Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
2 Enantiomer Separation by HPLC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
3 Molecular-Type CSPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
4 Polymer-Type CSPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
5 Polymethacrylates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
6 Polyacrylamides and Polymethacrylamides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
7 Polyacetylenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
8 Poly(α-amino acids) and Polyamides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
9 Other Synthetic Polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
10 Natural Polymers and Their Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
10.1 Cellulose Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
10.2 Amylose Phenylcarbamates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
10.3 Other Carbamate Derivatives of Cellulose and Amylose . . . . . . . . . . . . . . . . . . . . . . . . 405
10.4 Chiral Recognition Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
10.5 Other Polysaccharide Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
11 Recent Situation Regarding Chromatographic Chiral Separations . . . . . . . . . . . . . . . . . . . . . . 408
12 Preparative Separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
13 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
1 Introduction
In 1848, Louis Pasteur succeeded in the first separation (resolution) of enantiomers
by the direct crystallization of racemic sodium tartrate. He and coworkers also
established other separation methods, including the crystallization of diastereomeric salts and the kinetic resolution of racemic hydrolyzable substrates using
enantioselective biocatalysts such as enzymes. However, during his studies, it
was impossible to perform the resolution of enantiomers by column chromatography because the chromatographic separation method had not yet been developed.
The first baseline separation of enantiomers by liquid chromatography was attained
for racemic amino acids using the ligand exchange method by Davankov in 1971
[1], and thereafter, many chiral stationary phases (CSP) for high-performance
liquid chromatography (HPLC) have been developed [2, 3]. Today, this method
of enantiomer separation has become very practical not only for analyzing chiral
compounds, but also for obtaining pure enantiomers. The CSPs are classified into
two categories. The first is molecular-type CSPs based on small molecules capable
of chiral recognition and the second is polymer-type CSPs based on optically active
polymers. Among more than one hundred commercially available CSPs, the
polymer-type CSPs with a helical conformation are most frequently used
[4–6]. This chapter mainly describes the polymer-type CSPs with helical structures
developed in my group [7].
392
Y. Okamoto
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
2 Enantiomer Separation by HPLC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
3 Molecular-Type CSPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
4 Polymer-Type CSPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
5 Polymethacrylates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
6 Polyacrylamides and Polymethacrylamides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
7 Polyacetylenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
8 Poly(α-amino acids) and Polyamides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
9 Other Synthetic Polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
10 Natural Polymers and Their Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
10.1 Cellulose Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
10.2 Amylose Phenylcarbamates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
10.3 Other Carbamate Derivatives of Cellulose and Amylose . . . . . . . . . . . . . . . . . . . . . . . . 405
10.4 Chiral Recognition Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
10.5 Other Polysaccharide Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
11 Recent Situation Regarding Chromatographic Chiral Separations . . . . . . . . . . . . . . . . . . . . . . 408
12 Preparative Separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
13 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
1 Introduction
In 1848, Louis Pasteur succeeded in the first separation (resolution) of enantiomers
by the direct crystallization of racemic sodium tartrate. He and coworkers also
established other separation methods, including the crystallization of diastereomeric salts and the kinetic resolution of racemic hydrolyzable substrates using
enantioselective biocatalysts such as enzymes. However, during his studies, it
was impossible to perform the resolution of enantiomers by column chromatography because the chromatographic separation method had not yet been developed.
The first baseline separation of enantiomers by liquid chromatography was attained
for racemic amino acids using the ligand exchange method by Davankov in 1971
[1], and thereafter, many chiral stationary phases (CSP) for high-performance
liquid chromatography (HPLC) have been developed [2, 3]. Today, this method
of enantiomer separation has become very practical not only for analyzing chiral
compounds, but also for obtaining pure enantiomers. The CSPs are classified into
two categories. The first is molecular-type CSPs based on small molecules capable
of chiral recognition and the second is polymer-type CSPs based on optically active
polymers. Among more than one hundred commercially available CSPs, the
polymer-type CSPs with a helical conformation are most frequently used
[4–6]. This chapter mainly describes the polymer-type CSPs with helical structures
developed in my group [7].
392
Y. Okamoto