Enantioselective Total Synthesis of (+)‐Jungermatrobrunin A

Wu, Ji‐Wei; Kadonaga, Yuichiro; Hong, Bo; Wang, Jin; Lei, Xiaoguang

doi:10.1002/anie.201903682

Cited by 44 publications

(18 citation statements)

References 61 publications

(24 reference statements)

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“…Isodon diterpenoids, a large family of terpenoid natural products, , are biosynthetically derived from geranylgeranyl-diphosphate (GGPP) via series terpenoid cyclase-catalyzed carbocationic rearrangements. , According to the initial biosynthetic hypothesis, jungermannenone diterpenoids ( 86 ) are derived from ent -kaurane diterpenoids ( 85 ) via two possible carbocationic rearrangement pathways (Scheme A). , During the synthesis of complex Isodon diterpenoids by Lei and co-workers, , initial attempts to convert ent -kaurane-type skeletons into jungermannenone-type skeletons via carbocationic rearrangement on a model substrate were unsuccessful. Interconversion between ent -kauranes and jungermannenones was ultimately achieved via late-stage photochemical rearrangement of the bicyclo[3.2.1]octene moiety (Scheme B).…”

Section: Biosynthetic Implicationsmentioning

confidence: 99%

Late-Stage Diversification of Natural Products

2020

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Late-stage diversification of natural products is an efficient way to generate natural product derivatives for drug discovery and chemical biology. Benefiting from the development of site-selective synthetic methodologies, late-stage diversification of natural products has achieved notable success. This outlook will outline selected examples of novel methodologies for site-selective transformations of reactive functional groups and inert C–H bonds that enable late-stage diversification of complex natural products. Accordingly, late-stage diversification provides an opportunity to rapidly access various derivatives for modifying lead compounds, identifying cellular targets, probing protein–protein interactions, and elucidating natural product biosynthetic relationships.

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Section: Biosynthetic Implicationsmentioning

confidence: 99%

Late-Stage Diversification of Natural Products

2020

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“…The copper-catalyzed asymmetric conjugate addition (ACA) of organometallic species is a powerful tool to synthesize new C–C bonds from α,β-unsaturated carbonyl compounds. − After tremendous attention for more than 20 years, the ACA is now arguably one of the most useful asymmetric transformations available to synthetic chemists, and has been used in the synthesis of a variety of natural products. − However, there are still a number of challenges that need to be met to reach its full potential. A lack of robustness in Cu-catalyzed ACAs is well-known, and widely implicated in preventing the approach from enriching mainstream synthetic strategies and methods, , though it should be mentioned that examples of ACAs to give >50 g of product have recently been reported. , Another reason for the underutilization of this method stems from method development being carried out with commonly available substrates, so that seemingly obvious extensions to slightly unusual or more highly decorated reaction partners do not display the desired reactivity patterns. , …”

Section: Introductionmentioning

confidence: 99%

Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach

2019

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The development of catalytic enantioselective methods is routinely carried out using easily accessible and prototypical substrates. This approach to reaction development often yields asymmetric methods that perform poorly using substrates that are sterically or electronically dissimilar to those used during the reaction optimization campaign. Consequently, expanding the scope of previously optimized catalytic asymmetric reactions to include more challenging substrates is decidedly nontrivial. Here, we address this challenge through the development of a systematic workflow to broaden the applicability and reliability of asymmetric conjugate additions to substrates conventionally regarded as sterically and electronically demanding. The copper-catalyzed asymmetric conjugate addition of alkylzirconium nucleophiles to form tertiary centers, although successful for linear alkyl chains, fails for more sterically demanding linear α,β-unsaturated ketones. Key to adapting this method to obtain high enantioselectivity was the synthesis of modified phosphoramidite ligands, designed using quantitative structure–selectivity relationships (QSSRs). Iterative rounds of model construction and ligand synthesis were executed in parallel to evaluate the performance of 20 chiral ligands. The copper-catalyzed asymmetric addition is now more broadly applicable, even tolerating linear enones bearing tert-butyl β-substituents. The presence of common functional groups is tolerated in both nucleophiles and electrophiles, giving up to 99% yield and 95% ee across 20 examples.

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“…Next, upon treatment with Sc(OTf) 3 /Ac 2 O, simultaneous exchange of both TMS ether and MOM ether with acetyl ester occurred smoothly to generate triacetate 56 , of which in‐situ α‐methylenation and selected acetate cleavage at the C12 position (under basic conditions) delivered (−)‐ 57 in 67% yield. [ 16 ]…”

Section: Function‐oriented Synthesis For Target Identification and Momentioning

confidence: 99%

Function‐Oriented Natural Product Synthesis

Chen

Lei

2021

Chin. J. Chem.

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What is the most favorite and original chemistry developed in your research group? By far the most original and groundbreaking work we have done is the discovery of the first naturally occurring TRUE Diels-Alderase which shows tremendous synthetic potential in biocatalysis for efficiently making structurally complex and bioactive molecules. How do you get into this specific field? Could you please share some experiences with our readers? I have a great passion in synthetic chemistry, and I am always fascinated by making organic molecules that may help us explore new biology and develop medicine for human diseases. Therefore, my research programs are relatively broad, spanning from natural product synthesis, chemical biology, synthetic biology, biocatalysis to drug discovery. What is the most important personality for scientific research? In my personal opinion, curiosity, ambition, and dedication are the most important personalities for scientific research. What is your favorite journal(s)? My favorite journals are: 1) Cell, when you read a Cell paper, you can get a full story of the original discovery and understand the detailed logic on how the research is planned and conducted; 2) Accounts of Chemical Research, this journal provides a short review on how a chemist establishes a specific new research field, very inspiring! What's your hobbies? I love many sports, soccer, American football, basketball, etc. I am also good at Seal Cutting, one of the four major traditional Chinese arts. If you have anything else to tell our readers, please feel free to do so. I would like to share one advice with the young scientists who just start their independent research career: BE DIFFERENT from your Ph.D. and Postdoc advisors, try to establish your own research direction! It's always easy to quickly get paper published when you take advantage of your advisor's research system, but it's very challenging to establish your own reputation and prove your originality in this way.

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Enantioselective Total Synthesis of (+)‐Jungermatrobrunin A

Cited by 44 publications

References 61 publications

Late-Stage Diversification of Natural Products

Late-Stage Diversification of Natural Products

Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach

Function‐Oriented Natural Product Synthesis

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