Simple tetrahydroisoquinoline alkaloids

Simple indole alkaloids 8, 111, 112, 113 Simple phenylamine alkaloids 110 Simple tetrahydroisoquinoline alkaloids 7,... 

Mammalian isoquinoline alkaloids include simple tetrahydroisoquinolines, catecholic congeners such as salsolinol and its methyl ether analogs,... 

Kametani, T., Honda, T Fukumoto, K., Toyota, M., lhara, M. Synthetic approach to diterpene alkaloids - a simple and novel synthesis of the A,B,C and D ring part from 1-benzyl-1,2,3,4-tetrahydroisoquinoline. Heterocycles 1981, 16, 1673-1676. 

For a simple specific example, the tetrahydroisoquinoline alkaloid salsolinol is found in some plants, and it can also be detected in the urine of humans as a product from dopamine and acetaldehyde. 

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. 

Closely-related alkaloids cooccurring with mescaline are anhalamine, anhalonine, and anhalonidine (Figure 6.40), which are representatives of simple tetrahydroisoquinoline derivatives. 

The mammalian isoquinolines so far detected and characterized are shown in Figs. 28 and 29. Tetrahydroisoquinoline (117) and its 1-methyl congener TIQ 118a were found in rat brain (181) and in food (182). TIQ 117 produces a Parkinson-like syndrome in rats, and the levels of dopamine were markedly decreased (168). GC-MS techniques and chiral reagents identified the major alkaloid present in animal tissue as the (5)-configured TIQ 118a (183,184). The 4-hydroxy-substituted TIQ 79, detected in rat liver and in rat urine (163), is probably the most interesting of the simple mammalian TIQs, and its relevance to MPTP in parkinsonism was mentioned earlier. 

The isoquinoline alkaloids are the second largest group of alkaloids, numbering about 6000, and can be viewed as five subgroups—the simple tetrahydroisoquinolines, the benzylisoquinolines, the phenethylisoquinolines, the Amaryllidaceae alkaloids, and the monoterpene isoquinolines. In addition, there are a number of simple phenethylamine derivatives, including ephedrine (originally from Ephedra species, but now synthesized) and pseudoephedrine, used for asthma and nasal... 

Synthetic approaches to carnegine, a simple tetrahydroisoquinoline alkaloid 04T10575. 

The range of simple isoquinoline alkaloids, principally obtained from cacti, has recently been greatly expanded by the isolation of isoquinolines, 3,4-dihydroisoquinolines and 1,2,3,4-tetrahydroisoquinolines bearing one, two, three and... 

The presently known cactus alkaloids are of simple chemical constitution. They are either substituted /3-phenethylamines, evidently related to and probably derived from the naturally occurring aromatic amino acids (tyrosine, dihydroxyphenylalanine, A -methyltyrosine, etc.), or they are simple tetrahydroisoquinolines that could originate from these bases by condensation and cyclization through the action of organic compounds containing one or two carbon atoms (formaldehyde and acetaldehyde equivalents ). 

Alkaloids can be divided into different t q3es according their pure chemical structures pointing first at the alkaloid base, a basic chemical nucleus. The following are basic types of alkaloids acridones, aromatics, carbo-lines, ephedras, ergots, imidazoles, indoles, bisindoles, indolizidines, manza-mines, oxindoles, quinolines, quinozolines. quinolizidines, phenylisoquinolines, phenylethylamines, piperidines, purines, pyrolidines, pyrrolizidines, pyrro-loindoles, pyrydines, sesquiterpenes, simple tetrahydroisoquinolines, stereoids, tropanes, terpenoids, diterpenes, and triterpenes. 

The second synthesis pathway from L-tyrosine is to dopamine across hydro-xylation patterns and PLP activity. Dopamine is a very important compound in the synthesis of alkaloids, especially in animals. Only dopamine can be converted to another alkaloid, for example, mescaline. Anhalamine, anha-lonine, and anhalonidine can also be synthesized in this way. Like mescaline, they are typical of simple tetrahydroisoquinoline alkaloids. 

Salsola alkaloids a group of simple isoquinoline alkaloids, occurring in Isola spp. Chief representative is salsoline (l-methyl- hydroxy-7-methoxy-1,23,4-tetrahydroisoquinoline), which occurs in the D-form, m.p. 215-216°C, [a]p + 40° (water) and in the DL-form. 

The recent isolation of a series of simple tetrahydroisoquinoline alkaloids monooxygenated in ring A, such as longimammatine and longimammidine, raises interesting and still unanswered questions concerning their biogenesis. ... 

Alkaloids derived from tyrosine include phenylethylamine alkaloids, simple tetrahydroisoquinoline alkaloids, and modified benzyl tetrahydroisoquinoline alkaloids. The chemistry of Erythrina and related alkaloids from 1996 to mid-2009 has been reviewed, with a particular focus on the preparation of Erythrina alkaloids possessing an aromatic D ring [13]. 

The Chenopodiaceae family is closely related to the Cactaceae, both belonging to the order of Caryophyllales. Four species of this family are known to contain simple tetrahydroisoquinoline alkaloids of the same kind as found in cactus species (Table 3). Salsola arbuscula was the first known natural source of salsoline and salsoUdine (Orekhov and Proskumina 1934). No phenethylamine derivatives are reported from the Chenopodiaceae species containing tetrahydroisoquinolines. However, another species of this family, Haloxylon salicornum (Moq.-Tand.) Boiss. is rich in substituted phenethylamines (Michel and Sandberg 1968) which further points at the close relationship with the Cactaceae family. 

Three 3-carboxyl substituted simple tetrahydroisoquinoline alkaloids are known from natural sources (Table 5). The compound found in Euphorbia myrsinites has been shown to originate from m-tyrosine (Muller and Schutte 1971). 

In collaboration with Dr. Margaret Roberts of the University of London, we recently learned that latex also contains miUimolar concentrations of dopamine, a fraction of which occurs in the same, relatively dense vacuoles that are rich in alkaloids (Roberts et al. 1983). Dopamine is an essential intermediate in the biogenesis of the alkaloids of the Papaveraceae (Shamma and Moniot 1978, Spenser 1969). Dopamine, which is formed from tyrosine, condenses with different carbonyl derivatives in Pic-tet-Spengler reactions to afford simple tetrahydroisoquinolines that can then give rise to a diverse array of alkaloids. Considerable evidence exists to suggest that the chirality of the tetrahydroisoquinoline alkaloids influences their transformation. It appears that morphinan alkaloids are formed from (-)-R-reticuline, whereas most other alkaloids including sanguinarine are derived from (+)-S-reticuline (Battersby et al 1965, 1975, Wilson and Coscia 1975, Borkowski et al. 1978, Brossi 1982). 

Simple tetrahydroisoquinoline alkaloids are obtained upon condensation of phenylethylamines and catecholamines with carbonyl compounds. In a subsequent Mannich-hke reaction, the biosynthetic equivalent to a Pictet-Spengler reaction, the heterocyclic ring system is established. Numerous examples of simple tetrahydroisoquinoline alkaloids have been isolated from different plant sources. Several of these tyrosine-derived secondary metabolites exhibit intriguing biological and physiological properties, due to their structural relationship to catecholamines and phenylethylamines. 

The condensation of dopamine (4) with phenylethyl units and subsequent cyclization result in the formation of benzyltetrahydroisoquinoline alkaloids. These initial reaction steps are identical to those discussed for the formation of simple tetrahydroisoquinoline alkaloids. However, the additional aromatic ring allows further modification, and a variety of structurally diverse classes of alkaloids are obtained via different aryl-aryl coupling reactions. Among others, protoberberine alkaloids, porphine alkaloids, and the most important class of opium alkaloids can be summarized as modified benzyltetrahydroisoquinoline alkaloids. 

---