Fundamentals of Medicinal Chemistry

Pure enantiomer

e.g. (+)B isomer Two Isomers: [(+)A−(+)B] and [(−)A−(+)B]

Diastereoisomers

Pure (+)A−(+)B

Pure (−)A−(+)B

Pure (+)A

Pure (−)A

(+)B

(+)B

Racemic modification

consisting of

Enantiomers (+)A and (−)A

Regeneration of the

enantiomer of A

Separation by the

use of physical

methods

Figure 10.4 A Schematic representation of the use of diastereoisomers in the resolution of

racemic modifications

Table 10.1 Examples of the pure enantiomers used to resolve racemic modifications by forming

diastereoisomers. In all regeneration processes there is a danger of the racemic modification being

reformed by racemization

Functional group

Enantiomers used

(resolving agents) Diastereoisomers Regeneration

Carboxylic and

other acids

A suitable base, e.g. Salts Treatment with a

suitable acid, e.g. HCl

() Brucine

() Strychnine

() Morphine

Amines and

other bases

A suitable acid, e.g. Salts Treatment with a

suitable base, e.g. NaOH

(þ) Tartaric acid

() Malic acid

(þ) Camphorsulphonic acid

Alcohols A suitable acid (see above) Esters Acid or base hydrolysis

The incorporation of the resolution of a racemic modification into a synthetic

pathway considerably reduces the overall yield of the synthesis because the

maximum theoretical yield of an enantiomer is 50 per cent unless the unwanted

enantiomer is racemized and the racemate recycled.

10. 2. 2 The use of stereoselective reactions to produce stereospecific centres

Stereoselective reactions are those that result in the selective production of one

of the stereoisomers of the product. The extent of the selectivity may be

recorded as theenantiomeric excess(e.e.) when the reaction produces a mixture

of enantiomers and thediastereoisomeric excess(d.e.) when it produces a mix-

ture of diastereoisomers. These quantities are defined by the expression:

ASYMMETRY IN SYNTHESES 207