WK1- Chiral Method - resolution and enzyme

What is an enantiomer?

Non-superimposable mirror images. Same physical properties except optical rotation and interaction with chiral molecules.

What is a diastereomer?

Stereoisomers that are NOT mirror images. Different physical properties (m.p., solubility, Rf on TLC).

What makes a carbon atom a chiral centre?

It is bonded to 4 different groups (sp³ hybridised).

What is the maximum yield of a desired enantiomer in standard kinetic resolution?

50% (the other enantiomer remains unreacted).

What are the three steps to assign R/S configuration?

1. Priority by atomic number. 2. Put lowest priority (H) at the back. 3. Trace 1→2→3: clockwise = R, anticlockwise = S.

What is the formula for enantiomeric excess (ee) from optical rotation?

% ee = (observed specific rotation / pure enantiomer rotation) × 100

If enantiomeric excess is 20%, what is the mixture composition?

60% : 40% (because 60 − 40 = 20% excess).

Name three methods to separate enantiomers.

1. Diastereomeric salts. 2. Chiral HPLC. 3. Kinetic resolution.

How does diastereomeric salt resolution work?

Add a chiral resolving agent (e.g., chiral base to racemic acid) → forms two diastereomeric salts with different solubility → crystallize one out.

Why can diastereomers be separated by crystallization but not enantiomers?

Diastereomers have different physical properties (solubility, melting point). Enantiomers have identical solubility in an achiral environment.

How does chiral HPLC with a cyclodextrin column work?

Inclusion complex: molecule fits inside cyclodextrin cavity. Para isomer fits best → elutes last. Ortho and meta elute first.

What is spontaneous resolution (Pasteur)?

Manual separation of mirror-image crystals under a microscope. Not practical for large scale.

What is kinetic resolution?

A chiral catalyst or enzyme reacts with one enantiomer faster than the other. The other enantiomer remains unreacted.

What does Baker's yeast do in chiral synthesis?

It reduces ethyl acetoacetate to a chiral alcohol (enantioselective reduction).

What does lipase do in chiral synthesis?

It hydrolyses the ester of the R-enantiomer faster, leaving the S-enantiomer untouched.

Do enzymes have broad or limited substrate scope?

Limited substrate scope. They are highly selective but work on few substrates.

What is an industrial example of enzymatic resolution?

Bayer (EP 0812363 B1) using an enzyme to make one enantiomer of a drug intermediate.

What is the advantage of a chiral auxiliary?

Excellent enantiomeric ratio (er).

What is the disadvantage of a chiral auxiliary?

Extra steps to add and remove the auxiliary.

What is the advantage of a chiral reagent?

Excellent enantiomeric ratio (er).

What is the disadvantage of a chiral reagent?

Few examples, limited substrate scope.

What is the advantage of a chiral catalyst?

Economical (catalytic amount).

What is the disadvantage of a chiral catalyst?

Few examples.

What is the advantage of resolution (classical / kinetic)?

Both enantiomers are available.

What is the disadvantage of resolution?

Maximum 50% yield.

What is the advantage of the chiral pool method?

99:1 enantiomeric ratio.

What is the disadvantage of the chiral pool method?

Limited substrates and stereochemistry (e.g., amino acids, sugars).

What does [α]D^25 mean in polarimetry?

D-line of sodium lamp (589.6 nm) at 25°C temperature.

In cyclodextrin chiral HPLC, which isomer fits best into the cavity and elutes last?

Para isomer fits best and elutes last.

What is the maximum yield from diastereomeric salt formation?

50% (only one enantiomer crystallizes first).

What is the difference between enantiomers and diastereomers in terms of physical properties?

Enantiomers have identical physical properties except optical rotation. Diastereomers have different physical properties (m.p., solubility, Rf).

What is the difference between clockwise and anticlockwise in R/S naming?

Clockwise from 1→2→3 = R. Anticlockwise = S.