, 374 U W Ubiquinone 333 Ultra-pressure liquid chromatography (UPLC) 118, 124 Ultrasonic bath 31, 32, 260, 418, 419, 432, 439 extraction 419 Ultrasound-assisted solvent extraction 32–33 Ultraviolet (UV) absorbing bands 134, 320, 385 detection 129, 149, 320, 370, 371, 385 fluorescent indicator 134 indicator .129, 132, 138 visible absorption spectra 306, 320, 323 visible detector 466 visible spectrophotometer 7, 397 visible spectrum 336, 424 Umbelliferone 320, 428 UPLC See Ultra-pressure liquid chromatography (UPLC) Urtica dioica 517 Wagner reagent 355 Wall test 357 Water condenser 94, 108, 110 extraction 7, 353, 417, 443 soluble 38, 165, 353, 370, 415, 418, 449 suppression enhancement through T1 effects 311 Water suppression enhancement (WET) 311 V Yibeinoside A 318 Yield 13, 34, 56, 91, 135, 178, 216, 270, 332, 376, 410, 419, 443, 465, 474, 516 Yucca schidigera 416 Vacuum liquid chromatography (VLC) Valerenic acid 329 Valeriana officinalis 329 Valeric acid 485 Valeryl-pyrrothine 484 van der Waals force 76, 183 Vanillin-sulfuric acid 124, 125, 128, 130, 381 Vanillyl alcohol 105 Verticine N-oxide 318 Verticinone N-oxide 318 Vetiver 57, 58 X Xanthine alkaloid 107 Xanthoceras sorbifolia 110 Xanthone 150, 181, 333, 356 Xanthophyll 319 Xenovulene A 470–471 X-ray crystallography 18, 256 Xylene 40 D-Xylose (Xyl) 416 Y Z Zaragozic acid 401, 477 Zuelania guidonia 138 Zushima 320, 321 Zwitterionic phases 202–205 Zygophyllum album 99 ... 3 )- -Larabinopyranosyl)oxy ]-2 3-oxo-olean-12-en-28-oic acid β-D-glucopyranoside, 3 -[ (O-β-D-glucopyranosyl-(1 → 3 )- -L-arabinopy ranosyl)oxy ]-2 7-oxo-olean-12-en-28-oic acid β-D-glucopyranoside, 3-O-α-L-arabinopyranosyl... 3 -[ (O-β-D-glucopyranosyl-(1 → 3 )- -L-arabinopyranosyl)oxy ]-2 3-oxo-olean-12-en-28-oic acid β-D-glucopyranoside and 3 -[ (O-β-D-glucopyranosyl-(1 → 3 )- -L-arabinopyranosyl)oxy ]-2 7-oxo-olean-12-en-28-oic acid β-D-glucopyranoside,... 3 )- -L-arabinopyranosyl)oxy ]-2 3-oxo-olean-12-en-28oic acid β-D-glucopyranoside R = - -D-glucopyranosyl-(1 3 )- -L-arabinopyranosyl O HO OH OH O O CHO HO RO 3 -[ (O-β-D-glucopyranosyl-(1 3 )- -L-arabinopyranosyl)oxy ]-2 7-oxo-olean-12-en-28oic