85-64-3Relevant articles and documents
Studies on tetrahydroisoquinolines XXVIII. Syntheses of (±)-N-methyllaurotetanine (±)-cassythicine, (±)-9-hydroxy-1,2,3,10-tetramethoxyaporphine, (±)-dicentrine, and (±)-thalicisimidine
Hara,Hashimoto,Hoshino,Umezawa
, p. 1946 - 1949 (1986)
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The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet-Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids
Bartel, Karin,Bracher, Franz,Geisslinger, Franz,Keller, Marco,Sauvageot-Witzku, Karl,Schaefer, Michael,Urban, Nicole
, p. 2716 - 2725 (2022/01/12)
We present a systematic investigation on an improved variant of the N-acyl-Pictet-Spengler condensation for the synthesis of 1-benzyltetrahydroisoquinolines, based on our recently published synthesis of N-methylcoclaurine, exemplified by the total syntheses of 10 alkaloids in racemic form. Major advantages are a) using ω-methoxystyrenes as convenient alternatives to arylacetaldehydes, and b) using the ethoxycarbonyl residue for both activating the arylethylamine precursors for the cyclization reaction, and, as a significant extension, also as protective group for phenolic residues. After ring closure, the ethoxycarbonyl-protected phenols are deprotected simultaneously with the further processing of the carbamate group, either following route A (lithium alanate reduction) to give N-methylated phenolic products, or following route B (treatment with excess methyllithium) to give the corresponding alkaloids with free N-H function. This dual use of the ethoxycarbonyl group shortens the synthetic routes to hydroxylated 1-benzyltetrahydroisoquinolines significantly. Not surprisingly, these ten alkaloids did not show noteworthy effects on TPC2 cation channels and the tumor cell line VCR-R CEM, and did not exhibit P-glycoprotein blocking activity. But due to their free phenolic groups they can serve as valuable intermediates for novel derivatives addressing all of these targets, based on previous evidence for structure-activity relationships in this chemotype.
Three new O-methyltransferases are sufficient for all O-methylation reactions of ipecac alkaloid biosynthesis in root culture of Psychotria ipecacuanha
Nomura, Taiji,Kutchan, Toni M.
experimental part, p. 7722 - 7738 (2011/03/18)
The medicinal plant Psychotria ipecacuanha produces ipecac alkaloids, a series of monoterpenoid-isoquinoline alkaloids such as emetine and cephaeline, whose biosynthesis derives from condensation of dopamine and secologanin. Here, we identified three cDNAs, IpeOMT1-IpeOMT3, encoding ipecac alkaloid O-methyltransferases (OMTs) from P. ipecacuanha. They were coordinately transcribed with the recently identified ipecac alkaloid β-glucosidase Ipeglu1. Their amino acid sequences were closely related to each other and rather to the flavonoid OMTs than to the OMTs involved in benzylisoquinoline alkaloid biosynthesis. Characterization of the recombinant IpeOMT enzymes with integration of the enzymatic properties of the IpeGlu1 revealed that emetine biosynthesis branches off from N-deacetylisoipecoside through its 6-O-methylation by IpeOMT1, with a minor contribution by IpeOMT2, followed by deglucosylation by IpeGlu1. The 7-hydroxy group of the isoquinoline skeleton of the aglycon is methylated by IpeOMT3 prior to the formation of protoemetine that is condensed with a second dopamine molecule, followed by sequential O-methylations by IpeOMT2 and IpeOMT1 to form cephaeline and emetine, respectively. In addition to this central pathway of ipecac alkaloid biosynthesis, formation of all methyl derivatives of ipecac alkaloids in P. ipecacuanha could be explained by the enzymatic activities of IpeOMT1-IpeOMT3, indicating that they are sufficient for all O-methylation reactions of ipecac alkaloid biosynthesis.
Synthesis of Benzyltetrahydroisoquinoline Alkaloids with the Use of 1,3-Dithianes of Aromatic Aldehydes
Brozda, D.
, p. 2665 - 2670 (2007/10/02)
A practical synthesis of 1-benzyl-2-methyl-1,2,3,4-tetrahydroisoquinolines (4) is described. Condensation of 6,7-disubstituted N-methyl-3,4-dihydroisoquinolinium iodide 1 with 1,3-dithianes 2 gave addition products 3 from which alkaloids 4 were obtained by desulfuration. Key words: 1-benzyltetrahydroisoquinolines, dithianes, tetrahydroisoquinolinium alkaloids
