METHODS OF ASYMMETRIC SYNTHESIS USING

CHIRAL POOL

Guided by
Dr. Shailaja B. Jadhav
Submitted By Master of Pharmacy Department of Pharmaceutical
Mr. Vaibhav Shivaji Mali (Pharmaceutical chemistry) chemistry

Progressive Education Societys

Modern College Of Pharmacy,
Yamunanagar, Nigdi, Pune 2022-2023 1
 Content

• Introduction
• Importance of asymmetric synthesis
• Chiral pool synthesis
• Types of asymmetric synthesis.
• Methods of partial asymmetric synthesis.
• Bibliography
 Introduction
Asymmetric synthesis :

 The process of conversion of an achiral compound into

chiral compound in such a way that both enantiomers
termed in unequal amount.

 These reactions forms stereoisomeric products in un

equal amount.

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Importance of asymmetric synthesis:

 To access enantiomerically pure molecules for biological

applications as a drugs. hence there is need for adoption of
efficient strategies for asymmetric synthesis.

 This type of reactions done under the influence of some

chiral reagent, chiral solvent, chiral catalyst, presence of
circular polarised light.

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Chiral pool synthesis:
Chiral pool refers to a collection of enantiomerically
molecules available frompure
nature.
Common chiral starting materials derived from nature include
amino acids, chiral carboxylic acids and monosaccharides.
Examples:

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 Types of asymmetric synthesis:
1. Partial asymmetric synthesis

2. Absolute asymmetric synthesis

1. Partial asymmetric synthesis: It can be defined as synthesis

of new chiral center from achiral center by using optically
active reagents
• Methods of partial asymmetric synthesis:

1. First generation or substrate controlled asymmetric

synthesis:
The reaction where the formation of a chiral center is controlled
by another chiral center already present in the substrate is
called as 1st generation asymmetric synthesis.
Example: Hydroboration of (-)isopulegol
• Second generation method (Use of auxiliaries):
 These reactions are controlled by auxiliaries which are
chiral molecules.
 In this synthesis chirality is introduced by the attachment
of a chiral auxiliary which direct the subsequent reaction
for the formation of one enantiomer in more amount.
 After completing reaction auxiliary is get removed.
• Example- Formstion of (-)lactic acid from pyruvic acid with
the help of (-)menthol [ Chiral auxiliary]
3rd generation method [Use of chiral reagent] :
 In this reaction chiral product is formed directly by
treating an achiral starting compound with chiral reagent
.
Example : Reduction of propiophenone with LiAlH4 in
presence of proline-derived diamine gives S-1 phenyl
propanol
Reaction
4th Generation method [ Use of chiral catalyst]:
 In this reaction where reaction is influenced in the presence
of chiral catalyst.
 Enzyme catalysed reaction belongs to this class.

Example: Conversion of (-)lactic acid from pyruvic acid by yeast

or Lactic acid dehydrogenase enzyme.
Absolute asymmetric synthesis:
 It is the synthesis of optically active product from achiral
substrate without use of any optically active chemicals [ No
reagent, catalyst, solvent]
 in this type of synthesis a physical presence of chirality like
circulatory polarized light is necessary.

Example: Addition of bromine to 2,4,6 trinitrostilbene give a

dextrorotatory product by the use of circulatory polarized light
for the induction of chirality.
 Bibliography

• https://www.youtube.com/watch?v=GpGi449nKss&t=700s

• https://pubchem.ncbi.nlm.nih.gov/compound/2_4_6-Trinitrostilbene

• https://ar.iiarjournals.org/content/37/3/1205/tab-figures-data