Cephaelin

Cephaeline (hRf 40 — 45) produces a blue color spontaneously immediately on immersion, while emetine (hRf 60—65) only does so on heating on storage this color slowly changes to brown (background hght brown). The detection limits for both substances are ca. 10 ng per chromatogram zone. 

Fig. 1 Absorption scans of the pure substances (ca. 500 ng of each) cephaeline and emetine (A) and an extract of Ipecacuanhae Radix (B) cephaeline (1), emetine (2).

The roots of Cephcelis Ipecacuanha (Brot) A. Rich constitute the Brazilian ipecacuanha of commerce and also that cultivated in the Federated Malay States, Bengal and Burma. Carthagena ipecacuanha is derived from Cephcelis acuminata Karsten collected in Colombia. Emetine, the principal alkaloid of this drug, was first obtained by Pelletier and Magendie in 1817, but was first prepared in a pure state by Paul and Cownley, who separated from commercial emetine the phenolic base, cephaeline, and later obtained a third alkaloid, psychotrine. To these Pyman added emetamine and 0-methylpsychotrine. 

Processes for the extraction of the total alkaloids and isolation of the-individual bases will be found in the papers cited above. Cephaeline is too toxic for medical use and is usually converted into emetine by methyla-tion of the phenolic hydroxyl group, and processes have been patented for this purpose, beginning with that of Wellcome, Carr and Pyman in 1913. ... 

Methylation of the Alkaloids. When cephaeline is treated with methyl sulphate or sodium methyl sulphate under various condition, there is formed in addition to emetine (which was first shown to be the methyl ether of cephaeline and partially synthesised in this way by Carr and Pyman in 1913), more or less N-mcthylcephaeline (wedge-shaped plates, m.p. 194 5°), and N-methylemetine. The latter is also obtained by direct methylation of emetine it is amorphous, [a]n — 52-6° (CHCI3), but yields a hydrobromide, C33H42O4N2.2HBr. 3H2O, m.p. 210-30°, [ajp + 5-6° (H2O). 

The relationship of psychotrinc and 0-methylpsychotrine to the two pairs of stereoisomerides a) cephaeline -j- tsocephaeline, and (b) emetine + isoemetine respectively, implies that in each of these reductions one ethylenic linkage is saturated and produces one new centre of asymmetry. This ethylenic linkage is assumed to he at to C , so that on this basis the components of each of the stereoisomeric pairs a) and (b) just referred to must he epimeric pairs about C. ... 

Emetine, cephaeline Silica gel 60 After iodine treatment emetine fluoresces yellow and cephaeline blue [17]... 

The chromatograms are freed from mobile phase in a stream of warm air, inunersed in the dipping solution for 3 s or homogeneously sprayed with the spray solution. Only in exceptional cases, such as, for example, in the detection of emetine and cephaeline, are the chromatograms then heated to 60-80°C for 10-20 min [15, 16, 31]. 

The detection limits are mostly in the microgram range, for cephaeline and emetine they are 200 pg substance per chromatogram zone. 

Cephaeline (h/ f 6-11) appeared as blue and emetine (h/ f 10-15) as yellow fluorescent chromatogram zones on a dark background when examined under long-wavelength UV light (X. = 365 nm) (Fig. 1). Emetine — like cephaeline — also yielded a blue fluorescence on RP-2 and RP-18 layers. 

Note Under the conditions employed emetine and cephaeline were not well separated but there was good resolution of the subsidiary alkaloids of the ipecacuanha tincture (Fig. 1). The separation and quantitative determination of the main alkaloids (Fig. 2) can be carried out under the following conditions Ascending, one-dimensional development in a trough chamber with chamber saturation layer HPTLC plates Silica gel 60 (Merck) mobile phase dichloromethane — methanol — ammonia solution (25%) (34+6+1) migration distance 6 cm running time 13 min h/ f cephaeline 65-70 emetine 75-80. 

Fig. 1 Chromatogram of ipecacuahna tincture and of the standard substances 1 = emetine, 2 = tincture, 3 = cephaeline.

Fig. 2 Fluorescence scan of the chromatogram tracks of the standard substances cephaeline (A) and emetine (B) and of the ipecacuanha extract (C). Amounts applied cephaeline 0.5 pg, emetine 0.7 pg per 10 mm track length.

From dopamine, the pathway of tetrahydroisoquinoline alkaloids, such as emetine and cephaeline (Figure 37), also begins. Dopamine and secologanin undergo a Mannich-like to produce A-deacetylisoipecoside and ipecoside, and after hydrolysis and transformation, this is converted to emetine and cephaeline. 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

---