27.4 Synthesis of Amino Acids

From  -Halo Carboxylic Acids CH 3 CHCOH BrO 2NH32NH32NH32NH3 + H2OH2OH2OH2O CH 3 CHCO NH3NH3NH3NH3O+ – (65-70%) + NH 4 Br

Strecker Synthesis NH 4 Cl NaCN CH 3 CHCO NH3NH3NH3NH3O+ – (52-60%) CH 3 CH O 1. H 2 O, HCl, heat 2. HO – CH 3 CHC NH2NH2NH2NH2N

Using Diethyl Acetamidomalonate C C C OCH 2 CH 3 HOO CH 3 CH 2 O CH 3 CNH O Can be used in the same manner as diethyl malonate (Section 21.7).

Example 1. NaOCH 2 CH 3 2. C 6 H 5 CH 2 Cl OO CH 3 CH 2 OCCCOCH 2 CH 3 H CH 3 CNH O OO CH 3 CH 2 OCCCOCH 2 CH 3 CH 2 C 6 H 5 CH 3 CNH O (90%)

ExampleOO CH 3 CH 2 OCCCOCH 2 CH 3 CH 2 C 6 H 5 CH 3 CNH O HBr, H 2 O, heat O O HOCCCOH CH 2 C 6 H 5 H3NH3NH3NH3N +

ExampleOO CH 3 CH 2 OCCCOCH 2 CH 3 CH 2 C 6 H 5 CH 3 CNH O HBr, H 2 O, heat O HCCOH CH 2 C 6 H 5 H3NH3NH3NH3N + (65%)

27.5 Reactions of Amino Acids

Acylation of Amino Group The amino nitrogen of an amino acid can be converted to an amide with the customary acylating agents. O H 3 NCH 2 CO –++ CH 3 COCCH 3 OO CH 3 CNHCH 2 COH OO(89-92%)

Esterification of Carboxyl Group The carboxyl group of an amino acid can be converted to an ester. The following illustrates Fischer esterification of alanine. + CH 3 CH 2 OH (90-95%) HClO H 3 NCHCO – + CH 3 O H 3 NCHCOCH 2 CH 3 + CH 3 –Cl

Ninhydrin Test Amino acids are detected by the formation of a purple color on treatment with ninhydrin. OHOO OH +O H 3 NCHCO – + R O O O N O– ORCH + CO 2 + H2OH2OH2OH2O +

27.6 Some Biochemical Reactions of Amino Acids

Biosynthesis of L -Glutamic Acid This reaction is the biochemical analog of reductive amination (Section 22.11). HO 2 CCH 2 CH 2 CCO 2 H O NH3NH3NH3NH3 + enzymes and reducing coenzymes HO 2 CCH 2 CH 2 CHCO 2 – NH3NH3NH3NH3 +

Transamination via L -Glutamic Acid L -Glutamic acid acts as a source of the amine group in the biochemical conversion of  -keto acids to other amino acids. In the example shown, pyruvic acid is converted to L -alanine. HO 2 CCH 2 CH 2 CHCO 2 – NH3NH3NH3NH3 + + CH 3 CCO 2 H O

Transamination via L -Glutamic Acid HO 2 CCH 2 CH 2 CHCO 2 – NH3NH3NH3NH3 + + CH 3 CCO 2 H Oenzymes HO 2 CCH 2 CH 2 CCO 2 H O+ CH 3 CHCO 2 – NH3NH3NH3NH3 +

Mechanism HO 2 CCH 2 CH 2 CHCO 2 – NH3NH3NH3NH3 + + CH 3 CCO 2 H O The first step is imine formation between the amino group of L -glutamic acid and pyruvic acid.

Mechanism HO 2 CCH 2 CH 2 CHCO 2 – NH3NH3NH3NH3 + + CH 3 CCO 2 H O CH 3 CCO 2 – HO 2 CCH 2 CH 2 CHCO 2 N –

CH 3 CCO 2 – HO 2 CCH 2 CH 2 CCO 2 N–H Formation of the imine is followed by proton removal at one carbon and protonation of another carbon.

CH 3 CCO 2 – HO 2 CCH 2 CH 2 CCO 2 N–H CH 3 CCO 2 – HO 2 CCH 2 CH 2 CCO 2 N H

– CH 3 CCO 2 – HO 2 CCH 2 CH 2 CCO 2 N H Hydrolysis of the imine function gives  -keto glutarate and L -alanine.

– CH 3 CCO 2 – HO 2 CCH 2 CH 2 CCO 2 N H O– CH 3 CCO 2 – NH3NH3NH3NH3 H++ H2OH2OH2OH2O

L -Tyrosine is biosynthesized from L -phenylalanine. A key step is epoxidation of the aromatic ring to give an arene oxide intermediate. Biosynthesis of L -Tyrosine CH 2 CHCO 2 – NH3NH3NH3NH3 +

Biosynthesis of L -Tyrosine CH 2 CHCO 2 – NH3NH3NH3NH3 + – NH3NH3NH3NH3 + O O 2, enzyme

Biosynthesis of L -Tyrosine CH 2 CHCO 2 – NH3NH3NH3NH3 + O enzyme – NH3NH3NH3NH3 + HOHOHOHO

Biosynthesis of L -Tyrosine Conversion 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 can suffer from 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.

Decarboxylation Decarboxylation is a common reaction of  - amino acids. An example is the conversion of L -histidine to histamine. Antihistamines act by blocking the action of histamine. CH 2 CHCO 2 – NH3NH3NH3NH3 + NHNHNHNH N

Decarboxylation – NH3NH3NH3NH3 + NHNHNHNH N –CO 2, enzymes CH 2 CH 2 NH 2 NHNHNHNH N

Neurotransmitters The chemistry of the brain and central nervous system is affected by neurotransmitters. Several important neurotransmitters are biosynthesized from L -tyrosine. OHOHOHOH CO 2 –H H H H3NH3NH3NH3N + L -Tyrosine

Neurotransmitters The common name of this compound is L -DOPA. It occurs naturally in the brain. It is widely prescribed to reduce the symptoms of Parkinsonism. OHOHOHOH CO 2 – H H H H3NH3NH3NH3N + L -3,4-Dihydroxyphenylalanine HOHOHOHO

Neurotransmitters Dopamine is formed by decarboxylation of L -DOPA. OHOHOHOH H H H H H2NH2NH2NH2N HOHOHOHO Dopamine

Neurotransmitters OHOHOHOH H H H OH H2NH2NH2NH2N HOHOHOHO Norepinephrine

Neurotransmitters OHOHOHOH H H H OH CH 3 NH HOHOHOHO Epinephrine