Amino Acids, Peptides and Proteins in Organic Chemistry 2: Modified Amino Acids, Organocatalysis and Enzymes (Amino Acids, Peptides and Proteins in Organic Chemistry (VCH))

695 Pages·2009·6.63 MB·English

by  Andrew B. Hughes

Amino Acids, Peptides and Proteins
in Organic Chemistry
Edited by
Andrew B. Hughes
Further Reading
Fessner,W.-D.,Anthonsen, T. Budisa, N.
Modern Biocatalysis Engineering the Genetic Code
StereoselectiveandEnvironmentally ExpandingtheAminoAcidRepertoire
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2009 2006
ISBN:978-3-527-32071-4 ISBN:978-3-527-31243-6
Sewald, N., Jakubke,H.-D. Demchenko, A.V. (ed.)
Peptides: Chemistry and Handbook of Chemical
Biology Glycosylation
2009 AdvancesinStereoselectivityand
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2008
Lutz, S., Bornscheuer,U. T. (eds.)
ISBN:978-3-527-31780-6
Protein Engineering
Lindhorst, T. K.
Handbook
Essentials of Carbohydrate
2VolumeSet
Chemistry and Biochemistry
2009
ISBN:978-3-527-31850-6 2007
ISBN:978-3-527-31528-4
Aehle, W.(ed.)
Enzymes in Industry
ProductionandApplications
2007
ISBN:978-3-527-31689-2
Wiley-VCH (ed.)
Ullmann’s Biotechnology and
Biochemical Engineering
2VolumeSet
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ISBN:978-3-527-31603-8
Amino Acids, Peptides and Proteins
in Organic Chemistry
Volume 2 - Modified Amino Acids, Organocatalysis
and Enzymes
Edited by
Andrew B. Hughes
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#2009WILEY-VCHVerlagGmbH&Co.KGaA,
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ISBN:978-3-527-32098-1
V
Contents
List of Contributors XIX
PartOne SynthesisandChemistryofModifiedAminoAcids 1
1 SynthesisandChemistryofa,b-DidehydroaminoAcids 3
UliKazmaier
1.1 Introduction 3
1.2 SynthesisofDDAAs 3
1.2.1 DDAAsviaEliminations 3
1.2.1.1 DDAAsviab-Elimination 3
1.2.1.1.1 Fromb-HydroxyAminoAcids 3
1.2.1.1.2 Fromb-Thio-andSelenoaminoAcids 5
1.2.1.2 EliminationfromN-Hydroxylatedand-ChlorinatedAminoAcids
andPeptides 6
1.2.1.3 DDAAsfroma-OxoAcidsandAmides 6
1.2.1.4 DDAAsfromAzides 7
1.2.2 DDAAsviaC¼CBondFormation 7
1.2.2.1 DDAAsviaAzlactones[5(4H)-Oxazolones] 7
1.2.2.2 DDAAsviaHorner–EmmonsandWittigReactions 8
1.2.2.3 DDAAsviaEnolatesofNitro-andIsocyano-andIminoacetates 10
1.2.3 DDAAsviaC–CBondFormation 12
1.2.3.1 DDAAsviaHeckReaction 12
1.2.3.2 DDAAsviaCross-CouplingReactions 13
1.3 ReactionsofDDAAs 14
1.3.1 AdditionstotheC¼CBond 14
1.3.1.1 NucleophilicAdditions 14
1.3.1.2 RadicalAdditions 15
1.3.1.3 Cycloadditions 17
1.3.1.3.1 [3þ2]Cycloadditions 18
AminoAcids,PeptidesandProteinsinOrganicChemistry.
Vol.2–ModifiedAminoAcids,OrganocatalysisandEnzymes.EditedbyAndrewB.Hughes
Copyright(cid:1)2009WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-32098-1
VI Contents
1.3.1.3.2 [4þ2]Cycloadditions 19
1.3.1.4 CatalyticHydrogenations 19
1.3.2 HalogenationsofDDAAs 21
1.4 Conclusions 21
1.5 ExperimentalProcedures 22
1.5.1 General Procedure for the Two-Step Synthesis of Dehydroisoleucine
Derivatives 22
1.5.2 GeneralProcedurefortheSynthesisofa,b-DidehydroaminoAcidEsters
bythePhosphorylglycineEsterMethodusingDBU 22
1.5.3 GeneralProcedurefortheSynthesisofa-ChloroglycineDerivatives 23
1.5.4 GeneralProcedurefortheSynthesisofHomomericDimers 23
1.5.5 GeneralProcedurefortheSynthesisof(Z)-g-Alkyl-a,
b-DidehydroglutamatesfromIminoGlycinates 24
1.5.6 Palladium-CatalyzedTrifoldHeckCoupling 25
1.5.7 GeneralExperimentalProcedureforConjugateAdditionofAlkyl
iodidestoChirala,b-UnsaturatedAminoAcidDerivatives 25
1.5.8 BrominationofN-tert-ButyloxycarbonyldehydroaminoAcids 26
References 26
2 SynthesisandChemistryofa-HydrazinoAcids 35
JoëlleVidal
2.1 Introduction 35
2.1.1 a-HydrazinoAcidsarePotentInhibitorsofPyridoxal
PhosphateEnzymes 35
2.1.2 NaturalProductsContainingtheN–N–C–C¼OFragment 36
2.1.3 SyntheticBioactiveProductsContainingtheN–N–C–C¼O
Fragment 39
2.1.4 TheCO–N–N–C–CO–NHFragmentisaTurnInducerin
Pseudopeptides 40
2.2 Synthesis 41
2.2.1 Disconnection1a:ReactionofHydrazineDerivativeswith
CarbonElectrophiles 41
2.2.1.1 ReactionofHydrazineDerivativeswithEnantiopure
a-HalogenoAcids 42
2.2.1.2 ReactionofHydrazineDerivativeswithEnantiopureActivated
a-HydroxyEsters 42
2.2.1.3 MitsunobuReactionofAminophthalimideDerivativeswith
Enantiopurea-HydroxyEsters 43
2.2.1.4 ReactionofHydrazineDerivativeswithNonracemicEpoxides 43
2.2.1.5 EnantioselectiveConjugateAdditionofHydrazinesto
a,b-UnsaturatedImides 44
2.2.2 Disconnection1b:StereoselectiveSynthesisusing
Azodicarboxylates 44
2.2.2.1 Stereoselectivea-HydrazinationofChiralCarbonylCompounds
usingAzodicarboxylates 45
Contents VII
2.2.2.2 CatalyticEnantioselectivea-HydrazinationofCarbonylCompounds
usingAzodicarboxylates 46
2.2.2.3 Stereoselectivea-HydrazinationofChirala,b-Unsaturated
CarboxylatesusingAzodicarboxylates 50
2.2.3 Disconnection2:SynthesisfromChiralNonracemica-Amino
Acids 52
2.2.3.1 SchestakowRearrangementofHydantoicAcidsPreparedfrom
a-AminoAcids 52
2.2.3.2 ReductionofN-Nitroso-a-AminoEsters 52
2.2.3.3 Aminationofa-AminoAcidsbyHydroxylamineDerivatives 52
2.2.3.4 Aminationofa-AminoAcidsbyOxaziridines 53
2.2.4 Disconnections3,4,and5:SynthesesfromHydrazonesor
a-Diazoesters 55
2.2.4.1 CatalyticEnantioselectiveHydrogenationofHydrazones 56
2.2.4.2 StereoselectiveandCatalyticEnantioselective
StreckerReaction 56
2.2.4.3 StereoselectiveAdditionofOrganometallicReagentsto
Hydrazones 57
2.2.4.4 StereoselectiveorCatalyticEnantioselectiveMannich-Type
ReactionwithHydrazones 58
2.2.4.5 EnantioselectiveFriedel–CraftsAlkylationswithHydrazones 59
2.2.4.6 DiastereoselectiveZinc-MediatedCarbonRadicalAddition
toHydrazones 59
2.2.4.7 CatalyticEnantioselectiveReactionofa-DiazoesterswithAldehydes
andSubsequentStereoselectiveReduction 59
2.2.5 PiperazicAcidandDerivativesbyCycloadditionReactions 61
2.2.5.1 Diels–AlderCycloaddition 61
2.2.5.2 1,3-DipolarCycloaddition 62
2.3 Chemistry 63
2.3.1 CleavageoftheN–NBond 63
2.3.2 ReactivityoftheHydrazinoFunction 67
2.3.2.1 ReactionofUnprotecteda-HydrazinoAcidDerivativeswith
AcylatingReagents 67
2.3.2.2 ReactionofN1-Substituteda-HydrazinoAcidDerivativeswith
AcylatingReagents 69
2.3.2.3 ReactionofN2-Protecteda-HydrazinoAcidDerivativeswith
AcylatingReagents 69
2.3.2.4 ReactionwithAldehydesandKetones 69
2.3.3 ReactivityoftheCarboxylFunction 73
2.3.4 SynthesisofHeterocycles 74
2.3.4.1 CyclizationLeadingtoPiperazicAcidDerivatives 74
2.3.4.2 OtherHeterocycles 75
2.4 Conclusions 78
2.5 ExperimentalProcedures 79
2.5.1 (S)-2-hydrazinosuccinicAcidMonohydrate 79
VIII Contents
2.5.2 ((cid:1))-(R)-N1,N2-dibenzyloxycarbonyl-2-hydrazino-2-phenylPropionic
Acid,MethylEster 80
2.5.3 (þ)-(R)-N1,N2-Bis(benzyloxycarbonyl)-1-hydrazino-2-oxocyclopentane
CarboxylicAcid,EthylEster 81
2.5.4 ((cid:1))-L-N-Aminovaline 81
2.5.5 (þ)-L-N-benzyl-N-(tert-butoxycarbonylamino)tryptophan,
HexylamineSalt 82
2.5.6 (R)-2-(N2-benzoylhydrazino)-2-(4-dimethylaminophenyl)
Acetonitrile 83
2.5.7 tert-Butoxycarbonylamino-(4-dimethylamino-2-methoxy-phenyl)-acetic
AcidEthylEsterbyReductionusingSmI 84
2
2.5.8 (R)-1,2-bis(benzyloxycarbonyl)piperazine-3-carboxylicAcid 84
References 86
3 HydroxamicAcids:Chemistry,Bioactivity,andSolution-
andSolid-PhaseSynthesis 93
DarrenGriffith,MarcDevocelle,andCelineJ.Marmion
3.1 Introduction 93
3.2 Chemistry,Bioactivity,andClinicalUtility 93
3.2.1 Chemistry 93
3.2.2 BioactivityandClinicalUtility 95
3.2.2.1 HydroxamicAcidsasSiderophores 95
3.2.2.2 HydroxamicAcidsasEnzymeInhibitors 97
3.2.2.2.1 MMPInhibitors 98
3.2.2.2.2 HDACInhibitors 102
3.2.2.2.3 PGHSInhibitors 104
3.3 Solution-PhaseSynthesisofHydroxamicAcids 106
3.3.1 SynthesisofHydroxamicAcidsDerivedfromCarboxylic
AcidDerivatives 106
3.3.1.1 FromEsters 107
3.3.1.2 FromAcidHalides 108
3.3.1.3 FromAnhydrides 109
3.3.1.4 From[1.3.5]Triazine-CoupledCarboxylicAcids 110
3.3.1.5 FromCarbodiimide-CoupledCarboxylicAcids 111
3.3.1.6 FromAcyloxyphosphoniumIons 111
3.3.1.7 FromCarboxylicAcidsCoupledwithotherAgents 113
3.3.2 SynthesisofHydroxamicAcidsfromN-acyloxazolidinones 114
3.3.3 SynthesisofHydroxamicAcidsfromgem-Dicyanoepoxides 115
3.3.4 SynthesisofHydroxamicAcidsfromAldehydes 115
3.3.5 SynthesisofHydroxamicAcidsfromNitroCompounds 116
3.3.6 SynthesisofHydroxamicAcidsviaaPalladium-Catalyzed
CascadeReaction 116
3.3.7 SynthesisofN-Formylhydroxylamine(FormohydroxamicAcid) 117
3.3.8 SynthesisofReverseorRetro-Hydroxamates 117
3.3.9 SynthesisofAcylhydroxamicAcids 120
Contents IX
3.4 Solid-PhaseSynthesisofHydroxamicAcids 121
3.4.1 AcidicCleavage 122
3.4.1.1 O-TetheredHydroxylamine 122
3.4.1.1.1 Cleavagewith30–90%TFA 122
3.4.1.1.2 SuperAcid-SensitiveLinkers 124
3.4.1.2 N-TetheredHydroxylamine 126
3.4.1.3 OtherMethodsofSolid-PhaseSynthesisofHydroxamicAcids
basedonanAcidicCleavage 126
3.4.2 NucleophilicCleavage 128
3.4.2.1 OtherMethods 129
3.5 Conclusions 130
3.6 ExperimentalProcedures 130
3.6.1 Synthesisof3-PyridinehydroxamicAcid 130
3.6.2 SynthesisofO-benzylbenzohydroxamicAcid 131
3.6.3 SynthesisofN-methylbenzohydroxamicAcid 131
3.6.4 SynthesisofIsobutyrohydroxamicAcid 132
3.6.5 SynthesisofO-benzyl-2-phenylpropionohydroxamicAcid 132
3.6.6 SynthesisofMethyl3-(2-quinolinylmethoxy)benzeneacetohydroxamic
Acid 133
3.6.7 SynthesisoftheChlamydocinHydroxamicAcidAnalog,
cyclo(L-Asu(NHOH)–Aib-L-Phe–D-Pro) 133
3.6.8 SynthesisofO-benzyl-4-methoxybenzohydroxamicAcid 134
3.6.9 SynthesisofO-benzylbenzohydroxamicacid 134
3.6.10 Synthesisofa4-chlorophenylSubstituted-a-bromohydroxamic
acid 134
3.6.11 Synthesisof4-ChlorobenzohydroxamicAcid 135
3.6.12 SynthesisofAcetohydroxamicAcid 135
3.6.13 SynthesisofN-hydroxyLactam 136
3.6.14 SynthesisofO-tert-butyl-N-formylhydroxylamine 136
3.6.15 SynthesisofTriacetylsalicylhydroxamicAcid 137
References 137
4 Chemistryofa-AminoboronicAcidsandtheirDerivatives 145
ValeryM.DembitskyandMorrisSrebnik
4.1 Introduction 145
4.2 Synthesisofa-AminoboronicAcids 146
4.3 Synthesisofa-AmidoboronicAcidDerivatives 146
4.4 AsymmetricSynthesisviaa-HaloalkylboronicEsters 151
4.5 SynthesisofGlycinea-AminoboronicAcids 154
4.6 SynthesisofProlinea-AminoboronicAcids 155
4.7 SynthesisofAlaninea-AminoboronicAcids 162
4.8 SynthesisofOrnithinea-AminoboronicAcids 164
4.9 SynthesisofArgininea-AminoboronicAcids 167
4.10 SynthesisofPhenethylPeptideBoronicAcids 170
4.11 SynthesisviaZirconoceneSpecies 172