Structure of parthenolide

Govindachari, T. R.; Joshi, B. S.; Kamat, V. N.

doi:10.1016/s0040-4020(01)98314-0

Cited by 81 publications

(38 citation statements)

References 16 publications

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“…anticancer, antimalarial, antiviral, antibacterial, antifungal, anti-inflammatory). [1,2] Of particular significance are natural products such as helenalin (1), [3] the anti-inflammatory active ingredient of Arnica, which is widely used in liniments and ointments for the treatment of strains, sprains, and bruises; [4] parthenolide (2), [5] a sesquiterpene lactone isolated from the medicinal herb feverfew, which possesses interesting anti-inflammatory, anticancer and antiviral properties; [6] the hispitolides (e.g. hispitolide A, 3), a newly discovered family of compounds exhibiting activity against the hepatitis C virus (HCV); [7] and arglabin (4), [8] a tumor inhibitor that was the subject of an elegant total synthesis in 2007.…”

Section: Introductionmentioning

confidence: 99%

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

Kitson¹,

Millemaggi²,

Taylor³

2009

Angew Chem Int Ed

401

249

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The amount of research activity concerning alpha-methylene-gamma-butyrolactones and alpha-alkylidene-gamma-butyrolactones has increased dramatically in recent years. This Review summarizes the structural types, biological activities, and biosynthesis of these compounds, concentrating on publications from the past 10 years. Traditional approaches to alpha-methylene-gamma-butyrolactones and alpha-alkylidene-gamma-butyrolactones are then reviewed together with novel approaches, including those from our own research group, reported more recently.

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Section: Introductionmentioning

confidence: 99%

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

Kitson¹,

Millemaggi²,

Taylor³

2009

Angew Chem Int Ed

401

249

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“…α-Bromination of lactone 7 with LDA and CBr 4 , followed by dehydrobromination with TBAF, [13] gave rise to 7-epi-parthenolide (−)-8 (60% over 2 steps), an unnatural epimer of the biologically active [14] sesquiterpene lactone parthenolide. [15] While parthenolide has been successfully isolated in quantity recently, [16] none of its epimers have been synthesized to date, and thus the biological activity of 8 has not yet been explored. (−)-4-Hydroxyallohedycaryol (12) was obtained in a four-step sequence from (+)-1 by: 1) directed epoxidation with VO(acac) 2 to give bis-epoxide 9 (77% yield); 2) chemoselective reduction of the less-hindered epoxide to diol (+)-10 with LiAlH 4 ; 3) mesylation of the 2° alcohol providing (+)-11 (44% over 2 steps); and 4) reductive elimination of the epoxy mesylate (+)-11 with lithium naphthalenide to afford (−)-12 in 65% yield, together with recovered diol 10 in 23% yield.…”

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confidence: 99%

Scalable, Enantioselective Synthesis of Germacrenes and Related Sesquiterpenes Inspired by Terpene Cyclase Phase Logic

et al. 2012

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Our laboratory has a longstanding interest in harvesting new chemical knowledge by learning from terpene biosynthesis. The straightforward construction of carbocyclic terpene backbones such as epoxy-germacrenol (1, Scheme 1A) in a low oxidation state (cyclase phase) followed by regio-, chemo-, and stereoselective oxidative modifications (oxidase phase) allow Nature to access a wide variety of related family members in a divergent manner. [1] Earlier this year, we reported our initial forays into the redox-economic synthesis of terpenes that resemble 1 by oligomerization of unfunctionalized isoprene (Scheme 1B, path a). [2] These studies ultimately led us to a new approach that utilizes the more advanced, yet readily available, C 15 building block farnesol (2, Scheme 1A) as a starting point. In this communication, a short, efficient, scalable, and enantioselective synthesis of 1 is described. Furthermore, we demonstrate how the key intermediate 1 can be processed not only to germacrane-type natural products by chemo-and stereoselective oxidations, but also to a variety of polycyclic sesquiterpene frameworks (like selinanes, guaianes, or elemenes) by acid-mediated transannular cyclization reactions.For the goal of establishing a scalable, divergent, and broadly applicable entry to a variety of related sesquiterpene families, the germacrenes were identified as strategic key intermediates due to the following reasons: 1) germacrenes constitute a large class of cyclic terpenes, many of which have been shown to exhibit promising bioactivities and, in addition, are of growing importance in the perfumery industry; 2) germacrenes are known to be a biosynthetic linchpin en route to various related terpene congeners; and 3) most importantly, many studies have demonstrated that germacrenes can be transformed into mono-, di-, and tricyclic sesquiterpene subclasses (e.g., the elemenes, cadinanes, eudesmanes, guaianes, and bourbonanes) with the "Achilles heel" of these approaches being the accessibility of germacrene precursors in quantity. [3] Despite the industrial interest in terpene natural products, most of the naturally occurring germacrenes and their congeners are not easily available in bulk quantities due to a variety of challenges associated with their synthesis and/or isolation: germacrenes featuring a * pbaran@scripps.edu. † These authors contributed equally to the paper.Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Although the total synthesis of sesquiterpenes has been an area of intense research efforts for decades, [4] there is still no reliable synthetic pathway to rapidly forge the ten-membered germacrene carbocycle. The most effective synthetic approaches published to date (Scheme 1B) suffer from serious drawbacks such as low overall yield, poor step economy, and/or are impractical to perform on scale In addition, these syntheses either yield racemic products or start from chiral-pool starting materials. Whereas Nature's cyclase enzymes c...

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“…28,29) Among sesquiterpene lactones, parthenolide and michampanolide 33,34) Isoquinoline alkaloids form a large group of natural leishmanicidal compounds. Although liriodenine or its analogues have not yet been isolated from M. champaca heartwood, it would be reasonable to assume that leishmanicidal activity in heartwood is due to such compounds.…”

Section: Michelia Champaca Linn (Local Name Sagawa)mentioning

confidence: 99%