l-N-Norarmepavine

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.

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“…The N-nor-alkaloids rac-norarmepavine (2b; from Nelumbo nucifer [41]) and rac-norcinnamolaurine (3b; from Cinnamomum sp. T.G.H.…”

Section: Resultsmentioning

confidence: 99%

“…13077 [ 36 ]), N -demethylphyllocryptine ( 3c; from Cryptocarya phyllosternon [ 37 – 38 ]) and thalifendlerine ( 4 ; from Thalictrum fendleri [ 39 – 40 ]) in yields ranging from 36 to 82%. The N -nor-alkaloids rac -norarmepavine ( 2b ; from Nelumbo nucifer [ 41 ]) and rac -norcinnamolaurine ( 3b ; from Cinnamomum sp. T.G.H.…”

Section: Resultsmentioning

confidence: 99%

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

Keller

Sauvageot-Witzku

Geisslinger

et al. 2021

Beilstein J. Org. Chem.

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Spaltung von DL‐Armepavin in optische Antipoden

Knabe

Horn

1967

Archiv der Pharmazie

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Die Basenphase war olig und enthielt nach dem DC hauptsiichlich Ausgangssubstanz (Rf 0,26) neben geringen Mengen von Lactam (Rf 0,88).Racem. Armepavin 1$Bt sich uber die diastereomeren (+)-Campher-10sulfonate in die optischen Antipoden spalten.DL-Armepavin sowie die optischen Antipoden D(-)-und L( +)-Armepavin sind in der Literatur vielfach beschrieben. DL-Armepavin wurde in Nelumbo luteal) und N. nucifera2) aufgefunden und auf verschiedenen Wegen synthetisch hergestellt3-6). D(-)-Armepavin wurde aus einigen Wildmohnarten isoliert : Papaver armeniacum7) P. floribundums), P. caucasicumg) sowie P. polychaetum, P. persicum und P. fugaxlo). Es wurde ferner durch Spaltung der Alkaloide Cycleaninll) 12) und N~r c y c l e a n i n l~) 0,0-Dimethyl-isochondrodendrin14), Dauricin15) und Pronucife-rinl6) mit Natrium in fliissigem Ammoniak gewonnen. *) Teilergebnis der Dissertation P . Horn, Braunschweig 1966.

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Modified synthesis of dl-N-norarmepavine and dl-armepavine

Sam

Bej

1967

Journal of Pharmaceutical Sciences

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l-N-Norarmepavine

Cited by 9 publications

References 10 publications

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

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

Spaltung von DL‐Armepavin in optische Antipoden

Modified synthesis of dl-N-norarmepavine and dl-armepavine

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