YOHIMBINE (Quebrachine)

Description

The major alkaloid of the bark of Pausinystalia yohimba (Syn. Corynanthe yohimbe), this base has also been isolated from P. macroceras, P. paniculata and P. trillesii. The alkaloid crystallizes from dilute EtOH in colourless needles and various specific rotations have been recorded: [α]^{20/sup>_D + 107.9° (pyridine); + 56° (EtOH) according to Fourneau or + 62.2° (EtOH) according to Witkop. It is freely soluble in EtOH or CHCl3 but only sparingly so in Et20. It is almost insoluble in H2O. Under vacuum, the base sublimes at 159°C/0.01 mm. The salts are well crystalline and include the hydrochloride, colourless plates, m.p. 300-2°C; [α]22/sup>_D + 103.3° (H2O); the nitrate, m.p. 269-2700 C; tartrate hexahydrate, m.p. 213°C, followed by solidification and remelting at 278°C; thiocyanate, rectangular crystals, m.p. 233-4°C and the methiodide, colourless plates from Me2CO, m.p. 249-250°C. On acetylation, the alkaloid furnishes the Q-acetate, m.p. 133°C and the O,N-diacetyl derivative, m.p. 183°C.
When heated with KOH solution, followed by acidification with AcOH, the alkaloid gives MeOH and yohimbic acid, C20H2403N2 which crystallizes as the monohydrate, m.p. 265-9°C or 299°C (dry, dec.); [α]20/sup>_D + 138.8° (pyridine). The latter yields a series of esters; the ethyl ester having m.p. 190°C; [α]D + 95° (pyridine) or + 45.2° (EtOH); propyl ester, m.p. 137°C as the monohydrate; butyl ester monohydrate, m.p. 119-122°C or 127°C (dry) and the benzyl ester, which is amorphous, m.p. 77-8°C.
Yohimbine possesses local anaesthetic properties, resembles ergotamine in its sympatholytic action, lowers the blood pressure and increases the depth and frequency of respiratory movements. In toxic doses, death in mammals is due to respiratory paralysis, the heart being active for some time longer. As a vasodilator, yohimbine is the most potent of this group of alkaloids and it finds its principal use as an aphrodesiac in veterinary medicine. The diacetyl derivative is aseffective as the free base as a vasodilator but somewhat less toxic.}

References

Spiegel., Chem. Zeit., 20, 970 (1896) Thoms., Ber. Deut. pharm. Ges., 7,279 (1897) Spiegel., Ber., 36, 169 (1903) Herzog., Ber. Deut. pharm. Ges., 15,4 (1905) Herzog., Pharm. Zeit., 48,967,983 (1908) Fourneau, Page., Bull. Sci. Pharmacol., 21,7 (1914) Field.,J. Chem. Soc., 123, 3003 (1923) Feldhoff., Pharm. Zeit., 70, 864 (1925) Schomer., Chem. Zentr., 11,2309 (1927) Warnat., Ber., 63, 2959 (1930) Rossi et al., Ann. Farm. Bioquim., 3, 51 (1932) Witkop., Annalen, 554, 83, 127 (1943) Clemo, Swan., J. Chern. Soc., 617 (1946) Clemo, Swan., ibid, 487 (1949) van Tamelen et aI., J. A mer. Chern. Soc., 80,5006 (1958) Pharmacology : Muller., Arch. into Pharmacodyn., 17,81 (1902) Raymond-Hamet., Compt. rend., 180,2074 (1925) Hesse, Langer., Med. Klinik., 27,1536(1931) Rothlin, Raymond-Hamet., Arch. into Pharmacodyn., 50,241 (1935) Rothlin, Raymond-Hamet., Arch. expo Path. Pharm., 178, 305 (1935)