24
I. Isoprenoids
in aquaria. In a subsequent paper,* Yamanouchi (1942) surveyed eight
species of sea cucumber and noted that all eight, including the one that is
traditionally eaten, contain in their body walls a toxic principle in varying
amount. From the most toxic species, Holothuria vagabunda, he isolated a
crystalline toxin which he named holothurin la. Yamanouchi (1942) further
noted its water solubility, its hemolytic property, and its similarity to vegetable
saponins.
Nigrelli (1952), undoubtedly unaware of Yamanouchi's prior publications,
also proposed the name holothurin for the active principle in the Cuvierian
tubules of Actinopyga agassizi. Nigrelli and Zahl (1952) noted the antitumor
activity of holothurin and its ability to kill fish, even members of the hardy
genus Carapus, the sea cucumber's frequent parasitic lodger.
Pioneer work in further definition of holothurin and in structural elucidation of the individual constituents was carried on by Nigrelli's group at the
New York Aquarium in conjunction with a molecular structure group at
Mount Sinai Hospital, New York, notably Chanley and Sobotka. By 1955
(Nigrelli et al, 1955; Chanley et al, 1955) it had become apparent that
holothurin was a steroidal (more accurately, triterpenoid) glycoside which
was hydrolyzable into closely related aglycones, several monosaccharides,
and sulfuric acid. While holothurin was transparent in the ultraviolet, acid
hydrolysis generated in the aglycone a chromophore with A m a x 244 nm, suggestive of a heteroannular diene. Nigrelli and Jakowska (1960) have concisely
summarized much of the early work. Matsuno and Yamanouchi (1961) in a
follow-up of Yamanouchi's earlier observations (1942, 1955) described the
hydrolysis of the holothurin from Holothuria vagabunda. It led to the isolation
of a genin called holothurigenin, mp 301°, [a] D +14.9°, and composition
C30H44O5. Matsuno and Yamanouchi (1961) recognized the genin as a
triterpenoid possessing three hydroxyl, a lactone, and a heteroannular diene
function.
Chanley and co-workers (1959) took advantage of the property of holothurin—which it shares with digitonin and other vegetable saponins—to
form a complex with cholesterol and precipitated about 40% of the original
glycosidic mixture as a cholesterol complex. Treatment with pyridine recovered the glycosides, which were termed holothurin A. Upon acid hydrolysis this neutral, water-soluble, nonreducing mixture was transformed into a
mixture of at least four water-insoluble aglycones, sulfuric acid, and watersoluble reducing sugars. The sugars were identified as D-xylose (60), Dglucose (61a), 3-methoxy-D-glucose (61b), and D-quinovose (6-deoxyD-glucose) (62). Enzymatic hydrolysis at pH 5.2 with an extract of Helix
pomatia (a mollusk) over 189 hours established the molecular sequence as
* I am grateful to Mr. Y. Kato for securing and translating this paper.
I. Isoprenoids
in aquaria. In a subsequent paper,* Yamanouchi (1942) surveyed eight
species of sea cucumber and noted that all eight, including the one that is
traditionally eaten, contain in their body walls a toxic principle in varying
amount. From the most toxic species, Holothuria vagabunda, he isolated a
crystalline toxin which he named holothurin la. Yamanouchi (1942) further
noted its water solubility, its hemolytic property, and its similarity to vegetable
saponins.
Nigrelli (1952), undoubtedly unaware of Yamanouchi's prior publications,
also proposed the name holothurin for the active principle in the Cuvierian
tubules of Actinopyga agassizi. Nigrelli and Zahl (1952) noted the antitumor
activity of holothurin and its ability to kill fish, even members of the hardy
genus Carapus, the sea cucumber's frequent parasitic lodger.
Pioneer work in further definition of holothurin and in structural elucidation of the individual constituents was carried on by Nigrelli's group at the
New York Aquarium in conjunction with a molecular structure group at
Mount Sinai Hospital, New York, notably Chanley and Sobotka. By 1955
(Nigrelli et al, 1955; Chanley et al, 1955) it had become apparent that
holothurin was a steroidal (more accurately, triterpenoid) glycoside which
was hydrolyzable into closely related aglycones, several monosaccharides,
and sulfuric acid. While holothurin was transparent in the ultraviolet, acid
hydrolysis generated in the aglycone a chromophore with A m a x 244 nm, suggestive of a heteroannular diene. Nigrelli and Jakowska (1960) have concisely
summarized much of the early work. Matsuno and Yamanouchi (1961) in a
follow-up of Yamanouchi's earlier observations (1942, 1955) described the
hydrolysis of the holothurin from Holothuria vagabunda. It led to the isolation
of a genin called holothurigenin, mp 301°, [a] D +14.9°, and composition
C30H44O5. Matsuno and Yamanouchi (1961) recognized the genin as a
triterpenoid possessing three hydroxyl, a lactone, and a heteroannular diene
function.
Chanley and co-workers (1959) took advantage of the property of holothurin—which it shares with digitonin and other vegetable saponins—to
form a complex with cholesterol and precipitated about 40% of the original
glycosidic mixture as a cholesterol complex. Treatment with pyridine recovered the glycosides, which were termed holothurin A. Upon acid hydrolysis this neutral, water-soluble, nonreducing mixture was transformed into a
mixture of at least four water-insoluble aglycones, sulfuric acid, and watersoluble reducing sugars. The sugars were identified as D-xylose (60), Dglucose (61a), 3-methoxy-D-glucose (61b), and D-quinovose (6-deoxyD-glucose) (62). Enzymatic hydrolysis at pH 5.2 with an extract of Helix
pomatia (a mollusk) over 189 hours established the molecular sequence as
* I am grateful to Mr. Y. Kato for securing and translating this paper.