Modern Alkaloids - Structure, Isolation, Synthesis and Biology

691 Pages·2008·7.67 MB·English

Modern Alkaloids
Edited by
Ernesto Fattorusso and
OrazioTaglialatela-Scafati
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Modern Alkaloids
Structure, Isolation, Synthesis and Biology
Edited by
Ernesto Fattorusso and Orazio Taglialatela-Scafati
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ISBN: 978-3-527-31521-5
V
Contents
Preface XVII
List of Contributors XIX
I BioactiveAlkaloids:StructureandBiology 1
1 EcologicalRolesofAlkaloids 3
MichaelWink
1.1 Introduction:DefenseStrategiesinPlants 3
1.2 EcologicalRolesofAlkaloids 4
1.3 ModesofAction 9
1.3.1 UnspecificInteractions 11
1.3.2 SpecificInteractions 12
1.3.3 CytotoxicityofAlkaloids 16
1.4 EvolutionofAlkaloidalDefenseSystems 19
1.5 Conclusions 23
2 AntitumorAlkaloidsinClinicalUseorinClinicalTrials 25
MurielCuendet,JohnM.Pezzuto
2.1 Introduction 25
2.2 AntitumorAlkaloidsinClinicalUse 25
2.2.1 VincaAlkaloids 25
2.2.1.1 Vinblastine(VLB,1) 28
2.2.1.2 Vincristine(VCR,2) 28
2.2.1.3 Vindesine(VDS,3) 28
2.2.1.4 Vinorelbine(VRLB,4) 29
2.2.1.5 Vinflunine(VFL,5) 29
2.2.2 CamptothecinandAnalogs 29
2.2.2.1 Camptothecin(CPT,6) 31
2.2.2.2 Irinotecan(CPT-11) 31
2.2.2.3 Topotecan 32
2.2.2.4 Exatecan 32
2.2.2.5 Gimatecan 32
ModernAlkaloids:Structure,Isolation,SynthesisandBiology.EditedbyE.FattorussoandO.Taglialatela-Scafati
Copyright(cid:1)2008WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-31521-5
VI Contents
2.2.2.6 Karenitecin 32
2.2.2.7 Lurtotecan 32
2.2.2.8 Rubitecan(9-nitrocamptothecin) 33
2.2.3 Taxanes 33
2.2.3.1 Paclitaxel 33
2.2.3.2 Docetaxel 35
2.3 AntitumorAlkaloidsinClinicalTrials 36
2.3.1 Ecteinascidin-743(Yondelis,Trabectedin) 36
2.3.2 7-Hydroxystaurosporine(UCN-01) 37
2.3.3 EllipticineandAnalogs 37
2.3.4 AcronycineandAnalogs 38
2.3.5 ColchicineandAnalogs 39
2.3.6 Ukrain 40
2.4 AlkaloidsUsedforMDRReversal 40
2.4.1 CinchonaAlkaloids 40
2.4.2 DofequidarFumarate(MS-209) 41
2.5 AlkaloidsUsedforCancerPrevention 42
2.6 Conclusions 43
2.7 Acknowledgments 44
3 AlkaloidsandtheBitterTaste 53
AngelaBassoli,GigliolaBorgonovo,GilbertoBusnelli
3.1 Introduction 53
3.2 TheBitterTasteChemoreceptionMechanism 54
3.3 BitterAlkaloidsinFood 58
3.4 TheBitterTasteofAlkaloidsinOtherDrugsandPoisons 63
3.5 AlkaloidsandTasteinInsects 66
3.6 TheBitterTasteofAlkaloids:ShouldWeAvoid,Mask,or
Understand? 69
3.7 Acknowledgments 70
4 CapsaicinandCapsaicinoids 73
GiovanniAppendino
4.1 Introduction 73
4.2 WhatIsanAlkaloid?IsCapsaicinanAlkaloid? 73
4.3 Diversity,Biosynthesis,andMetabolismofCapsaicinoids 77
4.4 QuantizationofCapsaicinoidsandTheirDistributioninChili
Pepper 83
4.5 IsolationandSynthesisofCapsaicin 86
4.6 TRV1astheBiologicalTargetofCapsaicinandtheEcologicalRaison
d’eˆtreofCapsaicinoids:AMolecularView 90
4.7 NaturallyOccurringAnalogsandAntagonistsofCapsaicin
andEndogenousVanilloids 93
4.8 Structure–ActivityRelationshipsofCapsaicinoids 94
Contents VII
4.9 MolecularGastronomyofHotFood 98
4.9.1 BiomedicalRelevanceofCapsaicin-InducedTrigeminal
Responses 98
4.9.2 EffectofCapsaicinonTaste 98
4.9.3 GustatorySweating 99
4.9.4 GustatoryRhinitis 99
4.9.5 HotFoodMitridatism 99
4.9.6 EffectofCapsaicinonDigestion 100
4.9.7 CapsaicinandStomachCancer 100
4.9.8 TheEffectofAgeandSexontheSensitivitytoCapsaicin 100
4.9.9 CapsaicinasaSlimmingAgent 101
4.9.10 QuenchingCapsaicin 101
4.9.11 ChiliesandOliveOil 102
4.9.12 WhoShouldAvoidChilies? 102
4.9.13 HowcanthePungencyofChiliesbeModerated? 102
4.9.14 PsychologyofPepperConsumption 102
4.10 Conclusions 103
4.11 Acknowledgments 103
5 Glycosidase-InhibitingAlkaloids:Isolation,Structure,and
Application 111
NaokiAsano
5.1 Introduction 111
5.2 IsolationandStructuralCharacterization 111
5.2.1 DeoxynojirimycinandRelatedCompounds 112
5.2.1.1 IsolationfromMorusspp.(Moraceae) 112
5.2.1.2 IsolationfromThaiMedicinalPlants‘‘Thopthaep’’and‘‘Cha
EmThai’’ 113
5.2.2 a-HomonojirimycinandRelatedCompounds 115
5.2.2.1 IsolationfromGardenPlants 115
5.2.2.2 IsolationfromtheThaiMedicinalPlant‘‘NonTaiYak’’ 117
5.2.2.3 IsolationfromAdenophoraspp.(Campanulaceae) 117
5.2.3 IndolizidineandPyrrolizidineAlkaloids 117
5.2.3.1 IsolationfromtheLeguminosaeFamily 118
5.2.3.2 IsolationfromtheHyacinthaceaeFamily 120
5.2.4 NortropaneAlkaloids 122
5.2.4.1 IsolationfromtheSolanaceaeFamily 123
5.2.4.2 IsolationfromtheConvolvulaceaeFamily 124
5.3 BiologicalActivitiesandTherapeuticApplication 125
5.3.1 AntidiabeticAgents 125
5.3.1.1 a-GlucosidaseInhibitors 125
5.3.1.2 GlycogenPhosphorylaseInhibitors 128
5.3.1.3 HerbalMedicines 128
5.3.2 MolecularTherapyforLysosomalStorageDisorders 129
VIII Contents
5.3.2.1 SubstrateReductionTherapy 130
5.3.2.2 PharmacologicalChaperoneTherapy 130
5.4 ConcludingRemarksandFutureOutlook 133
6 NeurotoxicAlkaloidsfromCyanobacteria 139
RashelV.Grindberg,CynthiaF.Shuman,CarlaM.Sorrels,JoshWingerd,
WilliamH.Gerwick
6.1 Introduction 139
6.2 NeurotoxicAlkaloidsofPrincipallyFreshwaterandTerrestrial
Cyanobacteria 141
6.2.1 Anatoxin-a,Homoanatoxin-a,Anatoxin-a(s),andAnalogs 141
6.2.1.1 Anatoxin-a 142
6.2.1.2 Homoanatoxin-a 145
6.2.1.3 Anatoxin-a(s) 145
6.2.2 b-Methylaminoalanine 146
6.2.3 Saxitoxin 151
6.3 NeurotoxicAlkaloidsofMarineCyanobacteria 156
6.3.1 AntillatoxinAandB 156
6.3.2 JamaicamideA,B,andC 158
6.3.3 Kalkitoxin 161
6.4 Conclusion 162
7 LamellarinAlkaloids:StructureandPharmacologicalProperties 171
J´erˆomeKluza,PhilippeMarchetti,ChristianBailly
7.1 Introduction 171
7.2 TheDiscoveryofLamellarins 172
7.3 ModulationofMultidrugResistance 174
7.4 AntioxidantProperties 176
7.5 InhibitionofHIV-1Integrase 176
7.6 Cytotoxicity 177
7.7 TopoisomeraseIInhibition 178
7.8 TargetingofMitochondriaandProapoptoticActivities 180
7.9 Conclusion 184
8 ManzamineAlkaloids 189
JiangnanPeng,KarumanchiV.Rao,Yeun-MunChoo,MarkT.Hamann
8.1 Introduction 189
8.2 ManzamineAlkaloidsfromMarineSponges 191
8.2.1 b-Carboline-containingManzamineAlkaloids 191
8.2.1.1 ManzamineAType 191
8.2.1.2 ManzamineBType 195
8.2.1.3 ManzamineCType 196
8.2.1.4 Otherb-Carboline-containingManzamines 196
8.2.2 Ircinal-relatedAlkaloids 198
8.3 SourceandLarge-scalePreparationofManzamineAlkaloids 202
Contents IX
8.3.1 SourceofManzamineAlkaloids 202
8.3.2 Large-scalePreparationofManzamines 204
8.3.3 SupercriticalFluidChromatographySeparationofManzamine
Alkaloids 205
8.4 SynthesisofManzamineAlkaloids 206
8.4.1 TotalSynthesisofManzamineAandRelatedAlkaloids 206
8.4.2 TotalSynthesisofManzamineC 208
8.4.3 TotalSynthesisofNakadomarinA 214
8.4.4 SyntheticStudiesofManzamineAlkaloids 216
8.4.5 StudiesonBiomimeticSynthesis 217
8.4.6 SynthesisofManzamineAnalogs 219
8.5 BiologicalActivitiesofManzamines 220
8.5.1 AnticancerActivity 220
8.5.2 AntimalarialActivity 222
8.5.3 AntimicrobialandAntituberculosisActivity 224
8.5.4 MiscellaneousBiologicalActivities 225
8.6 ConcludingRemarks 226
9 AntiangiogenicAlkaloidsfromMarineOrganisms 233
AnaR.Diaz-Marrero,ChristopherA.Gray,LianneMcHardy,KaoruWarabi,
MichelRoberge,RaymondJ.Andersen
9.1 Introduction 233
9.2 PurineAlkaloids 235
9.3 TerpenoidDerivatives 236
9.3.1 Avinosol 236
9.3.2 CortistatinsA–D 237
9.3.3 Squalamine 238
9.4 Motuporamines 240
9.5 Pyrrole-ImidazoleAlkaloids:‘‘Oroidin’’-RelatedAlkaloids 244
9.5.1 AgelastatinA 245
9.5.2 AgeladineA 247
9.6 Tyrosine-derivedAlkaloids 250
9.6.1 Aeroplysinin-1 250
9.6.2 PsammaplinA 254
9.6.3 Bastadins 256
9.7 Tryptophan-derivedAlkaloids 259
9.8 Ancorinosides 262
9.9 ConcludingRemarks 263
10 ATypicalClassofMarineAlkaloids:Bromopyrroles 271
AnnaAiello,ErnestoFattorusso,MarialuisaMenna,
OrazioTaglialatela-Scafati
10.1 Introduction 271
10.2 Oroidin-likeLinearMonomers 273
10.3 PolycyclicOroidinDerivatives 278