Ryan P Pemberton

Ryan P Pemberton
Nurix, Inc. · Computational Chemistry

Ph.D., Chemistry

About

27
Publications
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508
Citations

Publications

Publications (27)
Article
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...
Article
Full-text available
The relative importance of preorganization, selective transition state stabilization and inherent reactivity are assessed through quantum chemical and docking calculations for a sesquiterpene synthase (epi-isozizaene synthase, EIZS). Inherent reactivity of the bisabolyl cation, both static and dynamic, appears to determine the pathway to product, a...
Article
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 f...
Article
Full-text available
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, w...
Article
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 bicyclo[2.2.1] and bicyclo[2.2.2] frameworks have distinct characteristic lifetimes, ca. 40...
Article
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 bo...
Article
Full-text available
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 bo...
Article
Full-text available
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 poten...
Article
Dynamics calculations are described for carbo- cation rearrangements involving product-forming pathways with post-transition state bifurcations. We show that noncovalent inter- actions with associated benzene rings—simple models of aromatic amino acid sidechains—can switch inherent dynamical tendencies for competing modes of disrotation, establishi...
Article
Human respiratory syncytial virus (RSV) is a negative-sense RNA virus and a significant cause of respiratory infection in infants and the elderly. No effective vaccines or antiviral therapies are available for the treatment of RSV. ALS-8176 is a first-in-class, nucleoside prodrug inhibitor of RSV replication currently under clinical evaluation. ALS...
Article
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...
Article
Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant α-ketoamides. Experimentally determined hydration equilibrium constants for related ketones and aldehydes were compared to computationally determined values to develop a method for predicting hydration equilibrium const...
Article
The focus is on the final synthetic step, the reaction between the key intermediates (I) and (II) yielding santalin Y (III).
Article
Full-text available
Quantum chemical calculations on the isomerization of 24-methylenecycloartanol are described. An energetically viable mechanism, with a rate-determining protonation step, is proposed. This rearrangement may find applicability in tests for determining if an olive oil has been refined. Graphical Abstract The results of density functional calculations...
Article
The development of the domino reaction between an aminoethyl-substituted diene and maleic anhydride to afford an N-substituted-octahydroisoquinolin-1-one is described. A typical procedure involves the treatment of a 1-aminoethyl-substituted butadiene with maleic anhydride at 0 degC to room temperature for 20 minutes under low-solvent conditions, wh...
Article
Santalin Y … …, a complex yet racemic natural product, has been prepared by a biomimetic total synthesis. D. J. Tantillo, D. Trauner et al. propose in their Communication on page 5079 ff. that the key step is a cascade involving a (3+2) cycloaddition and a Friedel–Crafts ring closure, which generates the unique oxafenestrane framework of santalin Y...
Article
Eine biomimetische Totalsynthese von Santalin Y, einem strukturell komplexen, jedoch racemischen Naturstoff, wird beschrieben. Ihr Schlüsselschritt ist eine (3+2)-Cycloaddition eines Benzylstilbens an ein “vinyloges Oxidopyrylium”, gefolgt von einer intramolekularen Friedel-Crafts-Reaktion. Diese Kaskade erzeugt das einzigartige Oxafenestran-Gerüst...
Article
Santalin Y … …, ein komplexer racemischer Naturstoff, wurde über eine biomimetische Totalsynthese hergestellt. D. J. Tantillo, D. Trauner et al. identifizieren in der Zuschrift auf S. 5168 ff. als den Schlüsselschritt eine Kaskade aus (3+2)-Cycloaddition und Friedel-Crafts-Ringschluss, die das einzigartige Oxafenestran-Gerüst von Santalin Y aufbaut...
Article
Full-text available
In molecular sciences, articles tend to revolve around 2D representations of 3D molecules, and sighted scientists often resort to 3D virtual reality software to study these molecules in detail. Blind and visually impaired (BVI) molecular scientists have access to a series of audio devices that can help them read the text in articles and work with c...
Article
Although evidence has mounted in recent years for the biosynthetic relevance of [4+2] cycloaddition reactions, other cycloadditions have received much less attention. Herein we use density functional theory (DFT) calculations to assess the viability of nitrone-alkene (3+2) cycloaddition reactions proposed to occur during the biosynthesis of several...
Article
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...
Article
DFT (both B3LYP and M06-2X), CASSCF, and CASPT2 calculations were used to investigate competing [3, 3] and [3, 5] sigmatropic shifts and intramolecular [4+2] cycloaddition of 1,3,7-octatriene. In accord with previous results on 1,5-hexadiene, CASSCF calculations found both stepwise and concerted pathways for the [3, 3] rearrangement. For the compet...
Article
Anhydrous HBr used in reactive ion etch chemistries for the semiconductor industry requires strict control of impurities over time. Proper selection of cylinder materials strongly influences the purity of the HBr over the shelf life of the stored gas. In this work Ni-lined AISI 4130 Cr-Mo steel cylinders are compared to the gas industry standard AI...
Article
For both [4n] and [4n + 2]annulenes, cases of configuration change in which the number of trans C=C bonds changes by 1 must involve a Mobius -bond shifting step. The known configuration change in [14]annulene (1, CTCTCTT -> 2, CCTCTCT), for which delta trans = 1, is thus predicted to involve a Mobius antiaromatic transition state for bond shifting....
Article
Density functional and ab initio methods have been used to study the mechanisms for key dynamic processes of the experimentally known S4-symmetric [16]annulene (1a). Using BH&HLYP/6-311+G** and B3LYP/6-311+G**, we located two viable stepwise pathways with computed energy barriers (Ea = 8-10 kcal/mol) for conformational automerization of 1a, in agre...
Article
We report density-functional and coupled-cluster calculations on conformation change and degenerate bond shifting in [10]annulene isomers 1-5. At the CCSD(T)/cc-pVDZ//CCSD/6-31G level, conversion of the twist (1) to the heart (2) has a barrier of 10.1 kcal/mol, compared to Ea = 16.2 kcal/mol for degenerate "two-twist" bond shifting in 1. Pseudorota...
Article
Density functional and coupled cluster calculations show that facile thermal configuration change in [12]annulene occurs via a twist-coupled bond-shifting mechanism. The transition state for this process is highly aromatic with Möbius topology. At the CCSD(T)/cc-pVDZ//BH&HLYP/6-311+G** level, the isomerization of tri-trans-[12]annulene 1a (CTCTCT)...