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 FriendlyReactions fortheDesignofNovelProteins 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 ISBN:978-3-527-31867-4 TherapeuticRelevance 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 2007 ISBN:978-3-527-31603-8 Amino Acids, Peptides and Proteins in Organic Chemistry Volume 1 - Origins and Synthesis of Amino Acids Edited by Andrew B. Hughes TheEditor AllbookspublishedbyWiley-VCHarecarefully produced.Nevertheless,authors,editors,and Dr.AndrewB.Hughes publisherdonotwarranttheinformationcontained LaTrobeUniversity inthesebooks,includingthisbook,tobefreeof DepartmentofChemistry errors.Readersareadvisedtokeepinmindthat Victoria3086 statements,data,illustrations,proceduraldetailsor Australia otheritemsmayinadvertentlybeinaccurate. LibraryofCongressCardNo.: appliedfor BritishLibraryCataloguing-in-PublicationData Acataloguerecordforthisbookisavailablefromthe BritishLibrary. Bibliographicinformationpublishedby theDeutscheNationalbibliothek TheDeutscheNationalbibliothekliststhis publicationintheDeutscheNationalbibliografie; detailed bibliographicdataareavailableinthe Internetathttp://dnb.d-nb.de. #2009WILEY-VCHVerlagGmbH&Co.KGaA, Weinheim Allrightsreserved(includingthoseoftranslationinto otherlanguages).Nopartofthisbookmaybe reproducedinanyform–byphotoprinting, microfilm,oranyothermeans–nortransmittedor translatedintoamachinelanguagewithoutwritten permissionfromthepublishers.Registerednames, trademarks,etc.usedinthisbook,evenwhennot specificallymarkedassuch,arenottobeconsidered unprotectedbylaw. Composition ThomsonDigital,Noida,India Printing StraussGmbH,Mörlenbach Bookbinding Litges&DopfGmbH,Heppenheim CoverDesign SchulzGrafikDesign,Fußgönheim PrintedintheFederalRepublicofGermany Printedonacid-freepaper ISBN:978-3-527-32096-7 V Contents List of Contributors XVII PartOne OriginsofAminoAcids 1 1 ExtraterrestrialAminoAcids 3 Z.MartinsandM.A.Sephton 1.1 Introduction 3 1.2 ISM 6 1.2.1 FormationofAminoAcidsintheISMviaSolid-PhaseReactions 6 1.2.2 FormationofAminoAcidsintheISMviaGas-PhaseReactions 8 1.3 Comets 9 1.4 Meteorites 11 1.4.1 SourcesofMeteoriticAminoAcids(Extraterrestrialversus TerrestrialContamination) 17 1.4.1.1 DetectionofAminoAcidsthatareUnusualintheTerrestrial Environment 17 1.4.1.2 DeterminationoftheAminoAcidContentoftheMeteoriteFall Environment 17 1.4.1.3 DeterminationofEnantiomericRatios 18 1.4.1.4 DeterminationofCompound-SpecificStableIsotopeRatios ofHydrogen,Carbon,andNitrogen 18 1.4.2 SynthesisofMeteoriticAminoAcids 19 1.5 MicrometeoritesandIDPs 23 1.6 Mars 23 1.7 DeliveryofExtraterrestrialAminoAcidtotheEarthandits ImportancetotheOriginofLife 24 1.8 Conclusions 26 References 27 2 ‘‘Terrestrial’’AminoAcidsandtheirEvolution 43 StephenFreeland 2.1 Introduction 43 AminoAcids,PeptidesandProteinsinOrganicChemistry.Vol.1–OriginsandSynthesisofAminoAcids. EditedbyAndrewB.Hughes Copyright(cid:1)2009WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim ISBN:978-3-527-32096-7 VI Contents 2.2 Whatarethe20‘‘Terrestrial’’AminoAcids? 44 2.2.1 The21stand22ndGeneticallyEncodedAminoAcids 45 2.2.2 DootherGeneticallyEncodedAminoAcidsAwaitDiscovery? 46 2.2.3 GeneticEngineeringcanEnlargetheAminoAcidAlphabet 47 2.2.4 SignificanceofUnderstandingtheOriginsofthe StandardAlphabet 48 2.3 WhatdoWeKnowabouttheEvolutionoftheStandardAmino AcidAlphabet? 49 2.3.1 Nonbiological,NaturalSynthesisofAminoAcids 50 2.3.2 BiosyntheticTheoriesfortheEvolutionaryExpansionofthe StandardAminoAcidAlphabet 53 2.3.3 EvidenceforaSmallerInitialAminoAcidAlphabet 55 2.3.4 ProteinsasEmergentProductsofanRNAWorld 56 2.3.5 StereochemicalRationaleforAminoAcidSelection 57 2.4 AminoAcidsthatLifePassedOver:ARolefor NaturalSelection? 58 2.4.1 WeretheStandardAminoAcidsChosenforHigh BiochemicalDiversity? 60 2.4.2 WeretheStandardAminoAcidsChosenfor‘‘Cheap’’ Biosynthesis? 62 2.4.3 WeretheStandardAminoAcidsChosentoSpeedUpEvolution? 62 2.5 WhyDoesLifeGeneticallyEncodeL-AminoAcids? 64 2.6 Summary,Synthesis,andConclusions 64 References 66 PartTwo Production/SynthesisofAminoAcids 77 3 UseofEnzymesintheSynthesisofAminoAcids 79 TheoSonke,BernardKaptein,andHansE.Schoemaker 3.1 Introduction 79 3.2 Chemo-EnzymaticProcessestoEnantiomericallyPure AminoAcids 80 3.3 AcylaseProcess 81 3.4 AmidaseProcess 83 3.4.1 AmidaseProcessfora,a-Disubstituteda-AminoAcids 86 3.5 HydantoinaseProcess 88 3.6 AmmoniaLyaseProcesses 90 3.6.1 Aspartase-CatalyzedProductionofL-AsparticAcid 91 3.6.2 ProductionofL-AlaninefromFumaricAcidby anAspartase–DecarboxylaseCascade 92 3.6.3 PhenylalanineAmmoniaLyase-CatalyzedProductionof L-PhenylalanineandDerivatives 93 3.7 AminotransferaseProcess 94 3.7.1 Aminotransferase-CatalyzedProductionofD-a-H-a-AminoAcids 97 Contents VII 3.8 AADHProcess 99 3.9 Conclusions 102 References 103 4 b-AminoAcidBiosynthesis 119 PeterSpiteller 4.1 Introduction 119 4.1.1 Importanceofb-AminoAcidsandtheirBiosynthesis 119 4.1.2 ScopeofthisChapter 119 4.2 Biosynthesisofb-AminoAcids 120 4.2.1 Biosynthesisofb-Alanineandb-AminoisobutyricAcid 120 4.2.1.1 b-Alanine 120 4.2.1.2 b-AminoisobutyricAcid 122 4.2.2 Biosynthesisofb-AminoAcidsby2,3-Aminomutasesfrom a-AminoAcids 122 4.2.2.1 b-Lysine,b-Arginine,andRelatedb-AminoAcids 124 4.2.2.2 b-Phenylalanine,b-Tyrosine,andRelatedb-AminoAcids 127 4.2.2.3 b-Glutamateandb-Glutamine 132 4.2.2.4 b-Leucine 132 4.2.2.5 b-Alanine 132 4.2.3 Biosynthesisofa,b-DiaminoAcidsfroma-AminoAcids 132 4.2.3.1 GeneralBiosynthesisofa,b-DiaminoAcids 132 4.2.3.2 StructuresandOccurrenceofa,b-DiaminoAcidsinNature 132 4.2.3.3 BiosynthesisofSelecteda,b-DiaminoAcids 135 4.2.3.3.1 Biosynthesisofb-ODAP 135 4.2.3.3.2 Biosynthesisofthea,b-DiaminopropanoicAcidMoietyinthe Bleomycins 136 4.2.3.3.3 BiosynthesisofthePenicillins 137 4.2.3.3.4 BiosynthesisoftheCapreomycidineMoietyinViomycine 137 4.2.3.3.5 BiosynthesisoftheStreptolidineMoietyinStreptothricinF 137 4.2.4 Biosynthesisofa-Keto-b-AminoAcidsfroma-AminoAcids 139 4.2.5 DeNovoBiosynthesisofb-AminoAcidsbyPKSs 139 4.2.5.1 Introduction 139 4.2.5.2 GeneralBiosynthesisofPolyketide-Typeb-AminoAcids 141 4.2.5.3 StructuresandOccurrenceofPolyketide-Typeb-AminoAcids inNature 142 4.2.5.4 BiosynthesisofSelectedPolyketide-Typeb-AminoAcids 149 4.2.5.4.1 Long-Chainb-AminoAcidsOccurringasConstituentsof theIturins 149 4.2.5.4.2 BiosynthesisoftheAhdaMoietyinMicroginin 151 4.2.5.4.3 BiosynthesisoftheAhpaResidueinBestatin 151 4.2.5.4.4 BiosynthesisoftheAddaResidueintheMicrocystins 152 4.2.6 b-AminoAcidsWhoseBiosynthesisisStillUnknown 152 4.3 ConclusionsandFutureProspects 154 References 155 VIII Contents 5 MethodsfortheChemicalSynthesisofNoncodeda-Amino AcidsfoundinNaturalProductPeptides 163 StephenA.Habay,SteveS.Park,StevenM.Kennedy, andA.RichardChamberlin 5.1 Introduction 163 5.2 NoncodedCAAs 164 5.3 NoncodedAminoAcidsbyChemicalModificationofCoded AminoAcids 185 5.4 NoncodedAminoAcidswithElaborateSide-Chains 205 5.5 Conclusions 226 References 226 6 SynthesisofN-AlkylAminoAcids 245 LuigiAurelioandAndrewB.Hughes 6.1 Introduction 245 6.2 N-MethylationviaAlkylation 246 6.2.1 S 2Substitutionofa-BromoAcids 246 N 6.2.2 N-MethylationofSulfonamides,Carbamates,andAmides 249 6.2.2.1 Base-MediatedAlkylationofN-TosylSulfonamides 249 6.2.2.2 BaseMediatedAlkylationofN-Nitrobenzenesulfonamides 250 6.2.2.3 N-MethylationviaSilverOxide/MethylIodide 252 6.2.2.4 N-MethylationviaSodiumHydride/MethylIodide 253 6.2.2.5 N-MethylationofTrifluoroacetamides 257 6.2.2.6 N-MethylationviatheMitsunobuReaction 257 6.3 N-MethylationviaSchiff’sBaseReduction 259 6.3.1 ReductionofSchiff’sBasesviaTransition Metal-MediatedReactions 259 6.3.2 ReductionofSchiff’sBasesviaFormicAcid:TheLeuckart Reaction 260 6.3.3 QuaternizationofIminoSpecies 261 6.3.4 ReductionofSchiff’sBasesviaBorohydrides 263 6.3.5 BoraneReductionofAmides 264 6.4 N-MethylationbyNovelMethods 265 6.4.1 1,3-Oxazolidin-5-ones 265 6.4.2 AsymmetricSyntheses 272 6.4.3 RacemicSyntheses 277 6.5 N-AlkylationofAminoAcids 280 6.5.1 BorohydrideReductionofSchiff’sBases 280 6.5.1.1 SodiumBorohydrideReductions 281 6.5.1.2 SodiumCyanoborohydrideReductions 281 6.5.1.3 SodiumTriacetoxyborohydrideReductions 282 6.5.2 N-AlkylationofSulfonamides 282 6.5.2.1 Base-MediatedAlkylationofBenzeneSulfonamides 282 6.5.3 ReductionofN-AcylAminoAcids 283 6.5.3.1 ReductionofAcetamides 284 Contents IX 6.5.4 NovelMethodsforN-Alkylatinga-AminoAcids 284 6.5.4.1 AsymmetricSynthesisofN-Alkyla-AminoAcids 284 6.5.4.2 N-Alkylationof1,3-Oxazolidin-5-ones 284 References 286 7 RecentDevelopmentsintheSynthesisofb-AminoAcids 291 YamirBandalaandEusebioJuaristi 7.1 Introduction 291 7.2 Synthesisofb-AminoAcidsbyHomologationofa-AminoAcids 291 7.3 ChiralPool:EnantioselectiveSynthesisofb-AminoAcidsfrom AsparticAcid,Asparagine,andDerivatives 298 7.4 Synthesisofb-AminoAcidsbyConjugateAdditionofNitrogen NucleophilestoEnones 300 7.4.1 Achiralb-AminoAcids 300 7.4.2 EnantioselectiveApproaches 304 7.4.2.1 Additionof‘‘ChiralAmmonia’’EquivalentstoConjugated ProchiralAcceptors 304 7.4.2.2 AdditionofaNitrogenNucleophiletoaChiralAcceptor 306 7.4.2.3 AsymmetricCatalysis 308 7.5 Synthesisofb-AminoAcidsvia1,3-DipolarCycloaddition 312 7.6 Synthesisofb-AminoAcidsbyNucleophilicAdditions 316 7.6.1 Aldol-andMannich-TypeReactions 316 7.6.2 Morita–Baylis–Hillman-TypeReactions 321 7.6.3 Mannich-TypeReactions 324 7.7 Synthesisofb-AminoAcidsbyDiverseAdditionor SubstitutionReactions 328 7.8 Synthesisofb-AminoAcidsbyStereoselectiveHydrogenation ofProchiral3-AminoacrylatesandDerivatives 330 7.8.1 ReductionsInvolvingPhosphorus-MetalComplexes 331 7.8.2 ReductionsInvolvingCatalyticHydrogenations 333 7.9 Synthesisofb-AminoAcidsbyuseofChiralAuxiliaries: StereoselectiveAlkylation 334 7.10 Synthesisofb-AminoAcidsviaRadicalReactions 338 7.11 MiscellaneousMethodsfortheSynthesisofb-AminoAcids 340 7.12 Conclusions 347 7.13 ExperimentalProcedures 348 7.13.1 RepresentativeExperimentalProcedure:Synthesisof(S)- 3-(tert-Butyloxycarbonylamino)-4-phenylbutanoicAcid 348 7.13.2 RepresentativeExperimentalProcedure:Synthesisof (S)-2-(Aminomethyl)-4-phenylbutanoicAcid,(S)-19 350 7.13.3 RepresentativeExperimentalProcedure:Synthesisofb3-AminoAcids byConjugateAdditionofHomochiralLithiumN-Benzyl-N- (a-methylbenzyl)amide 352 7.13.4 RepresentativeExperimentalProcedure:SynthesisofCyclicand Acyclicb-AminoAcidDerivativesby1,3-DipolarCycloaddition 353