Total Synthesis and Biological Evaluation of (−)‐Englerin A and B: Synthesis of Analogues with Improved Activity Profile

Radtke, Lea; Willot, Matthieu; Sun, Hongyan; Ziegler, Slava; Sauerland, Stephanie; Strohmann, Carsten; Fröhlich, Roland; Habenberger, Peter; Waldmann, Herbert; Christmann, Mathias

doi:10.1002/anie.201007790

Cited by 82 publications

(83 citation statements)

References 19 publications

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“…Christmann and co-workers recorded the first synthesis and confirmed the absolute configuration of ent -(+)-englerin A in 2009. These authors published a follow-up synthesis of the natural enantiomer along with several analogs in 2011 [10,11]. Bicycle 2 is synthesized in 11 steps from (−)-nepetalactone and can be engaged in a transannular epoxide opening to generate the bridging ether with high regioselectivity.…”

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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“…Christmann’s group, for example, observed a rapid loss of activity when the 7-iPr group was reduced to ethyl ( 37 , IC 50 950 nM) and then methyl ( 38 , 4.6 μ M). 23 …”

Section: Englerin Analoguesmentioning

confidence: 99%

“…22 The (+)-enantiomer was later found to be inactive at 1 μ M in A498 cells, while the IC 50 of the synthetic (−)-enantiomer was 45 nM. 23 Synthesis of the natural (−)-enantiomer of englerin A, which required synthesis of the unnatural (−)-nepetalactone, was reported by the same group in 2011. 23 …”

Section: Introductionmentioning

confidence: 99%

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Englerins: A Comprehensive Review

Zhao

Fash

et al. 2017

J. Nat. Prod.

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Graphical Abstract In the decade since the discovery of englerin A (1) and its potent activity in cancer models, this natural product and its analogues have been the subject of numerous chemical, biological, and preclinical studies by many research groups. This review summarizes published findings and proposes further research directions required for entry of an englerin analogue into clinical trials for kidney cancer and other conditions.

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“…This important achievement established the absolute stereochemistry of the natural product, and the Christmann group later described a second-generation synthesis of the naturally occurring enantiomer of englerin A in which a number of transformations were improved. 6 This work also provided an informative structure-function study that identified three C6-acyl analogues with greater potency against renal cancer cell lines than that of the natural product.…”

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confidence: 97%

Synthetic Strategies toward the Guaiane Sesquiterpene Englerin A

Chain¹

2011

Synlett

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Englerin A is a guaiane sesquiterpene with potent and selective growth inhibition activity against six human renal cancer cell lines. Since the disclosure of its structure in 2009, englerin A has been the subject of intense study by the synthetic organic chemistry community, and several elegant strategies have been developed for the total synthesis of this exciting natural product. These strategies are discussed herein.

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Total Synthesis and Biological Evaluation of (−)‐Englerin A and B: Synthesis of Analogues with Improved Activity Profile

Cited by 82 publications

References 19 publications

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

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

Englerins: A Comprehensive Review

Synthetic Strategies toward the Guaiane Sesquiterpene Englerin A

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