Enantiomers resolution

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BY ...Javed khan Beijing
university of chemica technology

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Table of contents

• Chromatography
• Various types of chromatography
• Classification on the basis of mechanism
• Enantiomers
• Enantiomers Resolution
• Enantiomers Resolution Using HPLc
• Enantiomers resolution using Polymeric type of
  chiral stationary phase in HPLC
• Enantiomers resolution using Molecular type of
  chiral stationary phase in HPLC
• Enantiomers resolution By PTrMa
• Enantiomers resolution By Polysaccharide
• Enantiomers resolution By Cellulose derivatives
• Enantiomers resolution By Crown Ether
• Enantiomers resolution By Amylose

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Chromatography
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Types of chromatography
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Classification on the basis of mechanism
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Enantiomers

• Enantiomers are chiral molecules that are mirror
  images of one another. Furthermore, the molecules
  are non-superimposable on one another. This means
  that the molecules cannot be placed on top of one
  another and give the same molecule. Chiral
  molecules with one or more stereocenters can be
  enantiomers.

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Enantiomers resolution

• Method Development and Optimization of
  Enantioseparations Using Macrocyclic Glycopeptide
  Chiral Stationary Phases.
• Role of Polysaccharides in Chiral Separations by
  Liquid Chromatography and Capillary
  Electrophoresis
• Chiral Separation by Ligand Exchange
• Countercurrent Chromatography in the Separation
  of Enantiomers
• Separation of Enantiomers Using Molecularly
  Imprinted Polymers
• Advances in Simulated Moving Bed Chromatographic
  Separations.
• Less Common Applications of Enantioselective HPLC
  Using the SMB Technology in the Pharmaceutical
  Industry.

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Enantiomers resolution using HPLC

• High-performance liquid chromatography (HPLC
  formerly referred to as high-pressure liquid
  chromatography), is a technique in analytical
  chemistry used to separate, identify, and
  quantify each component in a mixture. It relies
  on pumps to pass a pressurized liquid solvent cont
  aining the sample mixture through a column filled
  with a solid adsorbent material. Each component
  in the sample interacts slightly differently with
  the adsorbent material, causing different flow
  rates for the different components and leading to
  the separation of the components as they flow out
  the column.

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Enantiomers resolution using Polymeric type of
chiral stationary phase in HPLC

• Well know polymers used in literature as
  stationary phase
• Poly (meth)acrylamide
• Poly (meth) acrylate
• Polyesterene
• Polymaleimide
• Poly (acetylene)
• Cellulose
• Amylose
• Polyisocyanide

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Resolution of Racemates using Molecular type
Chiral type CSPs in HPLC
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Enantiomer resolution by chromatography Using CSP

• 
  DOI 10.1021/acs.chemrev.5b00317
• 
  Chem. Rev. 2016, 116, 1094-1138

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Enantiomer resolution through PTrMA

• Polymethacrylate is one of the most efficient CSP
  used as stationary phase in HPLC and in other
  chromatographic techniques, thousands of
  racemates have been resolved by using PTrMA, The
  first successful preparation of one-handed
  helical polymethacrylate, PTrMA, with a nearly
  100 isotacticity was achieved by the
  helix-senseselective polymerization of an achiral
  bulky monomer, TrMA using the complex of
  n-butyllithium (n-BuLi) with a chiral ligand,
  (-)-sparteine ((-)-Sp), in 1979,
• DOI
  10.1021/acs.chemrev.5b00317
• Chem. Rev.
  2016, 116, 1094-1138

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PTrMA Analogous
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Racemates seperated by PTrMA.
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Polysaccharides as CSP in HPLC

• Polysaccharide derivatives have been extensively
  used as chromatographic chiral selectors in
  chiral stationary phases
• (CSPs) for the separation of enantiomers by HPLC.
  When coated onto a silica matrix, they represent
  nowadays one of the
• most popular type of CSPs.

P. Franco et al. / J. Chromatogr. A 906 (2001)
155 170
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Preparation

• Polysaccharide-derived CSPs supported on silica
  Okamoto et al. described in 1987 the first
  preparation gel are classically prepared by
  reaction of the of CSPs in which the
  polysaccharide was bonded to polysaccharide with
  a benzoyl chloride or a phenyl a
  g-aminopropylsilica gelmatrix. The resulting CSPs
  are commercially available and can be mainly used
  with hydrocarbon/ ability of polysaccharides, in
  particular cellulose, alcohol or hydrocarbon/
  ether mixtures.

P. Franco et al. / J. Chromatogr. A 906 (2001)
155 170
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Fixation of cellulose on silica gels of different
pore size
Fig. 7. Fixation of 10-undecenoate/
3,5-dimethylphenylcarbamates of cellulose onto
allylsilica gels of different pore size.
Relationship between silica gel pore size (log
scale) and (I) the carbon content on intermediate
allylsilica gels and (II) the amount of cellulose
derivative fixed on the CSP 29
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Racemates resolved by polysacharride
Chemical structures of some of the racemic
compounds used to test the CSPs.
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Chiral recognition of carboxylic acid
functionalized cellulose tris(3,5-dimethylphenylca
rbamate).

• Cellulose is one of the most abundant natural
  materials and attracts wide interest due to its
  unique physical and chemical properties. Chemical
  modification of the hydroxyl groups of the
  anhydroglucose unit (AGU) in cellulose leads to
  the produc-tion of high value-added advanced
  materials, such as membranes, biomimetic
  actuators and chiral stationary phases (CSPs) for
  HPLC

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Immobilization of cellulose derivatives onto
silica gel.
Fig. 1. Synthesis (a) and1H NMR spectra (b) of
CDMPC and carboxylic acid functionalized CDMPC
(CC-1.8).
Fig. 2. Scheme of immobilization of CC-Xs onto
mesoporous amine-modified silica gel.
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Structure of Racemates resolved.
Figure 3 Structure of Racemates
Figure 4 SEM pictures of immobilized CC-1.8-18
CSP (left) and coated-type CDMPC CSP (right). The
scale bar represents 10 .
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Racemates resolution with different mobile phases
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Important Racemates Resolved
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Enantiomers resolution Using Crown ether
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Crown ether as stationary phase on Silica.
Structure of a crown ether CSP covalently bonded
to silica gel
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Amylose and its derivatives as CSP

• Amylose is a polysaccharide made of
  a-D-glucose units, bonded to each other through
  a(1?4) glycosidic bonds It is one of the two
  components of starch making up approximately
  20-30. The other component is amAmylose is made
  up of a(1?4) bound glucose molecules. The carbon
  atoms on glucose are numbered, starting at the
  aldehyde (CO) carbon, so, in amylose, the
  1-carbon on one glucose molecule is linked to the
  4-carbon on the next glucose molecule (a(1?4)
  bonds). The structural formula of amylose is
  pictured at right. The number of repeated glucose
  subunits (n) is usually in the range of 300 to
  3000, but can be many thousands.

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Immobilization process of amylose derivative onto
silica gel only at the reducing terminal residue.
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Racemates resolved on Amylose and its Derivatives
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Important Racemates resolved
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Finished