Epimeric 3-vinyl-4-piperdineacetic acids, synthetic precursors of cinchoma and indole alkaloids

Uskoković, Milan R.; Reese, C.; Lee, H. L.; Grethe, Guenter; Gutzwiller, J.

doi:10.1021/ja00751a059

Cited by 29 publications

(13 citation statements)

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“…3 u100 ml in ethanovether), and stirring was continued for 1 h. This was followed by addition of several drops of glacial acetic acid and by evaporation to dryness. It gave 3.37 g of crude product, which was chromatographed on preparative silica gel plates with ethyl Racemic trans-I -benzoyl-3-(2-hydroxyethyl)-4-piperidineacetic acid methyl ester (1 1) from racemic trans-2-benzoyl-decahydro-6-isoquinolone (9). To a solution of 5.0 g (19.4 mmol) of 9 in 80 ml of CHzC12 was added 6.67 g (33 mmol) of 85% m-chloroperbenzoic acid and 10 g of NaHC03.…”

Section: Experimental Partmentioning

confidence: 99%

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Total synthesis of racemic ajmalicine and 19‐epi‐ajmalicine

Gutzwiller

Pizzolato

Uskoković

1981

Helvetica Chimica Acta

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Summaryrac.-Ajmalicine (31) and 19-epi-ajmalicine (30) have been synthesized by a convergent route from the preformed D, E-ring moieties 25 and 27 and tryptophyl bromide. Two syntheses of the trans-1 -benzoyl-3-vinyl-4-piperidineacetic acid (13), used in the preparation of 25 and 27, are also described.The alkaloids of heteroyohimbine family with normal configuration [ 11 are known to exhibit cardiovascular activities, and therefore, they have been subject of a continuous investigation by isolation from natural sources and synthesis. Ajmalicine . Optically active ajmalicine has been synthesized from naturally occurring elenolic acid [7]. In this report we describe the synthesis of' racemic ajmalicine (31) and 19-epiajmalicine (30) by assembling their molecules from the fully preformed D, E-ring moieties and tryptophyl bromide [8]. This synthetic approach is convenient for the preparation of differently substituted derivatives by using the appropriate tryptophyl bromides. The C ( 19) epimeric trans-D, E-ring moieties 25 and 27 were synthesized from the trans-l-benzoyl-3-vinyl-4-piperidine-acetic acid methyl esterThe ester 14 was obtained by two different methods, both leading to the intermediate chlorinated ester 8 (Scheme 1). In the first case [9], we started from the known trans-piperidoneacetic acid ester 1 [ 101, which was transformed in high yield to piperidineacetic acid ester 3. This was accomplished by 0-alkylation with triethyloxonium fluoroborate and reduction of the imino ether 2 with sodium borohydride. The functionalization of the ethyl side chain was effected by LofJerFreitag rearrangement: Chlorination of 3 or 4 with N-chlorosuccinimide (NCS) in ether gave in high yields the chloroamines 5 or 6, which on irradiation in trifluoro-(14). l )2,

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Section: Experimental Partmentioning

confidence: 99%

“…Besides 8, the dechlorinated product 18 and two dehydro-products 19 and 20 were also isolated (Scheme2). A mechanism for the formation of these by-products has been previously proposed [9]. As a second source of the chlorinated ester 8, we have used the trans-Nbenzoylisoquinolone 9 [ 1 11.…”

mentioning

confidence: 99%

Total synthesis of racemic ajmalicine and 19‐epi‐ajmalicine

Gutzwiller

Pizzolato

Uskoković

1981

Helvetica Chimica Acta

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“…When three quivalents of Et2AlCl were employed (-78 °C, 3 h), cleavage of the benzyl ester group resulted. We turned our attention to the synthesis of diene 13 by a route similar to that used in the preparation of 5, reasoning that the methyl ester and N-benzoyl protective groups would be more stable to the projected cyclization conditions and, in the event of the successful ene cyclization, would provide known diastereomeric piperidines 14a and 14b 21 (Scheme 2). To circumvent the apparent intramolecular condensation reaction observed in the alkylation of 10, we examined the alkylation of the dianion of acid amide 15.…”

Section: Resultsmentioning

confidence: 99%

Synthetic studies towards N-substituted 3-vinyl-4-piperidineacetic acid derivatives

Johnson¹,

Gribble²

2019

Arkivoc

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The synthesis and full characterization of two new (E)-2-butenyl)-5-amino-2-pentenoates, (Z)-4-[N-(3-buten-1-yl)benzamido]-2-buten-1-ol, and (Z)-1-chloro-4-[N-(3-buten-l-yl)benzamido]-2-butene are reported. These were designed as substrates for a projected thermal ene cyclization leading to the N-substituted 3-vinyl-4piperidineacetic acid scaffold. Although conditions for this ene-cyclization have not yet been uncovered, the ease of preparation of these ene-cyclization substrates gives promise for their future use.

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“…Die erste Synthese von N ‐Benzoylmerochinen ( 41 a ) durch Uskokovic et al erinnert ein wenig an die von Woodward (Schema ) bei seiner Herstellung von Homomerochinen ( 17 ) 160i,j. Zunächst wurde N ‐Benzoylhexahydroisochinolon ( 53 ) katalytisch hydriert und eine cis/trans ‐Mischung des Octahydroderivats erhalten, in der das gewünschte cis ‐Diastereomer 53 a überwog 161.…”

Section: Meisterung Der C8‐n‐strategie: Die Erste Totalsynthese Vounclassified

Die Jagd auf Chinin: Etappenerfolge und Gesamtsiege

Kaufman

Rúveda

2005

Angewandte Chemie

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Die Synthese von Chinin war lange Zeit ein schwer erreichbares Ziel. Im Jahr 2004, in das der 60. Jahrestag der Veröffentlichung von Woodward und Doering über Chinin fiel, gelangen zwei neuartige, stereokontrollierte Totalsynthesen dieses Naturstoffs. Zusammen mit der ersten stereokontrollierten Totalsynthese von Chinin durch Stork 2001 belegen sie das auflebende Interesse von Organikern an der Synthese dieser Verbindung, die einst ein Wundermittel war. Diese aktuellen Veröffentlichungen über Chinin demonstrieren eindrucksvoll den immensen Fortschritt organischer Synthesemethoden während der letzten drei Jahrzehnte seit den partiell kontrollierten Chininsynthesen durch Uskokovic. Nach einem Abriss der historischen Bedeutung von Chinin als Antimalaria‐Wirkstoff und einer kurzen Schilderung der Experimente, die zu seiner Isolierung und der Aufklärung seiner Struktur beitrugen, berichten wir über die ersten Verfahren zum Aufbau und schließlich die Totalsynthesen dieses Naturstoffs.

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Epimeric 3-vinyl-4-piperdineacetic acids, synthetic precursors of cinchoma and indole alkaloids

Cited by 29 publications

References 0 publications

Total synthesis of racemic ajmalicine and 19‐epi‐ajmalicine

Total synthesis of racemic ajmalicine and 19‐epi‐ajmalicine

Synthetic studies towards N-substituted 3-vinyl-4-piperidineacetic acid derivatives

Die Jagd auf Chinin: Etappenerfolge und Gesamtsiege

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