Chemical Properties
White Solid
Uses
It is useful as signal transduction inhibitor for treating tumors
Definition
ChEBI: A piperidine alkaloid comprising the 14,15,16,17-tetradehydro derivative of veratraman having two hydroxy groups at the 3- and 23-positions.
Uses
The hedgehog (Hh) signaling pathway, which is blocked by cyclopamine , plays a key role in morphogenesis and has potential applications in the treatment of cancer. Veratramine, a teratogenic steroidal alkaloid isolated from the corn lily (Veratrum sp.), is an analog of cyclopamine that can inhibit the Hh signaling-dependent proliferation of NIH/3T3 cells at 8 μM. Additionally, veratramine has anti-thrombotic activity as it dose dependently inhibits platelet aggregation in rabbits ex vivo. While it may be most useful as a signal transduction inhibitor for treating tumors, veratramine also induces serotonin release and inhibits its re-uptake in the CNS.
Description
This alkaloid occurs naturally in Veratrum grandi/lorum and V. viride and is
also formed during the hydrolysis of Veratrosine (q.v.). It forms colourless
crystals of the monohydrate from aqueous EtOH and has [α]19D - 70° (MeOH).
The hydrochloride forms colourless plates from EtOH, m.p. 20l-2°C and the
picrate, yellow plates, m.p. 217.5 - 218°C. Two non-phenolic hydroxyl groups
and an imino group are present and the triacetyl derivative, m.p. 205.5-206°C;
[α]14.5D + 37.8° (MeOH), on controlled hydrolysis furnishes the N-acetyl com_x0002_pound, m.p. 176-8°C. The O-acetate has also been prepared as colourless prisms
from aqueous EtOH, m.p. 20l-2°C but it is still uncertain which of the hydroxyl
groups is acetylated in this derivative. Treatment with methyl iodide in MeOH in
the presence of sodium carbonate gives N-methylveratraminc methiodide, m.p.
268°C (dec.) from which the methochloride, m.p. 277°C can be obtained. On
catalytic hydrogenation, the base furnishes the dihydro derivative, m.p. 198-
200°C; [α]27D + 27.4°, which forms the N-acetyl compound, m.p. 220-3°C;
[α]28D + 81° and the triacetyl derivative, m.p. l89.5-190.5°C; [α]24D + 84°.
References
Saito., Bull. Chem. Soc., Japan, 15, 22 (1940)
Jacobs, Craig.,J. Biol. Chem., 155,565 (1944)
Jacobs,.Craig., ibid, 160,555 (1945)
Tamm, Wintersteiner., J. Amer. Chem. Soc., 74,3842 (1952)
Mass spectra:
Budzikiwicz., Tetrahedron, 20,2267 (1964)
Synthesis:
Masamune, Takasugi, Murai., Tetrahedron, 27,3369 (1971)
