Progress in the Chemistry of Organic Natural Products 105

221 Pages·2017·7.33 MB·English

by  A. Douglas Kinghorn

Progress in the Chemistry of Organic Natural Products
A. Douglas Kinghorn
Heinz Falk
Simon Gibbons
Jun'ichi Kobayashi Editors
105
Progress in the
Chemistry of
Organic Natural
Products
Progress in the Chemistry of Organic Natural
Products
FoundedbyLa´szlo´ Zechmeister
SeriesEditors
A.DouglasKinghorn,Columbus,OH,USA
HeinzFalk,Linz,Austria
SimonGibbons,London,UK
Jun’ichiKobayashi,Sapporo,Japan
HonoraryEditor
WernerHerz,Tallahassee,FL,USA
EditorialBoard
GiovanniAppendino,Novara,Italy
VerenaDirsch,Vienna,Austria
NicholasH.Oberlies,Greensboro,NC,USA
YangYe,Shanghai,PRChina
Moreinformationaboutthisseriesathttp://www.springer.com/series/10169
A. Douglas Kinghorn (cid:129) Heinz Falk (cid:129)
Simon Gibbons (cid:129) Jun’ichi Kobayashi
Editors
Progress in the Chemistry of
Organic Natural Products
Volume 105
With contributions by
H. Ashihara (cid:1) A. Crozier (cid:1) K. Mizuno (cid:1) T. Yokota
C. Lavaud (cid:1) G. Massiot
W. Robien
Editors
A.DouglasKinghorn HeinzFalk
DivisionofMedicinalChemistry& InstituteofOrganicChemistry
Pharmacognosy,CollegeofPharmacy JohannesKeplerUniversityLinz
TheOhioStateUniversity Linz,Austria
Columbus,Ohio
USA
SimonGibbons Jun’ichiKobayashi
ResearchDepartmentofPharmaceutical GraduateSchoolofPharmaceuticalScience
andBiologicalChemistry HokkaidoUniversity
UCLSchoolofPharmacy Sapporo,Japan
London,UnitedKingdom
ISSN2191-7043 ISSN2192-4309 (electronic)
ProgressintheChemistryofOrganicNaturalProducts
ISBN978-3-319-49711-2 ISBN978-3-319-49712-9 (eBook)
DOI10.1007/978-3-319-49712-9
LibraryofCongressControlNumber:2017933078
©SpringerInternationalPublishingAG2017
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Contents
XanthineAlkaloids:Occurrence,Biosynthesis,andFunction
inPlants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
HiroshiAshihara,KouichiMizuno,TakaoYokota,andAlanCrozier
TheIbogaAlkaloids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
CatherineLavaudandGeorgesMassiot
ACriticalEvaluationoftheQualityofPublished
13CNMRDatainNaturalProductChemistry. . . . . . . . . . . . . . . . . . . . 137
WolfgangRobien
ListedinPubMed
v
Xanthine Alkaloids: Occurrence,
Biosynthesis, and Function in Plants
HiroshiAshihara,KouichiMizuno,TakaoYokota,andAlanCrozier
Contents
1 Introduction................................................................................... 2
2 OccurrenceofXanthineAlkaloidsinthePlantKingdom.................................. 6
2.1 Ericales(TeaandRelatedSpecies).................................................... 6
2.2 Gentianales(CoffeeandRelatedSpecies)............................................ 10
2.3 Aquifoliales(Mate´andRelatedSpecies).............................................. 13
2.4 Malvales(Cacao,Cola,andRelatedSpecies)......................................... 14
2.5 Sapindales(Guarana´,Citrus,andRelatedPlants).................................... 17
2.6 OtherSpecies........................................................................... 20
3 BiosynthesisofXanthineAlkaloids......................................................... 21
3.1 ABriefHistoryoftheElucidationoftheBiosynthesisPathways................... 21
3.2 CaffeineBiosynthesisPathwaysfromXanthosine.................................... 25
3.2.1 Formationof7-Methylxanthine............................................... 27
3.2.2 Conversionof7-MethylxanthinetoCaffeineviaTheobromine............. 30
3.2.3 EvolutionaryRelationshipoftheCaffeineSynthaseFamilyProteins....... 33
3.3 PathwaysthatSupplyXanthosineforCaffeineBiosynthesis........................ 37
3.3.1 DeNovoRoute................................................................. 37
3.3.2 AMPRoute..................................................................... 40
3.3.3 SAMCycleRoute.............................................................. 40
3.3.4 NADRoute..................................................................... 41
3.3.5 GMPRoute..................................................................... 42
3.4 LocalizationofXanthineAlkaloidBiosynthesis...................................... 42
3.4.1 OrgansandTissues............................................................ 43
H.Ashihara(*)
DepartmentofBiology,OchanomizuUniversity,Tokyo112-8610,Japan
e-mail:[email protected]
K.Mizuno
FacultyofBioresourceofScience,AkitaPrefecturalUniversity,Akita010-0195,Japan
e-mail:[email protected]
T.Yokota
DepartmentofBiosciences,TeikyoUniversity,Utsunomiya320-8551,Japan
e-mail:[email protected]
A.Crozier
DepartmentofNutrition,UniversityofCalifornia,Davis,CA951616,USA
e-mail:[email protected]
©SpringerInternationalPublishingAG2017 1
A.D.Kinghorn,H.Falk,S.Gibbons,J.Kobayashi(eds.),ProgressintheChemistry
ofOrganicNaturalProducts105,DOI10.1007/978-3-319-49712-9_1
2 H.Ashiharaetal.
3.4.2 SubcellularAccumulationofXanthineAlkaloids............................ 45
3.4.3 SubcellularLocalizationofCaffeineBiosynthesisEnzymes................ 45
3.4.4 SubcellularLocalizationandTransportofIntermediates.................... 48
3.5 RegulationofCaffeineBiosynthesis.................................................. 48
4 MetabolismofXanthineAlkaloids.......................................................... 49
4.1 MethyluricAcidBiosynthesis......................................................... 49
4.2 BiodegradationandInter-conversionofXanthineAlkaloids......................... 50
4.2.1 TheMajorPathwayofCaffeineDegradation................................. 50
4.2.2 ConventionalPurineCatabolicPathwaysinPlants........................... 51
4.2.3 DiversityofXanthineAlkaloidMetabolisminPlants........................ 52
4.2.4 XanthineAlkaloidMetabolisminBacteriaandAnimals.................... 59
5 EcologicalRolesofXanthineAlkaloids.................................................... 61
5.1 AllelopathicFunctionTheory.......................................................... 61
5.1.1 EffectofXanthineAlkaloidsonGerminationandGrowthofPlants........ 63
5.1.2 EffectofXanthineAlkaloidsonProliferationofPlantCells................ 64
5.1.3 EffectofXanthineAlkaloidsonPlantMetabolism.......................... 64
5.1.4 EffectofCaffeineonProteinExpressionProfiles............................ 65
5.1.5 AllelopathyinNaturalEcosystems............................................ 66
5.2 ChemicalDefenseTheory............................................................. 66
5.2.1 ChemicalDefenseAgainstMicroorganismsandAnimals................... 66
5.2.2 ProofoftheChemicalDefenseTheoryDemonstrated
withTransgenicPlants......................................................... 67
6 BiotechnologyofXanthineAlkaloids....................................................... 67
6.1 DecaffeinatedCoffeeandTeaPlants.................................................. 68
6.2 Caffeine-ProducingTransgenicPlants................................................ 70
6.2.1 AntiherbivoreActivity......................................................... 71
6.2.2 AntipathogenActivity......................................................... 71
7 SummaryandPerspectives................................................................... 74
References........................................................................................ 75
1 Introduction
Xanthinealkaloids,alsoknownaspurinealkaloids,consistofmethylxanthinesand
methyluricacidsandtheirstructuresarebasedonthexanthine(1)anduricacid(9)
skeletons (Fig. 1). Caffeine (1,3,7-trimethylxanthine) (8) and theobromine
(3,7-dimethylxanthine) (5)occur inplantspecies such ascoffee (Coffeaarabica),
tea(Camelliasinensis),mate´(Ilexparaguariensis),cacao(Theobromacacao),and
guarana´ (Paullinia cupana), which are used for popular non-alcoholic beverages
[1].Theisolationof8fromcoffeeseedswasfirstreportedindependentlyin1820by
the German researchers, Runge [2] and von Giese [3]. Caffeine (8) was found as
“thein” in tea leaves by Oudry [4] in 1827. Subsequently, it was also detected in
mate´ byStenhouse[5]in1843andinkolanuts(Colaacuminata)byDaniell[6]in
1865. Theobromine (5) was discovered in cacao seeds by Woskresensky [7] in
1842. Paraxanthine (1,7-dimethylxanthine) (7) was isolated from human urine by
Salomon[8]in1883,butitwasnotdetectedincoffeeseedsuntil1980byChouand
XanthineAlkaloids:Occurrence,Biosynthesis,andFunctioninPlants 3
(a)
O
O O H O
HN HN HN N HN N N HN
O N N
O N N O N N O N N
H H H
1 (xanthine) 2 (7-methylxanthine) 3 (3-methylxanthine) 4 (1-methylxanthine)
O O O
O H
HN N N N N N N N
O N N O N N O NH N O N N
5 (theobromine) 6 (theophylline) 7 (paraxanthine) 8 (caffeine)
O O O O
H H
HN N N N N N N N
O O O O
O NH NH O N N O N N O N N
9 (uric acid) 10 (theacrine) 11 (methylliberine) 12 (liberine)
O
NH2 O O HN N
N N N N N N O N N
N NH H2N NH NH NH NH HO H
O
13 (adenine) 14 (guanine) 15 (hypoxanthine)
OH OH
16 (xanthosine)
O
N
HN
O
O O NH N O O OH
HHOO P O O N OH N NH2 N
OH OH
17 (XMP; xanthosine-5'- 18 (nicotinic acid) 19 (nicotinamide) 20 (trigonelline)
monophosphate)
Fig.1 (a)Structuresof1–20.(b)Structuresof21–36.(c)Structuresof37–51.(d)Structuresof
52–61
Waller[9].Thecompletechemicalsynthesisof8wasreportedbyFischerandAch
[10]in1895.
Studies on caffeine biosynthesis were initiated in the 1960s, while highly
purified caffeine synthase was isolated by Kato et al. [11] in 1999 and the gene
encoding this enzyme was cloned in 2000 [12]. The major caffeine biosynthesis
pathway, of xanthosine (16)!7-methylxanthosine (23)!7-methylxanthine
(2)!theobromine (5)!caffeine (8), is now confirmed at both the biochemical
andmolecularlevel.
Initially, caffeine (8) was considered to be a waste end-product in plants,
althoughitwasalsohypothesizedthatthispurinealkaloidplaysaroleinchemical
4 H.Ashiharaetal.
(b)
O O O O
HN N HN N HN N HN N
H2N N N H2N NH N O NH N O NH N
O O
HO P O HO HO HO P O
OH O O O OH O
OH OH OH OH OH OH OH OH
21 (7-methyl-GMP) 22 (7-methylguanosine) 23 (7-methylxanthosine) 24 (7-methyl-XMP)
NH2 NH2 O
N N N N N N NH2
N N N N H2N N N N N
O
O O O N N
S
HO P O HO P O HO P O HO O
OH O OH O OH O NH2
OH OH OH OH OH OH OH OH
25 (1-methyl-AMP) 26 (7-methyl-AMP) 27 (1-methyl-GMP) 28 (S-adenosyl-L-methionine)
O NH2 O O
HN N N N HN N HN N
H2N N N N N N N H2N NH N
O O O
HO P O HO P O HO P O HO
OH O OH O OH O O
OH OH OH OH OH OH OH OH
29 (GMP) 30 (AMP) 31 (IMP) 32 (guanosine)
NH2 O O
N N NH2 O H2N OH
N N N O NH2 35 (glycine)
O O HO P O N
O O P O P O O O O N O O
OH O N O OH
OH OH OH OH OH OH NH2
33 (NAD) 34 (nicotinamide mononucleotide) 36 (azaserine)
Fig.1 (continued)
defenses and had an allelopathic function [13]. Recent research using transgenic
plantshasprovidedconvincingevidenceforthechemicaldefensetheory[14].
A comprehensive review of xanthine alkaloid metabolism was published over
15yearsagobyAshiharaandCrozier[13].Thepresentcontributionwillfocuson
findings published since 2000, while background information, such as general
purine metabolism and various hypotheses on caffeine biosynthesis, which were
coveredintheinitialreview[13],willnotbedescribedhereindetail.Thephysical
andchemicalpropertiesofxanthinealkaloids,whicharenotatopicofthischapter,
havebeensummarizedbyTarkaandHurst[15].