教學課件columbia大學有機化學課件27_04_06 html

1、27.4Synthesis of Amino AcidsOOH2OCH CHCO+2NHCH CHCOHNH Br3334+NH3(65-70%)BrFrom a-Halo Carboxylic AcidsONH4ClNaCNCH CHCH CHCN33NH21.2.H2O, HCl, heatHOOCH3CHCO(52-60%)+NH3Strecker SynthesisUsing Diethyl AcetamidomalonateOOCCCOCH2CH3CH3CH2OCH3CNHHOCan be used in the same manner as diethyl malonate (Se

2、ction 21.7).OOCH3CH2OCCCOCH2CH3HCH3CNHO1. NaOCH2CH32.C6H5CH2ClOOCH3CH2OCCCOCH2CH3(90%)CH2C6H5CH3CNHOExampleOOHOCCCOHCH2C6H5H3N+HBr, H2O, heatOOCH3CH2OCCCOCH2CH3CH2C6H5CH3CNHOExampleO(65%)HCCOHCH2C6H5H3N+HBr, H2O, heatOOCH3CH2OCCCOCH2CH3CH2C6H5CH3CNHOExample27.5Reactions of Amino AcidsThe amino nitro

3、gen of an amino acid can be converted to an amide with the customary acylating agents.OOO+H3NCH2COCH3COCCH3OO(89-92%)CH3CNHCH2COHAcylation of Amino GroupThe carboxyl group of an amino acid can beconverted to an ester.The following illustratesFischer esterification of alanine.O+H3NCHCOCH3CH2OHCH3HClO

4、+ClH3NCHCOCH2CH3(90-95%)CH3Esterification of Carboxyl GroupAmino acids are detected by the formation of a purple color on treatment with ninhydrin.OO+OHOH+H3NCHCOROORCH + CO2 + H2O +OONOONinhydrin Test27.6Some Biochemical Reactions of Amino AcidsO+NH3HO2CCH2CH2CCO2Henzymes and reducing coenzymes2HO

5、CCH CH CHCO222+ NH3This reaction is the biochemical analog of reductive amination (Section 22.11).Biosynthesis olutamic AcidO2+HO CCH CH CHCOCH CCO H22232+ NH3L-Glutamic acid acts as a source of the amine group in the biochemical conversion of a-ketoacids to other amino acids.In the exampleshown, py

6、ruvic acid is converted to L-alanine.Transamination via L-Glutamic AcidO2+HO CCH CH CHCOCH CCO H22232+ NH3enzymesOCH CHCO +HO CCH CH CCO H322222+ NH3Transamination via L-Glutamic AcidO2HO CCH CH CHCO+CH CCO H22232+ NH3The first step is imine formation between theamino group o acid.lutamic acid and p

7、yruvicMechanismO2HO CCH CH CHCO+CH CCO H22232+ NH3HO CCH CHCHCO2222NCH CCO32MechanismFormation of the imine is followed by proton removal at one carbon and protonation of another carbon.H2HO CCH CH CCO222NCH CCO32HO2CCH2CH2CCO2NCH CCO32HH2HO CCH CH CCO222NCH CCO32HO CCH CH CCO2222NCH CCO32HHydrolysi

8、s of the imine function givesa-keto glutarate and L-alanine.HO CCH CH CCO2222NCH CCO32HH2O+NH3HO CCH CH CCO CH CCO +222232OHL-Tyrosine is biosynthesized from L-phenylalanine. A key step is epoxidation of the aromatic ring to give an arene oxide intermediate.CH CHCO 22+ NH3Biosynthesis of L-TyrosineC

9、H CHCO 22+ NH3O2, enzymeCH CHCO 22+ NH3OBiosynthesis of L-TyrosineCH CHCO 22+ NH3enzymeCH CHCO HO22+ NH3OBiosynthesis of L-TyrosineConversion to L-tyrosine is one of the major metabolic pathways of L-phenylalanine.Individuals who lack the enzymes necessary to convert L-phenylalanine to L-tyrosine ca

10、n sufferfrom PKU disease.In PKU disease, L-phenylalanine is diverted to a pathway leading to phenylpyruvic acid, which is toxic.Newborns are routinely tested for PKU disease. Treatment consists of reducing their dietary intake of phenylalanine-rich proteins.Biosynthesis of L-TyrosineDecarboxylation

11、is a common reaction of a-amino acids.An example is the conversion ofL-histidine to histamine.Antihistamines act byblocking the action of histamine.NCH2CHCO2N+ NHH3DecarboxylationNCH2CH2 NH2NHCO2, enzymesNCH2CHCO2N+ NHH3DecarboxylationCO The chemistry of the brain and central nervous system is affec

12、ted by neurotransmitters.Several important neurotransmitters are biosynthesized from L-tyrosine.+ H3NHHHOHL-Tyrosine2NeurotransmittersCO The common name of this compound isHHHL-DOPA.It occursnaturally in thebrain.It is widelyprescribed to reduce the symptoms of Parkinsonism.HOOHL-3,4-Dihydroxyphenylalanine2+