Psychotrine

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. 

Alangium lamarckii Lour. dl-Anabasine, cephaeline, emetine, psychotrine, tubulosine, ankorine isotubulosine, demethyl-tubulosine, demethylpsychotrin, alangicine, deoxytubulosine, alangimarckine, alamarchine, demethylcephaeline.33 ... 

Ipecac contains 2-2.5% of alkaloids, the principal ones being emetine and cephaeline (Figure 6.67). Typically, in C. ipecacuanha the emetine to cephaeline ratio might be about 2 1, whereas in C. acuminata the ratio ranges from about 1 2 to 1 1. Minor alkaloids characterized include psychotrine and O-methylpsychotrine (Figure 6.68), which are dehydro variants of cephaeline and emetine respectively. 

AVAROL, AVARONE, PSYCHOTRINE, AND PHLOROGLUCINOL DERIVATIVES (i.e., MALLOTOJAPONIN)... 

Ipecac is the root of Cephaetis ipecacuanha, or of C. acuminata, a perennial shrub growing in Brazil and other South American states (Figure 44.1). It contains three alkaloids — emetin, cephaelin, and psychotrin. The dose of the powdered drug as an expectorant is from 1/2 to 2 grain (0.03 to 0.13 g) as an emetic, 15 to 30 grain (1.0 to 2.0 g) (Table 44.1). 

Emetine was first described in 1817 by Pelletier, the discoverer of quinine. However, Pelletier was actually dealing with a mixture of the alkaloids of ipecac, that is, emetine, cephaeline, and psychotrine (see Grollman, 1962). 

Compounds of the emetine class containing a double bond in ring D, e.g., psychotrine (174), are cleaved by a McLafferty rearrangement. The primary degradation product [175] can easily lose the side chain, producing an allylic carbonium ion [176].84... 

Cephaeline (2), psychotrine (6), ankorine (13), venoterpine (25), and ( )-anabasine (28) have also been found in some other species of Alangium (18,19) and the alkaloid, C28H35N303 [mp200°C [ ] —40° (pyridine)], in the bark of A. vitiense (20). It is interesting to note that emetine (1) has been isolated from Hedera helix L. (family Araliaceae) (21,22). 

Psychotrine (6) has already been synthesized by condensation of the (—)-tricyclic ester 29 with 3-benzyloxy-4-methoxyphenethylamine, followed by Bischler-Napieralski cyclization and debenzylation (76). Thus, the syntheses of (—)-29 reviewed last in Section III,B constitute formal syntheses of this alkaloid. 

In the early work (93) summarized in Chapter 3 of Volume XIII (3), two alternative structures 8 and 93 were considered for (+)-demethylpsycho-trine on the basis of its conversion to O-methylpsychotrine (7) and its formation from psychotrine (6) by acid hydrolysis and from the mass spectral evidence. The structure of (-l-)-demethylpsychotrine has now been established as 8 as a result of the syntheses of ( )-9-demethylpsychotrine (8), ( )-10-demethylpsychotrine (93), and (+)-9-demethylpsychotrine (8) by Fujii et al. (94,95). The syntheses of ( )-8 and ( )-93 (94) consisted of initial... 

No direct evidence has been presented for the position of the double bond in the dihydroisoquinoline moiety of psychotrine, demethylpsychotrine, and alangicine. However, Fujii et al. (89) considered the double bond to be endocyclic, as shown in formulas 6, 8, and 9, analogous to that established for O-methylpsychotrine (7). 

Although known synthetically for a long time (1,14), (—)-isocephaeline (3) was not encountered in nature until quite recently. In 1980, Pakrashi s group (5) isolated this (—) base from the seeds of Alangium lamarckii Thw. and confirmed its identity with authentic isocephaeline prepared by NaBH4 reduction of psychotrine (6). 

Emetine in A Emetine in B Cephaeline in A Cephaeline in B Psychotrine in A Alkaloids in A Ipecac alkaloids in B Emetine Emetine in A Emetine in B Emetine in C Cephaeline Cephaeline in A Cephaeline in B Emetine Emetine Emetine in B Ipecac alkaloids in B Emetine Emetine in A Emetine in B Cephaeline Emetine Emetine in A Emetine in B Cephaeline in A Emetine Emetine in B Emetine in C Cephaeline... 

The root of the ipecac is commonly used as an expectorant in the treatment of bronchitis, croup, asthma amoebacide and whooping cough, as an emetic in cases of poisoning, and an amoebacide in amoebic dysentery. It has appeared in the Japanese Pharmacopoeia (2001) as ipecac, powdered ipecac and ipecac S)nxip [6]. The ipecac is rich in isoquinoline alkaloids such as emetine, cephaeline, psychotrine. 

Fig. (2). The structures of emetine (1), cephaeline (2), psychotrine (3), O-methylpsychotrine (4), emetamine (5), protoemetine (6)...

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