Intro to Amino acids and Carbohydrates

Amino acid FG characteristics

An alpha carbon has an amino group, carboxylic acid, Hydrogen and an R group or side chain

Exists as a zwitterion, a molecule that has sperate positive key and negative le charged groups

How does Fischer’s diagram draw an L-AA

L-amino acid has the amino group on the left, (most oxidided C) carboxylic acid at the top, R group on the bottom and H on the right

R-AA is the mirror reflection of this

Isoelectronic point equation

$$IEP=\frac{pka_1+pka_2}{2}$$

3 synthesis methods for AA (Name, reaction type, state SM and reagents)

Streckers AA Synthesis: carbonyl undergoes nucleophillic addition and then acidic nitrile hydrolysis

Ammounium salt and cyanide is added to carbonyl, and then an acid (and water) is used to oxidise cyanide

SN2 of alpha-halocarboxylic acid: SN2 with excess ammonia

Reductive amination: alpha-keto acid undergoes nucleophillic substitution followed by reduction of alpha carbon

alpha-keto acid has ammonium salt added and then NaBH_4 to reduce

Characteristics of peptide structure

Peptide bond has the carboxylic acid and amine group, excluding the OH and one of the H

General pattern for L AA: alternating R groups (Up and down)

Stoichemetric properties for peptide bonds

Peptide bonds are planar

Most peptides exist in the trans form → avoids steric clash (except proline and glycine; can exist in both)

Purpose for protecting groups (PGs)

Essential for reaction with AA and helps control peptide synthesis, to determine which side reacts and doesn’t

When do we use amino PG

For when we want the CA group to be free to react, but not the amine group

Cbz (carbobenzyloxy) trigger and installation

Nucleophillic addition

Reagent: Cbz-Cl (benzoyl chloroformate) (PG, E+)

Base: mild such as NaOH

Solvent: aqueous or organic such as THF/H2O

Trigger is chloroformate and mild base

Cbz (carbobenzyloxy) removal

Hydrogenolysis (involving carboxylation) OR nucleophilic attack

Reagents: H_2 OR HBr

Solvent: MeOH / EtOH OR AcOH

(Neutral conditions)

Fmoc ( Fluoronylmethyloxycarbonyl) Installation and trigger

Nucleophillic addition

Reagent: Fmoc (PG, E+)

Base: mild such as Na_2CO_3

Solvent: aqueous or organic such as THF/H2O

Trigger is Fmoc and mild base

Fmoc ( Fluoronylmethyloxycarbonyl) removal

PT and decarboxylation

Reagents: Excess piperidine (base

Solvent: DMF

(Basic conditions)

Boc ( tert-Butyloxycarbonyl)Installation and trigger

Nucleophillic addition

Reagent: Boc anhydride (E+)

Base: mild such as NaOH

Solvent: aqueous or organic such as THF/H2O

Trigger is anhydride and mild base

Boc ( tert-Butyloxycarbonyl) removal

PT (acidic)

Reagents: Excess Trifluoroacetate, TFA (acid)

Solvent: CH_2Cl_2

(Acidic conditions)

When do we use carboxylic PG

For when we want the amino group to be free to react, but not the Carboxyl group

Benzyl esters Installation and trigger

Esterification

Reagent: Benzyl alcohol

Conditions: Acid catalyst such as PTSA or TsOH, Toulene, reflux,

Solvent: DCM

Benzyl esters removal

Electrophilic addition / Hydrogenolysis (involving carboxylation) OR nucleophilic attack

Reagents: H_2 OR HBr

Solvent: MeOH / EtOH OR AcOH

(Neutral conditions)

Methyl or Ethel esters Installation and trigger

Fischer Esterification

Reagent: MeOH or EtOG

Conditions

Strong acid such as HCl

Solvent: AcCl

Methyl or Ethel esters removal

Hydrolysis

Reagent and conditions

HCl and H_2O

Acidic conditions as basic hydrolysis may cause problems

Tert-Butyl esters Installation and trigger

Reagent: Isobutene

Conditions

Acid catalyst: N_2SO_4

Solvent: CH_2Cl_2

Tert-Butyl esters removal

Reagent: TFA in excess

Solvent: CH_2Cl_2

Patterns in removal

Benzyl groups - H_2/Pd

Tert-Butyl and simple esters - acid conditions

Fmoc - basic conditions

What is the purpose of peptide coupling

Reagents and conditions for peptide coupling using DCC as a base

Reagents and conditions for peptide coupling using Et_3N as a base

Consequences of peptide coupling