Amino Acids, Peptides and Proteins in Organic Chemistry 3: Building Blocks, Catalysis and Coupling Chemistry (Amino Acids, Peptides and Proteins in Organic Chemistry (VCH))

595 Pages·2011·5.87 MB·English

by  Andrew B. Hughes

Edited by
Andrew B. Hughes
Amino Acids, Peptides and
Proteins in Organic
Chemistry
Further Reading
Drauz, K.,Gröger,H., May,O. (eds.) Lutz, S., Bornscheuer,U. T. (eds.)
Enzyme Catalysis in Organic Protein Engineering Handbook
Synthesis 2VolumeSet
Thirdcompletelyrevised 2009
andenlargededition
ISBN:978-3-527-31850-6
3Volumes
2011 Sewald, N., Jakubke,H.-D.
ISBN:978-3-527-32547-4
Peptides: Chemistry
and Biology
Fessner,W.-D.,Anthonsen, T.
Modern Biocatalysis 2009
ISBN:978-3-527-31867-4
StereoselectiveandEnvironmentally
FriendlyReactions
Jakubke, H.-D., Sewald, N.
2009
Peptides from A to Z
ISBN:978-3-527-32071-4
AConciseEncyclopedia
Pignataro, B.(ed.)
2008
Ideas in Chemistry and ISBN:978-3-527-31722-6
Molecular Sciences
Royer,J. (ed.)
AdvancesinSyntheticChemistry
Asymmetric Synthesis of
2010
Nitrogen Heterocycles
ISBN:978-3-527-32539-9
2009
Reek, J.N.H.,Otto,S. ISBN:978-3-527-32036-3
Dynamic Combinatorial
Hecht,S., Huc,I. (eds.)
Chemistry
Foldamers
2010
Structure,Properties,andApplications
ISBN:978-3-527-32122-3
2007
ISBN:978-3-527-31563-5
Edited by
Andrew B. Hughes
Amino Acids, Peptides and Proteins
in Organic Chemistry
Volume 3 - Building Blocks, Catalysis and
Coupling Chemistry
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ISBN:978-3-527-32102-5
V
Contents
List of Contributors XVII
PartOne AminoAcidsasBuildingBlocks 1
1 AminoAcidBiosynthesis 3
EmilyJ.ParkerandAndrewJ.Pratt
1.1 Introduction 3
1.2 GlutamateandGlutamine:GatewaystoAminoAcidBiosynthesis 5
1.2.1 CaseStudy:GOGAT:GATsandMultifunctionalEnzymes
inAminoAcidBiosynthesis 6
1.3 OtherAminoAcidsfromUbiquitousMetabolites:Pyridoxal
Phosphate-DependentRoutestoAspartate,Alanine,andGlycine 8
1.3.1 PyridoxalPhosphate:ACriticalCofactorofAminoAcidMetabolism 8
1.3.2 CaseStudy:DualSubstrateSpecificityofFamilies
ofAminotransferaseEnzymes 10
1.3.3 PLPandtheBiosynthesisofAlanineandGlycine 15
1.4 RoutestoFunctionalizedThree-CarbonAminoAcids:Serine,
Cysteine,andSelenocysteine 16
1.4.1 SerineBiosynthesis 16
1.4.2 CysteineBiosynthesis 18
1.4.3 CaseStudy:GenomeInformationasaStartingPointforUncovering
NewBiosyntheticPathways 19
1.4.3.1 CysteineBiosynthesisinMycobacteriumTuberculosis 19
1.4.3.2 CysteineBiosynthesisinArchaea 20
1.4.3.3 RNA-DependentBiosynthesisofSelenocysteineandOther
AminoAcids 21
1.5 OtherAminoAcidsfromAspartateandGlutamate:Asparagine
andSideChainFunctionalGroupManipulation 22
1.5.1 AsparagineBiosynthesis 23
AminoAcids,PeptidesandProteinsinOrganicChemistry.
Vol.3–BuildingBlocks,CatalysisandCouplingChemistry.EditedbyAndrewB.Hughes
Copyright(cid:1)2011WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-32102-5
VI Contents
1.6 AspartateandGlutamateFamiliesofAminoAcids 25
1.6.1 Overview 25
1.6.2 AspartateFamilyAminoAcids:ThreonineandMethionine 25
1.6.2.1 CaseStudy:EvolutionofLeavingGroupSpecificityinMethionine
Biosynthesis 28
1.6.2.2 Threonine,Homocysteine,andPLP 30
1.6.2.3 ThreonineSynthase 30
1.6.2.4 Methionine,Cysteine,andCystathionine 32
1.6.2.5 MethionineSynthase 33
1.6.3 GlutamateFamilyAminoAcids:ProlineandArginine 33
1.7 BiosynthesisofAliphaticAminoAcidswithModifiedCarbonSkeletons:
Branched-ChainAminoAcids,Lysine,andPyrrolysine 37
1.7.1 Overview 37
1.7.2 ValineandIsoleucine 37
1.7.3 Homologationofa-KetoAcids,andtheBiosynthesisofLeucine
anda-AminoadipicAcid 41
1.7.4 BiosynthesisofLysine:ASpecialCase 44
1.7.4.1 DiaminopimelatePathwaytoLysine 44
1.7.4.2 a-AminoadipicAcidPathwaystoLysine 45
1.7.4.3 Pyrrolysine 47
1.8 BiosynthesisoftheAromaticAminoAcids 49
1.8.1 ShikimatePathway 49
1.8.2 CaseStudy:AlternativeSynthesisofDehydroquinateinArchaea 53
1.8.3 BiosynthesisofTryptophan,Phenylalanine,andTyrosinefrom
Chorismate 58
1.8.3.1 TryptophanBiosynthesis 58
1.8.3.2 PhenylalanineandTyrosineBiosynthesis 59
1.8.4 HistidineBiosynthesis 61
1.9 Conclusions 64
References 65
2 HeterocyclesfromAminoAcids 83
M.IsabelCalazaandCarlosCativiela
2.1 Introduction 83
2.2 HeterocyclesGeneratedbyIntramolecularCyclizations 83
2.2.1 a-Lactonesanda-Lactams 83
2.2.2 Indolines 84
2.2.3 AziridinecarboxylicAcidsandOxetanones 86
2.2.4 b-LactamsandPyroglutamicAcidDerivatives 87
2.2.5 AminoLactamsandAminoAnhydrides 88
2.2.6 AzacycloalkanecarboxylicAcids 89
2.3 HeterocyclesGeneratedbyIntermolecularCyclizations 89
2.3.1 MetalComplexes 89
2.3.2 a-AminoAcidN-CarboxyanhydridesandHydantoins 90
2.3.3 OxazolidinonesandImidazolidinones 91
Contents VII
2.3.4 Oxazolones 93
2.3.5 OxazinonesandMorpholinones,Pyrazinones
andDiketopiperazines 94
2.3.6 Tetrahydroisoquinolinesandb-Carbolines 96
2.3.7 Oxazo/Thiazolidinones,Oxazo/Thiazolidines,
andOxazo/Thiazolines 97
2.3.8 Sulfamidates 101
2.3.9 Tetrahydropyrimidinones 102
2.4 HeterocyclesGeneratedbyCycloadditions 102
2.5 Conclusions 104
2.6 ExperimentalProcedures 104
2.6.1 Synthesisof1-tert-Butyl-3-phenylaziridinone(5) 104
2.6.2 SynthesisofDimethyl(2S,3aR,8aS)-1,2,3,3a,8,8a-
Hexahydropyrrolo[2,3-b]indole-1,2-dicarboxylate(Precursorof10) 105
2.6.3 SynthesisofBenzyl(R)-1-Tritylaziridine-2-carboxylate(15) 105
2.6.4 Synthesisof(S)-N-tert-Butoxycarbonyl-3-aminooxetan-2-one(18) 106
2.6.5 Synthesisof(S)-1-(tert-Butyldimethylsilyl)-4-oxoazetidine-
2-carboxylicAcid(24) 106
2.6.6 Synthesisof9H-Fluoren-9-ylmethyl(R)-Hexahydro-2-oxo-1H-azepin-
3-ylCarbamate(31) 106
2.6.7 SynthesisofEthyl(S)-N-(tert-Butoxycarbonyl)-a-
(tert-butoxymethyl)prolineEster(36) 107
2.6.8 SynthesisofProlineN-Carboxyanhydride(49) 107
2.6.9 Synthesisof(2S,4S)-2-Ferrocenyl-3-pivaloyl-4-methyl-1,3-
oxazolidin-5-one(54b) 107
2.6.10 Synthesisof(6S)-6-Isopropyl-5-phenyl-3,6-dihydro-2H-1,4-oxazin-2-
one(71) 108
2.6.11 Synthesisof(3S,6R)-6-Isopropyl-3-methyl-5-phenyl-1,2,3,6-
tetrahydro-2-pyrazinone(78) 108
2.6.12 Synthesisof(3S)-3,6-Dihydro-2,5-dimethoxy-3-
isopropylpyrazine(85) 109
2.6.13 Synthesisof(3S)-1,2,3,4-Tetrahydroisoquinoline-
3-carboxylicAcid(87) 110
2.6.14 SynthesisofMethyl(S)-N-tert-Butoxycarbonyl-2,2-dimethyloxazolidine-
4-carboxylate(109) 110
2.6.15 Synthesisof(2S,6S)-2-tert-Butyl-1-carbobenzoxy-4-oxopyrimidin-6-
carboxylicAcid(126) 111
References 111
3 Radical-MediatedSynthesisofa-AminoAcidsandPeptides 115
JanDeska
3.1 Introduction 115
3.2 FreeRadicalReactions 115
3.2.1 HydrogenAtomTransferReactions 116
3.2.2 FunctionalGroupTransformations 121
VIII Contents
3.3 RadicalAdditiontoImineDerivatives 124
3.3.1 GlyoxylateIminesasRadicalAcceptors 125
3.3.2 OximesandHydrazonesasRadicalAcceptors 126
3.3.3 NitronesasRadicalAcceptors 129
3.3.4 IsocyanatesasRadicalAcceptors 130
3.4 RadicalConjugateAddition 130
3.5 Conclusions 135
3.6 ExperimentalProtocols 135
3.6.1 Preparationof((1R,2S,5R)-5-methyl-2-(1-methyl-l-
phenylethyl)cyclohexyl2-[(tert-butoxycarbonyl)amino]-4-methyl-
pent-4-enoate)(7) 135
3.6.2 Synthesisof(2S)-3-{(1R,2S)-2-[(N-bis-Boc)amino]-1-cyclopropyl}-2-
benzyloxycarbonylamino-propionicAcidMethylEster(26) 136
3.6.3 Synthesisof(3aR,6S,7aS)-hexahydro-8,8-dimethyl-1-[(2R)-3,3-
dimethyl-1-oxo-2-(2,2-diphenylhydrazino)butyl]-3H-3a,6-methano-2,1-
benzisothiazole2,2-dioxide(42) 136
3.6.4 SynthesisofN-(2,6-diphenyl-methylpiperidine-2-
carboxamide(59) 137
3.6.5 SynthesisofMethyl2-(2-naphthylcarbonylamino)pentanoate
(80) 136
References 138
4 Synthesisofb-Lactams(Cephalosporins)byBioconversion 143
JoséLuisBarredo,MartaRodriguez-Sáiz,JoséLuisAdrio,
andArnoldL.Demain
4.1 Introduction 143
4.2 BiosyntheticPathwaysofCephalosporinsandPenicillins 146
4.3 Productionof7-ACAbyA.chrysogenum 147
4.4 Productionof7-ADCAbyA.chrysogenum 149
4.5 ProductionofPenicillinGbyA.chrysogenum 151
4.6 ProductionofCephalosporinsbyP.chrysogenum 152
4.7 ConversionofPenicillinGandotherPenicillinstoDAOG
byStreptomycesclavuligerus 153
4.7.1 ExpandaseProteinsandGenes 153
4.7.2 BioconversionofPenicillinGtoDAOG 155
4.7.3 BroadeningtheSubstrateSpecificityofExpandase 155
4.7.3.1 RestingCells 155
4.7.3.2 Cell-FreeExtracts 156
4.7.4 InactivationofExpandaseduringtheRing-ExpansionReaction 157
4.7.5 FurtherImprovementsintheBioconversionofPenicillin
GtoDAOG 158
4.7.5.1 StimulatoryEffectofGrowthinEthanol 158
4.7.5.2 UseofImmobilizedCells 159
4.7.5.3 EliminationofAgitationandAdditionofWater-Immiscible
Solvents 159
Contents IX
4.7.5.4 AdditionofCatalase 160
4.7.5.5 RecombinantS.clavuligerusExpandases 160
4.8 Conclusions 162
References 163
5 StructureandReactivityofb-Lactams 169
MichaelI.Page
5.1 Introduction 169
5.2 Structure 170
5.3 Reactivity 174
5.4 Hydrolysis 176
5.4.1 BaseHydrolysis 176
5.4.2 AcidHydrolysis 178
5.4.3 SpontaneousHydrolysis 180
5.4.4 Buffer-CatalyzedHydrolysis 180
5.4.5 MetalIon-CatalyzedHydrolysis 180
5.4.6 Micelle-CatalyzedHydrolysisofPenicillins 182
5.4.7 Cycloheptaamylose-CatalyzedHydrolysis 184
5.4.8 Enzyme-CatalyzedHydrolysis 185
5.4.8.1 Serineb-Lactamases 185
5.4.8.2 Metallob-Lactamases 187
5.5 Aminolysis 191
5.6 Epimerization 195
References 195
PartTwo AminoAcidCouplingChemistry 201
6 Solution-PhasePeptideSynthesis 203
YukoTsudaandYoshioOkada
6.1 PrincipleofPeptideSynthesis 203
6.2 ProtectionProcedures 205
6.2.1 AminoGroupProtection 205
6.2.1.1 ZGroup 205
6.2.1.2 SubstitutedZandotherUrethane-TypeProtectingGroups 207
6.2.1.3 BocGroup 207
6.2.1.4 TriGroup 208
6.2.1.5 FmocGroup 209
6.2.1.6 OtherRepresentativeProtectingGroups 211
6.2.2 CarboxylGroupProtection 212
6.2.2.1 MethylEster(-OMe)andEthylEster(-OEt) 213
6.2.2.2 BenzylEster(-OBzl) 213
6.2.2.3 tBuEster(-OtBu) 213
6.2.2.4 PhenacylEster(-OPac) 214
6.2.2.5 Hydrazides 214
6.2.3 Side-ChainProtection 215