Tetrahydroisoquinoline alkaloid

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. 

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

Terpenoid tetrahydroisoquinoline alkaloids 110 Terretonin 41, 56 Territrem A 43, 56 Territrem B 43, 56 Tetracyclic alkaloids 88, 100 Tetracyclic quinolizidine alkaloids 100, 101 Tetrahydroharman 59 Tetrahydroharmine 80, 112, 114 Tetrahydroisoquinoline alkaloids 7, 58, 68, 77, 78... 

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... 

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 knowledge of the emetine fragmentation pattern proved very helpful in the structure elucidation of the unknown alkaloid tubulo-sine.85 Mass spectrometry aided very much in solving the structural problem of rhoeadine, first thought to be a tetrahydroisoquinoline alkaloid but now shown to be a representative of a new alkaloid... 

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.

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