Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A

Thomas O. Ronson; Michael J. Burns; Martin H H Voelkel; Kieren J. Evans; Jason M. Lynam; Richard J K Taylor; Ian J S Fairlamb

doi:10.1002/chem.201504089

Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A

Thomas O. Ronson, Michael J. Burns, Martin H H Voelkel, Kieren J. Evans, Jason M. Lynam, Richard J K Taylor^*, Ian J S Fairlamb

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including Au^I-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products.

Original language	English
Pages (from-to)	18905-18909
Number of pages	5
Journal	Chemistry : A European Journal
Volume	21
Issue number	52
DOIs	https://doi.org/10.1002/chem.201504089
Publication status	Published - 21 Dec 2015

Keywords

dienes
macrocycles
natural products
palladium
total synthesis

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10.1002/chem.201504089

Cite this

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title = "Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A",

abstract = "The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including AuI-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products.",

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author = "Ronson, {Thomas O.} and Burns, {Michael J.} and Voelkel, {Martin H H} and Evans, {Kieren J.} and Lynam, {Jason M.} and Taylor, {Richard J K} and Fairlamb, {Ian J S}",

year = "2015",

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doi = "10.1002/chem.201504089",

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AU - Ronson, Thomas O.

AU - Burns, Michael J.

AU - Voelkel, Martin H H

AU - Evans, Kieren J.

AU - Lynam, Jason M.

AU - Taylor, Richard J K

AU - Fairlamb, Ian J S

PY - 2015/12/21

Y1 - 2015/12/21

N2 - The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including AuI-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products.

AB - The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including AuI-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products.

KW - dienes

KW - macrocycles

KW - natural products

KW - palladium

KW - total synthesis

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DO - 10.1002/chem.201504089

M3 - Article

AN - SCOPUS:84954547948

SN - 0947-6539

VL - 21

SP - 18905

EP - 18909

JO - Chemistry : A European Journal

JF - Chemistry : A European Journal

IS - 52

ER -

Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A

Abstract

Keywords

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IAN JAMES STEWART FAIRLAMB

JASON MARTIN LYNAM

RICHARD JOHN KENNETH TAYLOR