Use of the kinetically controlled Pictet-Spengler reaction in the asymmetric synthesis of indole alkaloids

Formal syntheses of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline

Patrick D. Bailey, Neil R. McLay

Research output: Contribution to journalArticle

Abstract

By employing the kinetically controlled Pictet-Spengler reaction L-tryptophan was used as the chiral starting material for the synthesis of the cis-1,3-disubstituted tetrahydro-ß-carboline 14a. Protection of the two nitrogens and subsequent cyclisation/decarboxylation led to generation of the bridged ketone (-)-(7c), which was shown to be optically pure within our detection limits (ee >95%). Simple protecting group modifications gave access to (-)-7a and (-)-7b, and constituted formal synthesis of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline. These results demonstrate that such alkaloids with the correct absolute configuration are accessible in a stereocontrolled manner from L-tryptophan.

Original languageEnglish
Pages (from-to)441-449
Number of pages9
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number4
Publication statusPublished - 1993

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Ajmaline
Indole Alkaloids
Tryptophan
Carbolines
Cyclization
Ketones
Alkaloids
Nitrogen
koumine

Cite this

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title = "Use of the kinetically controlled Pictet-Spengler reaction in the asymmetric synthesis of indole alkaloids: Formal syntheses of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline",
abstract = "By employing the kinetically controlled Pictet-Spengler reaction L-tryptophan was used as the chiral starting material for the synthesis of the cis-1,3-disubstituted tetrahydro-{\ss}-carboline 14a. Protection of the two nitrogens and subsequent cyclisation/decarboxylation led to generation of the bridged ketone (-)-(7c), which was shown to be optically pure within our detection limits (ee >95{\%}). Simple protecting group modifications gave access to (-)-7a and (-)-7b, and constituted formal synthesis of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline. These results demonstrate that such alkaloids with the correct absolute configuration are accessible in a stereocontrolled manner from L-tryptophan.",
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year = "1993",
language = "English",
pages = "441--449",
journal = "Journal of the Chemical Society, Perkin Transactions 1",
issn = "1472-7781",
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T1 - Use of the kinetically controlled Pictet-Spengler reaction in the asymmetric synthesis of indole alkaloids

T2 - Formal syntheses of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline

AU - Bailey, Patrick D.

AU - McLay, Neil R.

PY - 1993

Y1 - 1993

N2 - By employing the kinetically controlled Pictet-Spengler reaction L-tryptophan was used as the chiral starting material for the synthesis of the cis-1,3-disubstituted tetrahydro-ß-carboline 14a. Protection of the two nitrogens and subsequent cyclisation/decarboxylation led to generation of the bridged ketone (-)-(7c), which was shown to be optically pure within our detection limits (ee >95%). Simple protecting group modifications gave access to (-)-7a and (-)-7b, and constituted formal synthesis of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline. These results demonstrate that such alkaloids with the correct absolute configuration are accessible in a stereocontrolled manner from L-tryptophan.

AB - By employing the kinetically controlled Pictet-Spengler reaction L-tryptophan was used as the chiral starting material for the synthesis of the cis-1,3-disubstituted tetrahydro-ß-carboline 14a. Protection of the two nitrogens and subsequent cyclisation/decarboxylation led to generation of the bridged ketone (-)-(7c), which was shown to be optically pure within our detection limits (ee >95%). Simple protecting group modifications gave access to (-)-7a and (-)-7b, and constituted formal synthesis of (-)-ajmaline, (-)-koumine, (-)-taberpsychine, (-)-koumidine and (-)-suavoline. These results demonstrate that such alkaloids with the correct absolute configuration are accessible in a stereocontrolled manner from L-tryptophan.

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JO - Journal of the Chemical Society, Perkin Transactions 1

JF - Journal of the Chemical Society, Perkin Transactions 1

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