Enantioselective synthesis of an ophiobolin sesterterpene via a programmed radical cascade.
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TLDR
A disparate synthetic approach to complex terpenes whereby simple prenyl-derived chains are cyclized using radical, rather than cationic, reaction pathways, which lays the foundation for efficient synthesis of terpenoid ring systems of interest in medicinal research, particularly those that have been historically challenging to access.Abstract:
Cyclase enzymes weave simple polyprenyl chains into the elaborate polycyclic ring systems of terpenes, a sequence that is often difficult to emulate under abiotic conditions. Here we report a disparate synthetic approach to complex terpenes whereby simple prenyl-derived chains are cyclized using radical, rather than cationic, reaction pathways. This strategy allowed us to efficiently forge the intricate 5-8-5 fused ring systems found in numerous complex natural product classes and also enabled a nine-step total synthesis of (–)-6- epi- ophiobolin N, a member of the large family of cytotoxic ophiobolin sesterterpenes. A small-molecule thiol catalyst was found to override the inherent diastereoselectivity observed during a reductive radical cascade cyclization process. This work lays the foundation for efficient synthesis of terpenoid ring systems of interest in medicinal research, particularly those that have been historically challenging to access.read more
Citations
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Radicals: Reactive Intermediates with Translational Potential
TL;DR: This Perspective illustrates the defining characteristics of free radical chemistry, beginning with its rich and storied history, and studies from the laboratory are discussed along with recent developments emanating from others in this burgeoning area.
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Structural and Chemical Biology of Terpenoid Cyclases.
TL;DR: Key advances in terpenoid cyclase structural and chemical biology are reviewed, focusing mainly on ter penoid cyclases and related prenyltransferases for which X-ray crystal structures have informed and advanced the authors' understanding of enzyme structure and function.
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Cyclopropanation Strategies in Recent Total Syntheses
TL;DR: An overview of the most important and widely used cyclopropanation techniques is presented, followed by a discussion of elegant approaches and clever solutions that have been developed to enable the synthesis of various uniquecyclopropane natural products or use of cycloprostanes as versatile strategic intermediates.
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Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products
TL;DR: This review highlights 21st century terpene total syntheses which themselves use small, ter pene-derived materials as building blocks and an outlook to the future of research in this area is highlighted.
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Photoexcitation of flavoenzymes enables a stereoselective radical cyclization
Kyle F. Biegasiewicz,Simon J. Cooper,Xin Gao,Daniel G. Oblinsky,Ji Hye Kim,Samuel E. Garfinkle,Leo A. Joyce,Braddock A. Sandoval,Gregory D. Scholes,Todd K. Hyster +9 more
TL;DR: It is found that photoexcitation of flavin-dependent “ene”-reductases changes their catalytic function, enabling these enzymes to promote an asymmetric radical cyclization, furnished a previously unknown biocatalytic reaction.
References
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Dimethyloxosulfonium Methylide ((CH3)2SOCH2) and Dimethylsulfonium Methylide ((CH3)2SCH2). Formation and Application to Organic Synthesis
E. J. Corey,Michael Chaykovsky +1 more
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Polarity-reversal catalysis of hydrogen-atom abstraction reactions: concepts and applications in organic chemistry
TL;DR: The concept of polarity reversal catalysis (PRC) was introduced in this paper to replace a single-step abstraction, that is slow because of unfavourable polar effects, with a two-step process in which the radicals and substrates are matched.
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A Case Study in Biomimetic Total Synthesis: Polyolefin Carbocyclizations to Terpenes and Steroids
TL;DR: I would like to give a warning, from a theoretical point of view, about all the carbonium ion mechanisms, that the human mind is not quick and clever as the enzyme.
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