17
incompletely separated fractions and based too much reliance on cryoscopic measurements of molecular weights, which led to many anomalous results.
From 1935 to 1950, epoch called by French (1957a) the “maturation period,” the
works of Freudenberg on the chemistry of the Schardinger dextrins were acknowledged to have made an important contribution to the cyclodextrin science
(Freudenberg and Jacobi 1935; Freudenberg and Rapp 1936; Freudenberg et al.
1936, 1938, 1939, 1947a, b; Freudenberg and Meyer-Delius 1938, 1939; Freudenberg
1939, 1943; Freudenberg and Cramer 1948, 1950). Indeed, Freudenberg is recognized as a pioneer in this domain (Thoma and Stewart 1965; Caesar 1968). As far
back as 1922, Freudenberg was the first researcher to focus on the chemical modification of dextrins, in particular of tosylated residues (Freudenberg and Ivers 1922).
Later, the Schardinger dextrins were oxidized by iodite, “probably by a glycolcleavage reaction” (Freudenberg 1934). Enzymatic hydrolysis gave no trace of a
sugar unit other than D-glucose (Freudenberg and Jacobi 1935). During the hydrolysis of dextrins, Freudenberg also observed an increase in rotation due to hydrolysis of the β-linkage. During acetolysis, the dextrins were shown to be more nearly
similar to starch than to compounds of the levoglucosan type. Using a cryoscopic
method for the determination of molecular weights, Freudenberg reported (erroneously) the number of glucose units that the Schardinger dextrins contained: five for
Α-dextrin and six for β-dextrin (Freudenberg and Jacobi 1935). In 1936, Freudenberg
confirmed that enzymatic hydrolysis gave no trace of a sugar unit other than
D-glucose. He also reported that methylation studies failed to reveal the presence of
any D-glucose units, concluding that glucose was the only product of acid hydrolysis of dextrins (Freudenberg and Rapp 1936). The following pieces of experimental
evidence were also published: (i) the rate of hydrolysis of dextrins in 51% sulfuric
acid was too low for there to be any labile β-linkages present; (ii) the Schardinger
dextrins were non-reducing, that is, they did not have a reducing chain termination;
and (iii) methylation studies on dextrins gave no products than 2,3,6-O-methyl-Dglucose (Freudenberg and Rapp 1936). The same year, Freudenberg prepared fully
methylated α- and β-dextrins and finally demonstrated that 2,3,6-tri-methylglucose
was the only product of methylation of dextrins followed by hydrolysis (Freudenberg
et al. 1936). Later, acetate derivatives of the dextrins were proposed and characterized for the first time (Freudenberg et al. 1947a, b). In 1955, Freudenberg published
a detailed description of the chemistry of the three main cyclodextrins (Freudenberg
1955), and in 1962, he summarized all his results (Freudenberg 1962).
Between 1942 and 1950, French published numerous important contributions on
the chemistry of the Schardinger dextrins (French and Rundle 1942; Rundle and
French 1943; Bates et al. 1943; French et al. 1948, 1949a, b, 1950a, b, 1954; French
and McIntire 1950; Norberg and French 1950). Very quickly, like Freudenberg,
French became a pioneer in the understanding of their chemistry (Thoma and
Stewart 1965; Caesar 1968; Szejtli 1998; Crini 2014). French showed that the
Schardinger dextrins, being cyclic, had no non-reducing end group and they were
extremely resistant to alpha-type amylases. Using data from periodate oxidation
and methylation reactions, he demonstrated that Schardinger dextrins could not be
open-chain compounds. Periodate oxidation was slow with Schardinger dextrins in
1 History of Cyclodextrins
incompletely separated fractions and based too much reliance on cryoscopic measurements of molecular weights, which led to many anomalous results.
From 1935 to 1950, epoch called by French (1957a) the “maturation period,” the
works of Freudenberg on the chemistry of the Schardinger dextrins were acknowledged to have made an important contribution to the cyclodextrin science
(Freudenberg and Jacobi 1935; Freudenberg and Rapp 1936; Freudenberg et al.
1936, 1938, 1939, 1947a, b; Freudenberg and Meyer-Delius 1938, 1939; Freudenberg
1939, 1943; Freudenberg and Cramer 1948, 1950). Indeed, Freudenberg is recognized as a pioneer in this domain (Thoma and Stewart 1965; Caesar 1968). As far
back as 1922, Freudenberg was the first researcher to focus on the chemical modification of dextrins, in particular of tosylated residues (Freudenberg and Ivers 1922).
Later, the Schardinger dextrins were oxidized by iodite, “probably by a glycolcleavage reaction” (Freudenberg 1934). Enzymatic hydrolysis gave no trace of a
sugar unit other than D-glucose (Freudenberg and Jacobi 1935). During the hydrolysis of dextrins, Freudenberg also observed an increase in rotation due to hydrolysis of the β-linkage. During acetolysis, the dextrins were shown to be more nearly
similar to starch than to compounds of the levoglucosan type. Using a cryoscopic
method for the determination of molecular weights, Freudenberg reported (erroneously) the number of glucose units that the Schardinger dextrins contained: five for
Α-dextrin and six for β-dextrin (Freudenberg and Jacobi 1935). In 1936, Freudenberg
confirmed that enzymatic hydrolysis gave no trace of a sugar unit other than
D-glucose. He also reported that methylation studies failed to reveal the presence of
any D-glucose units, concluding that glucose was the only product of acid hydrolysis of dextrins (Freudenberg and Rapp 1936). The following pieces of experimental
evidence were also published: (i) the rate of hydrolysis of dextrins in 51% sulfuric
acid was too low for there to be any labile β-linkages present; (ii) the Schardinger
dextrins were non-reducing, that is, they did not have a reducing chain termination;
and (iii) methylation studies on dextrins gave no products than 2,3,6-O-methyl-Dglucose (Freudenberg and Rapp 1936). The same year, Freudenberg prepared fully
methylated α- and β-dextrins and finally demonstrated that 2,3,6-tri-methylglucose
was the only product of methylation of dextrins followed by hydrolysis (Freudenberg
et al. 1936). Later, acetate derivatives of the dextrins were proposed and characterized for the first time (Freudenberg et al. 1947a, b). In 1955, Freudenberg published
a detailed description of the chemistry of the three main cyclodextrins (Freudenberg
1955), and in 1962, he summarized all his results (Freudenberg 1962).
Between 1942 and 1950, French published numerous important contributions on
the chemistry of the Schardinger dextrins (French and Rundle 1942; Rundle and
French 1943; Bates et al. 1943; French et al. 1948, 1949a, b, 1950a, b, 1954; French
and McIntire 1950; Norberg and French 1950). Very quickly, like Freudenberg,
French became a pioneer in the understanding of their chemistry (Thoma and
Stewart 1965; Caesar 1968; Szejtli 1998; Crini 2014). French showed that the
Schardinger dextrins, being cyclic, had no non-reducing end group and they were
extremely resistant to alpha-type amylases. Using data from periodate oxidation
and methylation reactions, he demonstrated that Schardinger dextrins could not be
open-chain compounds. Periodate oxidation was slow with Schardinger dextrins in
1 History of Cyclodextrins