- 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
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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.
- Bartel, Karin,Bracher, Franz,Geisslinger, Franz,Keller, Marco,Sauvageot-Witzku, Karl,Schaefer, Michael,Urban, Nicole
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p. 2716 - 2725
(2022/01/12)
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- BIOMIMETIC OXIDATIONS OF BENZYLISOQUINOLINE ALKALOUDS. II. THE BIS(SALICYLALDEHYDE)ETHYLENEDIIMINECOBALT(II)-CATALYZED OXIDATION OF BENZYLISOQUINOLINES WITH OXYGEN
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The complex bis(salicylaldehyde)ethylenediiminecobalt(II) (CoII salen) catalyzes the oxidation of benzylisoquinoline alkaloids with oxygen.Aminium radicals are formed and give rise to 1,2-dehydrobenzylisoquinoline ions.Cleavage of the C(1)-C(9) bond via C(9) oxidation is observed in some instances.
- Canonica, Luigi,Galliani, Guido,Nali, Micaela,Rindone, Bruno,Tollari, Stefano
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- Alkaloid Formation through N-Oxide Intermediates; Regioselective Synthesis of (+/-)-Corytuberine by Redox Reaction
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Reaction of (+/-)-reticuline N-oxide (1) with cuprous chloride in methanol followed by treatment with sodium hydrosulphite gave the aporphine alkaloid, (+/-)-corytuberine (8) in good yield.Protoberberine alkaloids, (+/-)-coreximine (4) and (+/-)-scoulerin
- Kametani, Tetsuji,Ihara, Masataka
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p. 629 - 632
(2007/10/02)
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