SINOMENINE (Cuculine)

Description

This alkaloid was first isolated by Ishiwari from Sinorneniurn acuturn Rehd. and Wils. It crystallizes from C6H6 in stellate groups of needles and has two melting points. The specific rotation is[α]²⁶_D - 70.76° (EtOH). The alkaloid is insoluble in petroleum ether, sparingly so in H₂0, more soluble in CHCI₃, EtOH, pentanol and Me₂CO. The following salts and derivatives have been prepared: the hydrochloride, m.p. 231°C;[α]¹⁷_D- 82.4° (H₂0); hydrobromide, m.p. 231°C; hydriodide, m.p. 233°C; nitrate, m.p. 215°C (dec.); picrate, m.p. l35-142°C; oxime, m.p. 233°C; methiodide, decomposing at 255°C; benzoyl derivative, m.p. 225°C and the O-methyl ether, m.p. 175°C. A crystalline semicarbazone, m.p. 264°C has also been prepared. On catalytic hydrogenation, the base forms the dihydro derivative as colourless needles, m.p. 199°C;[α]¹⁶_D+ 170.5°. Distillation with Zn dust furnishes trimethylamine and phenanthrene and when heated with KOH solution, sinomenol, m.p. 176°C is produced.
The pharmacological properties of sinomenine and its derivatives have received a good deal of attention from Japanese workers. Goto and Takebe have shown that the dextrorotatory derivatives are convulsive poisons and do not show either the analgesic or sedative actions characteristic of (-)-morphine derivatives. The free alkaloid produces increased reflex excitability and respiratory paralysis in mice, frogs and rabbits. In mice, these symptoms are also accompanied by a vasodilatation in the vessels of the skin and mucosae. Small doses stimulate while larger doses first stimulate and then paralyse the plain muscle of the uterus and intestine.

References

Ishiwari., Chern. Soc., Abstr., i, 354 (1921)
Goto., Proc. Imp. A cad. Tokyo, 2,7,167,414 (1926)
Kondo, Ochiai., J. Pharm. Soc., Japan, No. 538, 1008 (1926)
Kondo, Ochiai., ibid, 49,556 (1929)
Kondo, Ochiai., Annalen, 470, 224 (1929)
Goto, Sudzuki., Bull. Chem. Soc., Japan, 4, 244 (1929)
Goto, Michinaki, Shishido., Annalen, 515, 297 (1935)
Pharmacology:
Goto, Takebe., Proc. Imp. A cad. Tokyo, 9, 390 (1933)
Takaori., Deut. med. Woch., 62, 1634 (1936)
Rin., Proc. Jap. Pharm. Soc., 12, 194 (1938)