12 Preparative Separation
Concerning the large-scale preparative separation of enantiomers, we can use the
simulated-moving bed (SMB) system. This chromatographic system is useful for
the separation of two components and has been used in industry to purify sugars
using ion-change resins as stationary phases. Fortunately, enantiomers are two
components and, therefore, we can readily use this industrial system for the
separation of chiral compounds using the polysaccharide-based CPMs. Several
chiral drugs or intermediates have been industrially resolved by SMB using the
polysaccharide-based CPMs [66]. A CPM suitable for preparative resolution has
also been developed as an organic–inorganic hybrid material [67]
13 Concluding Remarks
In 1979, we found that a vinyl polymer, PTrMA, with a stable one-handed helical
structure can be directly synthesized through the asymmetric anionic polymerization of TrMA by the (À)-sparteine-BuLi complex in toluene. This is the first
example of the asymmetric synthesis of a helical polymer and proved that such a
helical polymer can stably exist without optically active side groups. The helical
PTrMA exhibited an unexpected high chiral recognition of many racemates, particularly stereochemically interesting compounds. In 1982, the chiral column was
commercialized as the first chiral column based on an optically active polymer. As
described in this chapter, following this study, many helical polymers were
synthesized for evaluation as CSPs for HPLC, and it became clear that to attain
high chiral recognitions, regular helical structures of the polymer chains is very
important. Besides the synthetic polymers, we also extended our studies to polysaccharide derivatives. In 1984, we found that cellulose trisphenylcarbamate with a
helical conformation functions as an excellent CSP when coated on silica gel. This
finding had been extended to many other carbamate derivatives and other
polysaccharides, including amylose. Among the many polysaccharide derivatives
we synthesized, the 3,5-dimethylphenylcarbamates of cellulose and amylose are
currently the most popular CSPs; with these four or five polysaccharide-based
CSPs, nearly 90% of the chiral compounds can be resolved. The contribution of
these CSPs to the research and development of chiral compounds, including many
drugs, has been remarkable. The high abilities of these CSPs are closely related to
their rather rigid helical structures.
Acknowledgment The author gratefully thanks many teachers, coworkers, and students for their
advice, suggestions, discussion, and experimental work. The author gratefully acknowledges
financial supports by the Grant-in-Aids of the Ministry of Education, Culture, Sports, Science
and Technology of Japan and by Daicel Corporation.
410
Y. Okamoto
Concerning the large-scale preparative separation of enantiomers, we can use the
simulated-moving bed (SMB) system. This chromatographic system is useful for
the separation of two components and has been used in industry to purify sugars
using ion-change resins as stationary phases. Fortunately, enantiomers are two
components and, therefore, we can readily use this industrial system for the
separation of chiral compounds using the polysaccharide-based CPMs. Several
chiral drugs or intermediates have been industrially resolved by SMB using the
polysaccharide-based CPMs [66]. A CPM suitable for preparative resolution has
also been developed as an organic–inorganic hybrid material [67]
13 Concluding Remarks
In 1979, we found that a vinyl polymer, PTrMA, with a stable one-handed helical
structure can be directly synthesized through the asymmetric anionic polymerization of TrMA by the (À)-sparteine-BuLi complex in toluene. This is the first
example of the asymmetric synthesis of a helical polymer and proved that such a
helical polymer can stably exist without optically active side groups. The helical
PTrMA exhibited an unexpected high chiral recognition of many racemates, particularly stereochemically interesting compounds. In 1982, the chiral column was
commercialized as the first chiral column based on an optically active polymer. As
described in this chapter, following this study, many helical polymers were
synthesized for evaluation as CSPs for HPLC, and it became clear that to attain
high chiral recognitions, regular helical structures of the polymer chains is very
important. Besides the synthetic polymers, we also extended our studies to polysaccharide derivatives. In 1984, we found that cellulose trisphenylcarbamate with a
helical conformation functions as an excellent CSP when coated on silica gel. This
finding had been extended to many other carbamate derivatives and other
polysaccharides, including amylose. Among the many polysaccharide derivatives
we synthesized, the 3,5-dimethylphenylcarbamates of cellulose and amylose are
currently the most popular CSPs; with these four or five polysaccharide-based
CSPs, nearly 90% of the chiral compounds can be resolved. The contribution of
these CSPs to the research and development of chiral compounds, including many
drugs, has been remarkable. The high abilities of these CSPs are closely related to
their rather rigid helical structures.
Acknowledgment The author gratefully thanks many teachers, coworkers, and students for their
advice, suggestions, discussion, and experimental work. The author gratefully acknowledges
financial supports by the Grant-in-Aids of the Ministry of Education, Culture, Sports, Science
and Technology of Japan and by Daicel Corporation.
410
Y. Okamoto