Biomimetic radical ring expansion and aromatisation; a model for the biogenesis of natural ring-D aromatic steroids

1992 ◽  
pp. 1754 ◽  
Author(s):  
Stuart P. Green ◽  
Donald A. Whiting
Keyword(s):  
Ring Expansion ◽  
Radical Ring

ChemInform Abstract: Novel Free-Radical Ring-Expansion Reactions.

ChemInform ◽  
1989 ◽  
Vol 20 (21) ◽  
Author(s):  
P. DOWD ◽  
S.-C. CHOI
Keyword(s):  
Free Radical ◽  
Ring Expansion ◽  
Radical Ring

Free radical ring expansion and chain extension of 1,3-diketones

2005 ◽  
Vol 46 (28) ◽  
pp. 4727-4729 ◽  
Author(s):  
Xue-Jun Mu ◽  
Jian-Ping Zou ◽  
Zhi-Tao Wang ◽  
Wei Zhang
Keyword(s):  
Free Radical ◽  
Ring Expansion ◽  
Chain Extension ◽  
Radical Ring

Radical Tropolone Biosynthesis

2020 ◽  
Author(s):  
Tyler J. Doyon ◽  
Kevin Skinner ◽  
Di Yang ◽  
Leena Mallik ◽  
Troy Wymore ◽  
...  
Keyword(s):  
Active Site ◽  
Building Blocks ◽  
Ring Expansion ◽  
Heme Iron ◽  
Active Site Residues ◽  
Molecular Scaffolds ◽  
Radical Ring ◽  
Full Characterization ◽  
Dynamics Simulations ◽  
Functionally Diverse

<div> <div> <div> <p>Non-heme iron (NHI) enzymes perform a variety of oxidative rearrangements to advance simple building blocks toward complex molecular scaffolds within secondary metabolite pathways. Many of these transformations occur with selectivity that is unprecedented in small molecule catalysis, spurring an interest in the enzymatic processes which lead to a particular rearrangement. In-depth investigations of NHI mechanisms examine the source of this selectivity and can offer inspiration for the development of novel synthetic transformations. However, the mechanistic details of many NHI-catalyzed rearrangements remain underexplored, hindering full characterization of the chemistry accessible to this functionally diverse class of enzymes. For NHI-catalyzed rearrangements which have been investigated, mechanistic proposals often describe one-electron processes, followed by single electron oxidation from the substrate to the iron(III)-hydroxyl active site species. Here, we examine the ring expansion mechanism employed in fungal tropolone biosynthesis. TropC, an α-ketoglutarate- dependent NHI dioxygenase, catalyzes a ring expansion in the biosynthesis of tropolone natural product stipitatic acid through an under-studied mechanism. Investigation of both polar and radical mechanistic proposals suggests tropolones are constructed through a radical ring expansion. This biosynthetic route to tropolones is supported by X-ray crystal structure data combined with molecular dynamics simulations, alanine-scanning of active site residues, assessed reactivity of putative biosynthetic intermediates, and quantum mechanical (QM) calculations. These studies support a radical ring expansion in fungal tropolone biosynthesis. </p> </div> </div> </div>

Radical Tropolone Biosynthesis

2020 ◽  
Author(s):  
Tyler J. Doyon ◽  
Kevin Skinner ◽  
Di Yang ◽  
Leena Mallik ◽  
Troy Wymore ◽  
...  
Keyword(s):  
Active Site ◽  
Building Blocks ◽  
Ring Expansion ◽  
Heme Iron ◽  
Active Site Residues ◽  
Molecular Scaffolds ◽  
Radical Ring ◽  
Full Characterization ◽  
Dynamics Simulations ◽  
Functionally Diverse

<div> <div> <div> <p>Non-heme iron (NHI) enzymes perform a variety of oxidative rearrangements to advance simple building blocks toward complex molecular scaffolds within secondary metabolite pathways. Many of these transformations occur with selectivity that is unprecedented in small molecule catalysis, spurring an interest in the enzymatic processes which lead to a particular rearrangement. In-depth investigations of NHI mechanisms examine the source of this selectivity and can offer inspiration for the development of novel synthetic transformations. However, the mechanistic details of many NHI-catalyzed rearrangements remain underexplored, hindering full characterization of the chemistry accessible to this functionally diverse class of enzymes. For NHI-catalyzed rearrangements which have been investigated, mechanistic proposals often describe one-electron processes, followed by single electron oxidation from the substrate to the iron(III)-hydroxyl active site species. Here, we examine the ring expansion mechanism employed in fungal tropolone biosynthesis. TropC, an α-ketoglutarate- dependent NHI dioxygenase, catalyzes a ring expansion in the biosynthesis of tropolone natural product stipitatic acid through an under-studied mechanism. Investigation of both polar and radical mechanistic proposals suggests tropolones are constructed through a radical ring expansion. This biosynthetic route to tropolones is supported by X-ray crystal structure data combined with molecular dynamics simulations, alanine-scanning of active site residues, assessed reactivity of putative biosynthetic intermediates, and quantum mechanical (QM) calculations. These studies support a radical ring expansion in fungal tropolone biosynthesis. </p> </div> </div> </div>

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