Dynamics calculations are described for carbocation rearrangements involving product-forming pathways with post-transition-state bifurcations. We show that noncovalent interactions with associated ...benzene rings (a simple model of aromatic amino acid side chains) can switch inherent dynamical tendencies for competing modes of disrotation, establishing that meaningful changes in dynamically controlled product selectivity can be achieved with few weak noncovalent interactions.
Although the aromatic aza-Claisen rearrangement is a general strategy for accessing substituted aromatic amines, there are no highly enantioselective examples of this process. We report the first ...Brønsted acid catalyzed enantioselective indole aza-Claisen rearrangement for the synthesis of chiral 3-amino-2-substituted indoles. We present evidence for an arene CH–O interaction as a source of activation and stereoinduction, which is an unprecedented phenomenon in enantioselective Brønsted acid catalysis. The products of this reaction can be transformed into 3-aminooxindoles, which are prevalent in many biologically active small molecules.
Biomimetic Total Synthesis of Santalin Y Strych, Sebastian; Journot, Guillaume; Pemberton, Ryan P. ...
Angewandte Chemie (International ed.),
April 20, 2015, Letnik:
54, Številka:
17
Journal Article
Recenzirano
A biomimetic total synthesis of santalin Y, a structurally complex but racemic natural product, is described. The key step is proposed to be a (3+2) cycloaddition of a benzylstyrene to a “vinylogous ...oxidopyrylium”, which is followed by an intramolecular Friedel–Crafts reaction. This cascade generates the unique oxafenestrane framework of the target molecule and sets its five stereocenters in one operation. Our work provides rapid access to santalin Y and clarifies its biosynthetic relationship with other colorants isolated from red sandalwood.
High five! The five stereocenters of santalin Y, a complex yet racemic natural product, were installed in a single operation. Quantum chemical computations point to a concerted 1,3‐dipoar cycloaddition that involves a “vinylogous oxidopyrylium species” as the key step.
Computational chemistry approaches for studying the formation of terpenes/terpenoids in wines are presented, using five particular terpenes/terpenoids (1,8-cineole, α-ylangene, botrydial, rotundone, ...and the wine lactone), volatile compounds (or their precursors) found in wine and/or wine grapes, as representative examples. Through these examples, we show how modern computational quantum chemistry can be employed as an effective tool for assessing the validity of proposed mechanisms for terpene/terpenoid formation.
Tetrafluoroethylene and butadiene form the 2 + 2 cycloadduct under kinetic control, but the Diels–Alder cycloadduct is formed under thermodynamic control. Borden and Getty showed that the preference ...for 2 + 2 cycloaddition is due to the necessity for syn-pyramidalization of the two CF2 groups in the 4 + 2 transition state. We have explored the full potential energy surface for the concerted and stepwise reactions of tetrafluoroethylene and butadiene with density functional theory, DFT (B3LYP and M06-2X), DLPNO-UCCSD(T), and CASSCF-NEVPT2 methods and with the distortion/interaction–activation strain model to explain the energetics of different pathways. The 2 + 2 cycloadduct is formed by an anti-transition state followed by two rotations and a final bond formation transition state. Energetics are compared to the reaction of maleic anhydride and ethylene.
The lifetimes of secondary carbocations proposed to occur along reaction coordinates for terpene-forming carbocation rearrangements were estimated from direct dynamics simulations using density ...functional theory. Classical secondary carbocations supported by bicyclo2.2.1 and bicyclo2.2.2 frameworks have distinct characteristic lifetimes,
ca.
40 and 90 fs, respectively. The fusion of additional rings to these frameworks was found to have little effect on these lifetimes, despite altering the potential energy surfaces for rearrangement. Inherent dynamical tendencies of secondary carbocations are shown to be manipulable by alkylation and enforced intermolecular interactions.
The lifetimes of secondary carbocations proposed to occur along reaction coordinates for terpene-forming carbocation rearrangements were estimated from direct dynamics simulations using density functional theory.
The relative importance of preorganization, selective transition state stabilization and inherent reactivity are assessed through quantum chemical and docking calculations for a sesquiterpene ...synthase (
-isozizaene synthase, EIZS). Inherent reactivity of the bisabolyl cation, both static and dynamic, appears to determine the pathway to product, although preorganization and selective binding of the final transition state structure in the multi-step carbocation cascade that forms
-isozizaene appear to play important roles.
The enantioselective total syntheses of himandravine and GB17 were completed through a common biomimetic strategy involving Diels–Alder reactions of unusual double diene containing linear precursors. ...The double diene precursors, containing or lacking a C12 substituent as required to produce GB17 or himandravine, respectively, were found to undergo Diels–Alder reactions to afford mixtures of regioisomeric cycloadducts that map onto the alternative carbocyclic frameworks of both himandravine and GB17. Computational investigations revealed that these Diels–Alder reactions proceed via transition state structures of similar energy that have a high degree of bispericyclic character and that the low levels of regioselectivity observed in the reactions are a consequence of competing orbital interaction and distortion energies. The combined experimental and computational results provide valuable insights into the biosynthesis of the Galbulimima alkaloids.
Chlorophyll and heme are among the “pigments of life”, tetrapyrrolic structures, without which life on Earth would not be possible. Their catabolites, the phyllobilins and the bilins, respectively, ...share not only structural features, but also a similar story: Long considered waste products of detoxification processes, important bioactivities for both classes have now been demonstrated. For phyllobilins, however, research on physiological roles is sparse. Here, we introduce actin, the major component of the cytoskeleton, as the first discovered target of phyllobilins and as a novel target of bilins. We demonstrate the inhibition of actin dynamics in vitro and effects on actin and related processes in cancer cells. A direct interaction with G‐actin is shown by in silico studies and confirmed by affinity chromatography. Our findings open a new chapter in bioactivities of tetrapyrroles—especially phyllobilins—for which they form the basis for broad implications in plant science, ecology, and physiology.
The physiological role of the degradation products of chlorophyll and heme, exogenous phyllobilins and endogenous bilins, respectively, remained an unsolved mystery for decades. We describe the influence of these tetrapyrroles on the actin cytoskeleton and introduce G‐actin as the first human target protein for phyllobilins and a novel target for bilins. This study opens up a new perspective of the importance of these ubiquitous natural products.
An introduction to the application of quantum chemical dynamics calculations to mechanistic problems in the field of terpene biosynthesis is provided. A bare bones introduction to the fundamentals of ...chemical dynamics is followed by a brief account of previous applications to terpene-forming carbocation reactions, a discussion of questions in this field that dynamics calculations may help answer, and a description of current problems to which dynamics calculations are being applied.
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![Concerted [4 + 2] and Stepw...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0022-3263_1520-6904/small "Concerted [4 + 2] and Stepwise (2 + 2) Cycloadditions of Tetrafluoroethylene with Butadiene: DFT and DLPNO-UCCSD(T) Explorations")
