A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach

Nicolas D. Spiccia; James Burnley; Kamani Subasinghe; Christopher Perry; Laurent Lefort; W. Roy Jackson; Andrea J. Robinson

doi:10.1021/acs.joc.7b01257

A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach

Nicolas D. Spiccia, James Burnley, Kamani Subasinghe, Christopher Perry, Laurent Lefort, W. Roy Jackson, Andrea J. Robinson

School of Chemistry

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

3 Citations (Scopus)

Abstract

The development of an efficient, high yielding six-step convergent synthesis of the semisynthetic alkaloid (-)-perhydrohistrionicotoxin is described. The key transformations include the cross metathesis of a Brønsted-acid masked primary homoallylic amine with a vinyl cyclohexenone and a regioselective palladium catalyzed hydrogenation. This sequence generated the advanced Winterfeldt spirocyclic precursor in 47% overall yield, with a longest linear sequence of five steps.

Original language	English
Pages (from-to)	8725-8732
Number of pages	8
Journal	The Journal of Organic Chemistry
Volume	82
Issue number	16
DOIs	https://doi.org/10.1021/acs.joc.7b01257
Publication status	Published - 18 Aug 2017

Cite this

Spiccia, N. D., Burnley, J., Subasinghe, K., Perry, C., Lefort, L., Jackson, W. R., & Robinson, A. J. (2017). A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach. The Journal of Organic Chemistry, 82(16), 8725-8732. https://doi.org/10.1021/acs.joc.7b01257

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abstract = "The development of an efficient, high yielding six-step convergent synthesis of the semisynthetic alkaloid (-)-perhydrohistrionicotoxin is described. The key transformations include the cross metathesis of a Br{\o}nsted-acid masked primary homoallylic amine with a vinyl cyclohexenone and a regioselective palladium catalyzed hydrogenation. This sequence generated the advanced Winterfeldt spirocyclic precursor in 47% overall yield, with a longest linear sequence of five steps.",

author = "Spiccia, {Nicolas D.} and James Burnley and Kamani Subasinghe and Christopher Perry and Laurent Lefort and Jackson, {W. Roy} and Robinson, {Andrea J.}",

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doi = "10.1021/acs.joc.7b01257",

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A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach. / Spiccia, Nicolas D.; Burnley, James; Subasinghe, Kamani; Perry, Christopher; Lefort, Laurent; Jackson, W. Roy; Robinson, Andrea J.

In: The Journal of Organic Chemistry, Vol. 82, No. 16, 18.08.2017, p. 8725-8732.

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

TY - JOUR

T1 - A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach

AU - Spiccia, Nicolas D.

AU - Burnley, James

AU - Subasinghe, Kamani

AU - Perry, Christopher

AU - Lefort, Laurent

AU - Jackson, W. Roy

AU - Robinson, Andrea J.

PY - 2017/8/18

Y1 - 2017/8/18

N2 - The development of an efficient, high yielding six-step convergent synthesis of the semisynthetic alkaloid (-)-perhydrohistrionicotoxin is described. The key transformations include the cross metathesis of a Brønsted-acid masked primary homoallylic amine with a vinyl cyclohexenone and a regioselective palladium catalyzed hydrogenation. This sequence generated the advanced Winterfeldt spirocyclic precursor in 47% overall yield, with a longest linear sequence of five steps.

AB - The development of an efficient, high yielding six-step convergent synthesis of the semisynthetic alkaloid (-)-perhydrohistrionicotoxin is described. The key transformations include the cross metathesis of a Brønsted-acid masked primary homoallylic amine with a vinyl cyclohexenone and a regioselective palladium catalyzed hydrogenation. This sequence generated the advanced Winterfeldt spirocyclic precursor in 47% overall yield, with a longest linear sequence of five steps.

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U2 - 10.1021/acs.joc.7b01257

DO - 10.1021/acs.joc.7b01257

M3 - Article

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SP - 8725

EP - 8732

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

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A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach

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New metal catalysed tandem routes to nitrogen containing compounds