Synthesis of Calystegine A(3) from Glucose by the Use of Ring-Closing Metathesis

Rune Nygaard Monrad, Charlotte Bressen Pipper, Robert Madsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

A synthesis of the nortropane alkaloid calystegine A(3) is described from D-glucose. The key step employs a zinc-mediated tandem reaction where a benzyl-protected methyl 6-iodo glucoside is fragmented to give an unsaturated aldehyde, which is then transformed into the corresponding benzylimine and allylated in the same pot. The functionalized nona-1,8-diene, thus obtained, is converted into the seven-membered carbon skeleton in calystegine A(3) by ring-closing olefin metathesis. Subsequent deoxygenation by the Barton-McCombie protocol, hydroboration and oxidative workup followed by hydrogenolysis affords calystegine A(3). The synthesis uses a total of 13 steps from glucose and confirms the absolute configuration of the natural product.
Original languageEnglish
JournalEuropean Journal of Organic Chemistry
Issue number20
Pages (from-to)3387-3395
ISSN1434-193X
DOIs
Publication statusPublished - 2009

Keywords

  • Natural products
  • Total synthesis
  • Metathesis
  • Carbohydrates
  • Allylation

Cite this

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title = "Synthesis of Calystegine A(3) from Glucose by the Use of Ring-Closing Metathesis",
abstract = "A synthesis of the nortropane alkaloid calystegine A(3) is described from D-glucose. The key step employs a zinc-mediated tandem reaction where a benzyl-protected methyl 6-iodo glucoside is fragmented to give an unsaturated aldehyde, which is then transformed into the corresponding benzylimine and allylated in the same pot. The functionalized nona-1,8-diene, thus obtained, is converted into the seven-membered carbon skeleton in calystegine A(3) by ring-closing olefin metathesis. Subsequent deoxygenation by the Barton-McCombie protocol, hydroboration and oxidative workup followed by hydrogenolysis affords calystegine A(3). The synthesis uses a total of 13 steps from glucose and confirms the absolute configuration of the natural product.",
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author = "Monrad, {Rune Nygaard} and Pipper, {Charlotte Bressen} and Robert Madsen",
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journal = "European Journal of Organic Chemistry",
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Synthesis of Calystegine A(3) from Glucose by the Use of Ring-Closing Metathesis. / Monrad, Rune Nygaard; Pipper, Charlotte Bressen; Madsen, Robert.

In: European Journal of Organic Chemistry, No. 20, 2009, p. 3387-3395.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Synthesis of Calystegine A(3) from Glucose by the Use of Ring-Closing Metathesis

AU - Monrad, Rune Nygaard

AU - Pipper, Charlotte Bressen

AU - Madsen, Robert

PY - 2009

Y1 - 2009

N2 - A synthesis of the nortropane alkaloid calystegine A(3) is described from D-glucose. The key step employs a zinc-mediated tandem reaction where a benzyl-protected methyl 6-iodo glucoside is fragmented to give an unsaturated aldehyde, which is then transformed into the corresponding benzylimine and allylated in the same pot. The functionalized nona-1,8-diene, thus obtained, is converted into the seven-membered carbon skeleton in calystegine A(3) by ring-closing olefin metathesis. Subsequent deoxygenation by the Barton-McCombie protocol, hydroboration and oxidative workup followed by hydrogenolysis affords calystegine A(3). The synthesis uses a total of 13 steps from glucose and confirms the absolute configuration of the natural product.

AB - A synthesis of the nortropane alkaloid calystegine A(3) is described from D-glucose. The key step employs a zinc-mediated tandem reaction where a benzyl-protected methyl 6-iodo glucoside is fragmented to give an unsaturated aldehyde, which is then transformed into the corresponding benzylimine and allylated in the same pot. The functionalized nona-1,8-diene, thus obtained, is converted into the seven-membered carbon skeleton in calystegine A(3) by ring-closing olefin metathesis. Subsequent deoxygenation by the Barton-McCombie protocol, hydroboration and oxidative workup followed by hydrogenolysis affords calystegine A(3). The synthesis uses a total of 13 steps from glucose and confirms the absolute configuration of the natural product.

KW - Natural products

KW - Total synthesis

KW - Metathesis

KW - Carbohydrates

KW - Allylation

U2 - 10.1002/ejoc.200900310

DO - 10.1002/ejoc.200900310

M3 - Journal article

SP - 3387

EP - 3395

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

SN - 1434-193X

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