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Open AccessJournal ArticleDOI

A twist of nature--the significance of atropisomers in biological systems.

Jamie E. Smyth, +2 more
- 21 Oct 2015 - 
- Vol. 32, Iss: 11, pp 1562-1583
TLDR
The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atrop isomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets.
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This article is published in Natural Product Reports.The article was published on 2015-10-21 and is currently open access. It has received 324 citations till now. The article focuses on the topics: Hibarimicinone.

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Citations
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Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

TL;DR: In this paper, the unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio using DFT, MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set.
Journal ArticleDOI

Recent Advances in Catalytic Asymmetric Construction of Atropisomers.

TL;DR: In this paper, a review summarizes key achievements in stereoselective preparation of biaryl, heterobiaryl, and non-biaryl atropisomers documented between 2015 and 2020.
Journal ArticleDOI

Atroposelective Synthesis of Axially Chiral Biaryls by Palladium-Catalyzed Asymmetric C−H Olefination Enabled by a Transient Chiral Auxiliary

TL;DR: Atroposelective synthesis of axially chiral biaryls by palladium-catalyzed C-H olefination, using tert-leucine as an inexpensive, catalytic, and transient chiral auxiliary has been realized.
Journal ArticleDOI

Recent advances in the synthesis of axially chiral biaryls via transition metal-catalysed asymmetric C–H functionalization

TL;DR: An overview of recent advances in the synthesis of axially chiral biaryl motifs via transition metal-catalysed asymmetric C-H functionalization is provided.
Journal ArticleDOI

General Enantioselective C-H Activation with Efficiently Tunable Cyclopentadienyl Ligands.

TL;DR: The three-step gram-scale synthesis of a structurally diverse and widely applicable chiral Cp ligand collection (JasCp ligands) with highly variable and adjustable structures is described.
References
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Journal ArticleDOI

Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields

TL;DR: In this article, the unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio using DFT, MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set.
Journal ArticleDOI

Atroposelective Synthesis of Axially Chiral Biaryl Compounds

TL;DR: This Review classifies strategies in the asymmetric synthesis of axially chiral biaryl compounds according to their underlying concepts and critically evaluates their scope and limitations with reference to selected model reactions and applications.
Journal ArticleDOI

Atroposelective total synthesis of axially chiral biaryl natural products.

TL;DR: Gerhard Bringmann's research interests focus on the field of analytical, synthetic, and computational natural product chemistry, i.e., on axially chiral biaryls, which is characterized by a broad structural diversity.
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Frequently Asked Questions (13)
Q1. What contributions have the authors mentioned in the paper "A twist of nature-the significance of atropisomers in biological systems" ?

Recently identified natural atropisomeric compounds with potential medicinal applications are presented in this paper, including hibarimicinone, flavomannin, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. 

given the specific tertiary structure of proteins, the geometric orientation of bioactive molecules is crucial to their ability to favourably interact with active and allosteric sites. 

Marinopyrrole derivatives with a cyclic structure and sulphide substituents have proven to be promising inhibitors of the interactions between proapoptotic proteins, Bcl-xL and Mcl-1, and their target pro-survival protein, Bim.64, 65, 74 It was also found that marinopyrrole A may restore activity of the anticancer drug ABT-737 to resistant cancer cells.75 

Alongside well-known vinca alkaloids, some naturally-occurring peptidic molecules elicit such inhibition, including the atropisomeric ustiloxin family of molecules, which target the α,β-tubulin dimer. 

The first successful approach in the generation of ustiloxin D was a linear total synthesis consisting of 31 steps, with an 82% yield on average for each step. 

such half-lives are determined using chiral HPLC at low temperatures, to evaluate the configurational stability of an atropisomer against inversion, though computational calculation of rotational energy barriers is also an effective technique. 

In 2011, Gottardi et al treated cultures of V. maris AB-18-032 with 13C-labelled precursors and found that abyssomicin C is biosynthetically produced from five acetates, two propionates, and a glycolytic pathway metabolite. 

vibrational circular dichroism (VCD) and vibrational absorption (VA) techniques were successful in the identification of point chirality in the atropisomeric cephalochromin.31 

There are various ab initio methods which may be applied,15 though the most common of these relies on optimizing the structures of the two predicted atropenantiomers with a density functional theory (DFT), then applying a time-dependent (TD) perturbation to predict the vibrational or electronic transitions. 

78 Analysis of the 1H-NMR spectrum of the unnamed dimer revealed it to be asymmetric by the presence of two sets of peaks, resulting in a total of eleven aromatic protons. 

The final yield of the native (P) atropisomer 5f was 22% from the enantiopure biaryl thiolactone 8, and could be quantitatively converted to the (M) form by heating to 60 °C in neutral methanol. 

Unlike stereogenicity arising from point chirality, which may only be altered through the breaking and reformation of chemical bonds, the configuration of atropisomers is governed primarily by their thermodynamic environment. 

It was in a study by Challis et al in 2010 that NOESY correlations of the HCl salts of extracted streptorubin B allowed for assignment of the major naturally occurring product as being the anticonfiguration with regards to the positioning of the C7ʹ n-butyl group relative to rings A and B, with the syn configuration only present in minor amounts.