A Brief Synthesis of (−)-Englerin A

Li, Zhenwu; Nakashige, Mika L.; Chain, William J.

doi:10.1021/ja201921j

Cited by 114 publications

(82 citation statements)

References 36 publications

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“…But perhaps the most elegant and efficient synthesis to date was accomplished by Chain and co-workers in 2011 [15]. Using simple carbonyl chemistry, these authors synthesize englerin A in only eight linear steps.…”

Section: Stereochemistry-based Strategies: the Power Of Substrate Relaymentioning

confidence: 99%

Synthesis of Medicinally Relevant Terpenes: Reducing the Cost and Time of Drug Discovery

Jansen

Shenvi

2014

Future Med. Chem.

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Terpenoids constitute a significant fraction of molecules produced by living organisms that have found use in medicine and other industries. Problems associated with their procurement and adaptation for human use can be solved using chemical synthesis, which is an increasingly economical option in the modern era of chemistry. This article documents, by way of individual case studies, strategies for reducing the time and cost of terpene synthesis for drug discovery. A major trend evident in recent syntheses is that complex terpenes are increasingly realistic starting points for both medicinal chemistry campaigns and large-scale syntheses, at least in the context of the academic laboratory, and this trend will likely penetrate the commercial sector in the near future.

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Section: Stereochemistry-based Strategies: the Power Of Substrate Relaymentioning

confidence: 99%

Synthesis of Medicinally Relevant Terpenes: Reducing the Cost and Time of Drug Discovery

Jansen

Shenvi

2014

Future Med. Chem.

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“…3 Several total synthesis of englerin A 4,5,6,7,8,9,10,11,12,13,14,15,16,17 and analogues 18,19,20,21,22,23,24,25 have been reported to date. Recently, two distinct mechanisms for englerin A’s anticancer activity have been proposed, agonism of PKCθ 26 and agonism of TRPC4/5.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New (−)‐Englerin Analogues

et al. 2016

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We report the synthesis and biological evaluation of a series of (−)‐englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier‐to‐synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth‐inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).

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“…[3,4] In all cases, the use of SmI 2 enabled strategic bond constructions for the rapid generation of the challenging target frameworks. The recent syntheses of strychnine [5] and englerin A [6] using SmI 2 -mediated cyclizations provide a vivid illustration of the power of the reagent for the total synthesis of complex and important targets.…”

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confidence: 99%

“…The impressive synthesis of englerin A, recently disclosed by Chain and co-workers, [6] relies on an imaginative sequence climaxing in a SmI 2 -mediated cyclization to form the tricyclic core and establishing five stereocenters (Scheme 5). The enantioselective total synthesis of englerin A was completed in only 8 steps and 20 % overall yield.…”

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confidence: 99%