Tetrahydroisoquinoline alkaloids, and

Padwa and co-workers (232,233) adapted their thioisomiinchnone generation-cycloaddition strategy to the synthesis of several tetrahydroisoquinoline alkaloids and the indolo[2,3-a]quinolizidine alkaloid alloyohimbane 333 (Scheme 10.44). 

Carbon-13 n.m.r. spectroscopy has been used to study benzylisoquinoline and tetrahydroisoquinoline alkaloids and their JV-methyl quaternary salts.30 N-Benzylpapaverinium bromide has been shown to undergo aerial oxidation in alkaline solution to 2-benzyl-6,7-dimethoxyisoquinolone and to give bases of general structure (10) with methylamine, benzylamine, and pyrrolidine.31 Chlorosulphonation of papaverinol affords the sulphonic acid ester (11), mild hydrolysis of which yields the acid (12), which with diazomethane is esterified and dehydrated to (13).32 N-Methyl-l,2-dihydropapaverine has been shown by kinetic studies and orbital-symmetry requirements to rearrange to the salt (14) by the route previously postulated.33... 

Tetrahydroisoquinoline alkaloids and 2-deoxyribonolactones from Aristolochia arcuata. Lopes and co-workers made use of long-range HMBC data in... 

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]. 

Zhou YD et al (2005) Terpenoid tetrahydroisoquinoline alkaloids emetine, king me. and isocephae-line inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells. J Nat Prod 68(6) 947-950... 

Cawe (Pachycereus pecten-aboriginum) is yet another species of hallucinogenic cactus, which grows in Mexico. It is also a columnar cactus, growing up to 35 feet in height. It is known as Cawe or Wichowaka to the Tarahumara. Studies have identfied 4-hydroxy-3-methoxyphenylethylamine and 4-tetrahydroisoquinoline alkaloids as the probable psychoactive constituents. 

Trabectedin (36 Yondelis, ecteinascidin-743, ET-743 Zelfia and Johnson and Johnson, 2007), a tetrahydroisoquinoline alkaloid produced hy the ascidian Ecteinascidia turbinate,received approval for its sale in Europe, Russia and South Korea by Zelfia and Johnson and Johnson under the brand name YondelisT for the treatment of advanced soft tissue sarcoma (STS). Trabectedin (36) binds to the minor groove of DNA and inhibits cell proliferation by disrupting the cell cycle. 

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. 

In Box 9.4, we saw that tetrahydroisoquinoline alkaloids with appropriate phenol substituents could be involved in radical coupling processes. The complex alkaloids tubocurarine and morphine are derived in nature from simpler tetrahydroisoquinoline alkaloids. 

Intramolecular Sn2 reactions of lactams 376 and 377 (see Scheme 85, lower part) produced nitrogen- and oxygen-bridged, highly strained products 378, 379, and 380, forming densely functionalized tetracyclic frameworks of the tetrahydroisoquinoline alkaloids (08TL5141). 

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. 

Desai, and S. S. Hecht. Evidence for endogenous formation of tobacco—specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite. Carcinogenesis 1997 18(3) 587—592. NT257 Mendez-Alvarez, E., R. Soto-Otero, I. Sanchez-Sellero, and M. Lopez-Ri-vadulla Lamas. Inhibition of brain monoamine oxidase by adducts of 1, 2,3,4-tetrahydroisoquinoline with components of cigarette smoke. Life Sci 1997 60(19) 1719-1727. 

The 1.2.3.4-tetrahydroisoquinoline skeleton represents the framework found in many isoquinoline alkaloid derivatives and not only from plants. Some derivatives attracted much interest because of their anti-cancer activity [124], which has prompted many groups to invest in their chemical synthesis. The Pictet-Spengler reaction has become an important method in the preparation of this alkaloid type, and has often been described with phenylalanine derivatives and pyruvates as starting materials. Synthesis of appropriate tetrahydroisoquinoline-3 and the corresponding tetrahydroisoquinoline-1-carboxylic acid has been the key target [125]. 

Bishay and co-workers (5) postulated a possible correlation between cyclopeptide and tetrahydroisoquinoline alkaloids when they isolated R-( — )-armepavine as well as franguline-type bases from Euonymus europaeus. Pailer and Haslinger (45) isolated, in addition to the known peptide alkaloids, the same armepavine during a renewed examination of Rhamnus frangula. 

Kong, F., Harper, M. K., and Faulkner, D. J., Fuscusine, a tetrahydroisoquinoline alkaloid from the sea star Perknaster fuscus antarcticus, Nat. Prod. Lett., 1, 71, 1992. 

The aromatic, tetramethoxy-substituted, tetrahydroisoquinoline alkaloid weberine has been isolated recently from extracts of the Mexican cactus Pachycereus weberi (38). The rare occurrence of four adjacent methoxy groups on an aryl moiety prompted the synthesis and examination by crystal-structure analyses of analogs and derivatives with four and five adjacent methoxy groups on the phenyl ring. In contrast to the problem with... 

A reversed phase HPLC-APCI-MS/MS method was developed to analyze filtered methanolic extracts of plant samples for the presence of the tetrahydroisoquinoline alkaloids tetrandrine and fangchinoline (Figure 13.4). In this way it was clearly shown that 9 of 10 samples purported to be S. tetrandra were in fact the toxic substituent Aristolochiafangchi whilst the tenth sample was unidentified but also unrelated to S. tetrandra [17]. 

Fig. 13.4 The tetrahydroisoquinoline alkaloids tetrandrine and fangchinoline extracted from Stephania tetrandra and analyzed using HPLC-APCI-MS/MS.

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. 

Stadler, R. and Zenk, M.H. (1990) A revision of the generally accepted pathway for the biosynthesis of tetrahydroisoquinoline alkaloid reticuline. Liebigs Ann. Chem., 555-62. 

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