32
/. Isoprenoids
holothurinogenin was seychellogenin (73a). It was chosen for degradation to
an intermediate 77 that was also prepared from lansterol (78). The functionalization of C-18 of lansterol (78) was achieved through a photochemical
reaction with lead tetraacetate and iodine. This successful interconversion
confirmed all structural features of seychellogenin (73a) and by extension of
all other known holothurinogenins with exception of the configuration at
C-20. Stereochemistry at C-20 was still in doubt since the degradation of 73a
destroyed the chirality when the ring-opened triol was dehydrated. Hydrogénation of the A
20
'
21
-olefin led to a mixture of epimers which was subsequently separated, and the epimer which had the lanosterol stereochemistry
at C-20 was utilized.
The inconsistency of the ultraviolet spectral properties of the natural
glycosides (no absorption beyond 212 nm) when compared with the holothurinogenins (triple band centered at 244 nm characteristic of a heteroannular diene) had made it clear at the outset of these investigations that the
structure of the holothurinogenins could not be the structure of the intact
triterpenoid glycosides prior to acid hydrolysis. Obviously the heteroannular
diene system was generated in the course of the acid treatment, but the lactone function and the 22,25-oxide bridge were also suspect as potential
artifacts that had arisen during hydrolysis. Chanley and Rossi (1969a,b)
resolved these points of uncertainty in the following manner. When holothurin A—the crude glycosidic mixture—was hydrolyzed in 0.2 Ν hydrochloric acid in methanol at 50°, hydrolysis was complete after 76 hours
without significant generation of the diene chromophore. The resulting
aglycones were a mixture of mono- and dimethoxy
fleo-holothurinogenins,
which by the conventional strong acid treatment could be converted to the
known holothurinogenins.
Holothurin A, the mixture of natural glycosides, contains only one methoxy
group as 3-methoxy-D-glucose. The methoxy group(s) of the weo-holothurinogenins must therefore have arisen as a result of methanolysis. By careful
spectral analysis the structures of the neo compounds were shown to be 79a,
79b, 80, 81, and the dimethoxy compound 82. Compound 80 represented the
precursor of griseogenin (69), whereas compound 81 exhibited a new side
chain. Compound 81 on strong acid treatment was converted to the corresponding A
24
'
25
-holothurinogenin, which also was the compound into which
the dimethoxy-weo-holothurinogenin 82 was transformed. Chanley and Rossi
(1969a) further demonstrated that the 22,25-oxido side chain in compounds
63a and b was a naturally occurring structural feature and that the 25methoxy group of 82 was generated from a precursor with a 24,25-double
bond (81).
The 12-methoxy group that was common to all neo compounds most
likely resulted from an allylic 12-hydroxy group. This supposition was con-
/. Isoprenoids
holothurinogenin was seychellogenin (73a). It was chosen for degradation to
an intermediate 77 that was also prepared from lansterol (78). The functionalization of C-18 of lansterol (78) was achieved through a photochemical
reaction with lead tetraacetate and iodine. This successful interconversion
confirmed all structural features of seychellogenin (73a) and by extension of
all other known holothurinogenins with exception of the configuration at
C-20. Stereochemistry at C-20 was still in doubt since the degradation of 73a
destroyed the chirality when the ring-opened triol was dehydrated. Hydrogénation of the A
20
'
21
-olefin led to a mixture of epimers which was subsequently separated, and the epimer which had the lanosterol stereochemistry
at C-20 was utilized.
The inconsistency of the ultraviolet spectral properties of the natural
glycosides (no absorption beyond 212 nm) when compared with the holothurinogenins (triple band centered at 244 nm characteristic of a heteroannular diene) had made it clear at the outset of these investigations that the
structure of the holothurinogenins could not be the structure of the intact
triterpenoid glycosides prior to acid hydrolysis. Obviously the heteroannular
diene system was generated in the course of the acid treatment, but the lactone function and the 22,25-oxide bridge were also suspect as potential
artifacts that had arisen during hydrolysis. Chanley and Rossi (1969a,b)
resolved these points of uncertainty in the following manner. When holothurin A—the crude glycosidic mixture—was hydrolyzed in 0.2 Ν hydrochloric acid in methanol at 50°, hydrolysis was complete after 76 hours
without significant generation of the diene chromophore. The resulting
aglycones were a mixture of mono- and dimethoxy
fleo-holothurinogenins,
which by the conventional strong acid treatment could be converted to the
known holothurinogenins.
Holothurin A, the mixture of natural glycosides, contains only one methoxy
group as 3-methoxy-D-glucose. The methoxy group(s) of the weo-holothurinogenins must therefore have arisen as a result of methanolysis. By careful
spectral analysis the structures of the neo compounds were shown to be 79a,
79b, 80, 81, and the dimethoxy compound 82. Compound 80 represented the
precursor of griseogenin (69), whereas compound 81 exhibited a new side
chain. Compound 81 on strong acid treatment was converted to the corresponding A
24
'
25
-holothurinogenin, which also was the compound into which
the dimethoxy-weo-holothurinogenin 82 was transformed. Chanley and Rossi
(1969a) further demonstrated that the 22,25-oxido side chain in compounds
63a and b was a naturally occurring structural feature and that the 25methoxy group of 82 was generated from a precursor with a 24,25-double
bond (81).
The 12-methoxy group that was common to all neo compounds most
likely resulted from an allylic 12-hydroxy group. This supposition was con-