54
“expected 25-30 participants outside Hungary.” The 63 submitted manuscripts filled a
544-page volume of proceedings published by Reidel Publishing (Szejtli 1982c). The
second cyclodextrin symposium was organized in 1984 in Tokyo, Japan.
Since 1984 and Szejtli’s initiative, a broad community of researchers has met
every 2 years to exchange and share their works on cyclodextrins. Each symposium
provides opportunities for scientists who work in several aspects of cyclodextrin
research to discuss their advances in all cyclodextrin fields. The 19th International
Cyclodextrin Symposium was held in 2018 in Tokyo, Japan, and the next will be
organized in Sicily, Italy, in 2020. In Asia and in Europe, the cyclodextrin scientific
community is also very active with the organization of meetings where academic
researchers and industrials come together to present the latest achievements in the
field of cyclodextrin science and technology, e.g., Asian Cyclodextrin Conferences,
European Conferences, and French Cyclodextrin Days.
1.4.9 Cyclodextrin Derivatives
The underivatized or native β-cyclodextrin’s low water solubility as showed by
French in the 1940s restricted its advantage. For this reason, a number of derivatives
such as hydrophilic methylated derivatives have been synthesized. Whereas the first
methylated derivatives of β-cyclodextrins were studied as early as 1924 by
Pringsheim and collaborators (Irvine et al. 1924), it was however not until 1969 that
the alkylated cyclodextrins were comprehensively described by Gramera (1969).
Indeed, in the older literature, particularly in the works of Pringsheim and
Freudenberg, several methods were proposed referring to the preparation of such
derivatives, but these are essentially of historic interest.
Literature on the preparation and investigation of cyclodextrin derivatives only
proliferated in the 1960s. Since, numerous cyclodextrin derivatives and polymers
were described, including alkylated and acylated derivatives, nitrogen- and sulfurcontaining derivatives, halogenated products, and 6-deoxy derivatives. The derivatives of practical importance were the methylated and hydroxypropyl cyclodextrin
derivatives in the 1980s and 10 years later the sulfobutyl ether derivatives. Casu was
the first to prepare cyclodextrin derivatives such as methylated (Casu et al. 1968a, c)
and acetylated (Casu et al. 1970) products. The experimental protocols were
repeated in the 1980s by Szejtli (Szejtli 1982a, 1983, 1984). His work, particularly
on methylated cyclodextrins, showed great promise for both human and animal use
(Szejtli 1982a). Methylation could be either partial, i.e., esterification in positions 2
and 6, giving dimethyl-cyclodextrins or complete giving trimethyl-cyclodextrins.
The randomized derivative called RAMEB was often used. These derivatives were
much more soluble than the parent cyclodextrins, but their solubility was
temperature- dependent. For this reason, hydroxypropyl cyclodextrins with high
water solubility were more advantageous. However, because hydroxypropylation
occurred randomly, the resulting products were not pure chemical entities but amorphous complex mixtures.
Croft and Bartsch (1983) were the first to publish a review on all the different
chemically modified cyclodextrins which had been synthetized up to late 1982. In
N. Morin-Crini et al.
“expected 25-30 participants outside Hungary.” The 63 submitted manuscripts filled a
544-page volume of proceedings published by Reidel Publishing (Szejtli 1982c). The
second cyclodextrin symposium was organized in 1984 in Tokyo, Japan.
Since 1984 and Szejtli’s initiative, a broad community of researchers has met
every 2 years to exchange and share their works on cyclodextrins. Each symposium
provides opportunities for scientists who work in several aspects of cyclodextrin
research to discuss their advances in all cyclodextrin fields. The 19th International
Cyclodextrin Symposium was held in 2018 in Tokyo, Japan, and the next will be
organized in Sicily, Italy, in 2020. In Asia and in Europe, the cyclodextrin scientific
community is also very active with the organization of meetings where academic
researchers and industrials come together to present the latest achievements in the
field of cyclodextrin science and technology, e.g., Asian Cyclodextrin Conferences,
European Conferences, and French Cyclodextrin Days.
1.4.9 Cyclodextrin Derivatives
The underivatized or native β-cyclodextrin’s low water solubility as showed by
French in the 1940s restricted its advantage. For this reason, a number of derivatives
such as hydrophilic methylated derivatives have been synthesized. Whereas the first
methylated derivatives of β-cyclodextrins were studied as early as 1924 by
Pringsheim and collaborators (Irvine et al. 1924), it was however not until 1969 that
the alkylated cyclodextrins were comprehensively described by Gramera (1969).
Indeed, in the older literature, particularly in the works of Pringsheim and
Freudenberg, several methods were proposed referring to the preparation of such
derivatives, but these are essentially of historic interest.
Literature on the preparation and investigation of cyclodextrin derivatives only
proliferated in the 1960s. Since, numerous cyclodextrin derivatives and polymers
were described, including alkylated and acylated derivatives, nitrogen- and sulfurcontaining derivatives, halogenated products, and 6-deoxy derivatives. The derivatives of practical importance were the methylated and hydroxypropyl cyclodextrin
derivatives in the 1980s and 10 years later the sulfobutyl ether derivatives. Casu was
the first to prepare cyclodextrin derivatives such as methylated (Casu et al. 1968a, c)
and acetylated (Casu et al. 1970) products. The experimental protocols were
repeated in the 1980s by Szejtli (Szejtli 1982a, 1983, 1984). His work, particularly
on methylated cyclodextrins, showed great promise for both human and animal use
(Szejtli 1982a). Methylation could be either partial, i.e., esterification in positions 2
and 6, giving dimethyl-cyclodextrins or complete giving trimethyl-cyclodextrins.
The randomized derivative called RAMEB was often used. These derivatives were
much more soluble than the parent cyclodextrins, but their solubility was
temperature- dependent. For this reason, hydroxypropyl cyclodextrins with high
water solubility were more advantageous. However, because hydroxypropylation
occurred randomly, the resulting products were not pure chemical entities but amorphous complex mixtures.
Croft and Bartsch (1983) were the first to publish a review on all the different
chemically modified cyclodextrins which had been synthetized up to late 1982. In
N. Morin-Crini et al.