Asymmetric Synthesis 2

Question 1

What are the different methods of resolution of enantiomers?

Answer 1

physical methods

• conglomerate
• racemic compound
• pseudoracemate

chemical

• conversion to a mixture of diastereoisomers
• kinetic resolution
• biochemical methods
• form diastereomeric salts
• chiral chromatography

Question 2

What are the physical methods of resolution?

Answer 2

conglomerate = only one that can be physically separated

• enantiomers when they crystallise tend to stick together in a conglomerate
• large crystals will look slightly different and can be separated by hand

racemic compounds
- when molecules have a higher affinity for the opposite enantiomer

pseudoracemate
- no affinity for one or the other so a disordered lattice forms

Question 3

How does conversion to a mixture of diastereoisomers work?

Answer 3

1 - derivatization with chiral reagents
= reacts with acetic anhydride and adds acetate at the amino group
= Ac protects the amino group from the reaction

2 - conversion to a mixture of diastereoisomeric esters using a chiral pool compound

3 - separation of the diastereoisomers by recrystallisation

4 - removal of the extra groups
= removal of the ester by hydrolysis in potassium hydroxide

5 - deprotect the amino group
= removal of the acetate by amide hydrolysis in sodium hydroxide

Question 4

What are the ideal properties of diastereoisomers for resolution via conversion to a mixture of diastereoisomers work?

Answer 4

must be

• easily and quickly formed
• be easily purified
• easily and quickly disjoined

Question 5

How does conversion to diastereoisomeric salts work?

Answer 5

1 - reaction with a base (must be chiral)
= reacts with chiral amine to form a diastereoisomeric mixture

2 - physical method of separation

3 - acidify
= generates the free acid (carboxylic acid)

separate the enantiomers formed

Question 6

How does chiral chromatography work?

Answer 6

a chiral stationary phase is used which retains one enantiomer more than the other
- due to their different interactions with the chiral phase

can be used in GC, HPLC and TLC

Question 7

How does kinetic resolution work?

Answer 7

enantiomers will react with other chiral compounds at different rates

• if these rates are different enough, one can be converted while the other is not
• they then can be separated

maximum yield is only 50%

Question 8

How does biochemical methods of resolution work?

Answer 8

is a special case of kinetic resolution

a stereoselective enzymatic conversion of one enantiomer takes place
- enzymes convert only one enantiomer leaving the other to be separated

Question 9

How can diastereoisomers be separated when being resolved via conversion to a mixture of diastereoisomers?

Answer 9

chromatography
selective recrystallisation
distillation

Question 10

Which method is most suitable for the resolution of a racemic mixture of amino acids?

Answer 10

conversion to diastereomeric salts.