Disorderly Conduct of Benzamide IV: Crystallographic and Computational Analysis of High Entropy Polymorphs of Small Molecules

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

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Bis(pentafluorophenyl)phenothiazylborane – A Pseudo Frustrated Radical Pair for the Catalytic Dehydrocoupling of Stannanes

10.26434/chemrxiv.11796129.v1 ◽

2020 ◽

Author(s):

Jordan N. Bentley ◽

Ekadashi Pradhan ◽

Tao Zeng ◽

Christopher B. Caputo

Keyword(s):

Small Molecules ◽

Computational Analysis ◽

Bond Activation ◽

Radical Pair ◽

Frustrated Lewis Pairs ◽

Frustrated Lewis Pair ◽

Lewis Pairs

The understanding of the mechanism by which frustrated Lewis pairs activate small molecules has been evolving with the discovery that both heterolytic and homolytic bond activation is possible. Herein we characterized a novel Lewis acidic aminoborane containing a phenothiazyl substituent and demonstrate its potential to catalytically promote the dehydrocoupling of tin hydrides. The reactivity observed implies this species promotes homolytic bond activation, however computational analysis suggests a heterolytic mechanism for this reaction. This result represents the first frustrated Lewis pair system to blur the lines between heterolytic and homolytic reactivity.

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Assessing electronic properties of desymmetrized heterocyclic patterns: towards tuning small molecules for photovoltaic applications

MRS Advances ◽

10.1557/adv.2020.434 ◽

2020 ◽

Vol 5 (61) ◽

pp. 3171-3184

Author(s):

Oscar González-Antonio ◽

Rebeca Yépez ◽

María Magdalena Vázquez-Alvarado ◽

Blas Flores-Pérez ◽

Norberto Farfán ◽

...

Keyword(s):

Small Molecules ◽

Heterocyclic Compounds ◽

Computational Analysis ◽

Organic Molecules ◽

Spectroscopic Properties ◽

Small Organic Molecules ◽

Photovoltaic Materials ◽

Photovoltaic Applications ◽

Donor Acceptor ◽

Homo Lumo

AbstractA series of highly attainable desymmetrized heterocyclic compounds with Donor-Acceptor-Donor-Acceptor-X (D-A-D-X) architectures were synthesized. The structures, where X corresponds to a heteroaromatic portion (pyridine, ferrocene, thiadiazolopyridine), were designed through computational analysis. Molecular geometries for all compounds were studied and parameters of charge transfer were computed in order to analyse the behaviour in each architecture. Spectroscopic properties (maximum absorption wavelengths, extinction coefficients and HOMO-LUMO gaps) were predicted and measured experimentally. UV-Vis absorption profiles and values of HOMO-LUMO optical gaps (in the vicinity of 2.0 eV), together with the computational results, are properties that position the obtained systems, as potential candidates for developing efficient photovoltaic materials based on synthetically accessible small organic molecules.

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Bis(pentafluorophenyl)phenothiazylborane – A Pseudo Frustrated Radical Pair for the Catalytic Dehydrocoupling of Stannanes

10.26434/chemrxiv.11796129 ◽

2020 ◽

Author(s):

Jordan N. Bentley ◽

Ekadashi Pradhan ◽

Tao Zeng ◽

Christopher B. Caputo

Keyword(s):

Small Molecules ◽

Computational Analysis ◽

Bond Activation ◽

Radical Pair ◽

Frustrated Lewis Pairs ◽

Frustrated Lewis Pair ◽

Lewis Pairs

The understanding of the mechanism by which frustrated Lewis pairs activate small molecules has been evolving with the discovery that both heterolytic and homolytic bond activation is possible. Herein we characterized a novel Lewis acidic aminoborane containing a phenothiazyl substituent and demonstrate its potential to catalytically promote the dehydrocoupling of tin hydrides. The reactivity observed implies this species promotes homolytic bond activation, however computational analysis suggests a heterolytic mechanism for this reaction. This result represents the first frustrated Lewis pair system to blur the lines between heterolytic and homolytic reactivity.

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Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

10.26434/chemrxiv.7322330 ◽

2018 ◽

Author(s):

Timothy Newhouse ◽

Daria E. Kim ◽

Joshua E. Zweig

Keyword(s):

Chemical Synthesis ◽

Total Synthesis ◽

Small Molecules ◽

First Principles ◽

Quantum Chemical ◽

Computational Analysis ◽

Empirical Evaluation ◽

Synthetic Strategy ◽

Catalyzed Reactions ◽

Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

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Pd(II)-catalyzed enantioselective C(sp3)–H arylation of cy-clopropanes and cyclobutanes guided by tertiary alkyla-mines.

10.26434/chemrxiv-2021-g856r ◽

2021 ◽

Author(s):

Matthew Gaunt ◽

Jesus Rodrigalvarez ◽

Luke Reeve ◽

Javier Miro

Keyword(s):

Small Molecules ◽

Computational Analysis ◽

Structural Features ◽

Biological Properties ◽

Boronic Acids ◽

Biologically Active ◽

Simple Method ◽

Amino Acid Ligand ◽

Acid Ligand ◽

Palladium Catalyzed

ABSTRACT: Strained aminomethyl-cycloalkanes are a recurrent scaffold in medicinal chemistry due to their unique structural features that give rise to a range of biological properties. Here, we report a palladium-catalyzed enantioselective C(sp3)–H arylation of aminome-thyl-cyclopropanes and -cyclobutanes with aryl boronic acids. A range of native tertiary alkylamine groups are able to direct C–H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios. Cen-tral to the success of this strategy is the use of a simple N-acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes -C–H activation of over other pathways. Computational analysis of the cyclopalladation step provides an understanding of how enantioselective C–H cleavage occurs and revealed distinct transition structures to our previous work on enantioselective desymme-trization of N-iso-butyl tertiary alkylamines. This straightforward and operationally simple method simplifies the construction of func-tionalized aminomethyl-strained cycloalkanes, which we believe will find widespread use in academic and industrial settings relating to the synthesis of biologically active small molecules.

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Gap junctions in the prothoracic glands of the tobacco hornworm, Manduca sexta

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123933 ◽

1992 ◽

Vol 50 (1) ◽

pp. 706-707

Author(s):

Ji-da Dai ◽

M. Joseph Costello ◽

Lawrence I. Gilbert

Keyword(s):

Gap Junctions ◽

Small Molecules ◽

Manduca Sexta ◽

Freeze Fracture ◽

Cell Communication ◽

Cellular Level ◽

Thin Sections ◽

Prothoracic Glands ◽

Polyhydroxylated Steroids ◽

Stimulation Of

Insect molting and metamorphosis are elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands (PGs). Prothoracicotropic hormone stimulation of steroidogenesis by the PGs at the cellular level involves both calcium and cAMP. Cell-to-cell communication mediated by gap junctions may play a key role in regulating signal transduction by controlling the transmission of small molecules and ions between adjacent cells. This is the first report of gap junctions in the PGs, the evidence obtained by means of SEM, thin sections and freeze-fracture replicas.

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Fusion and Fission Processes in Exocytosis: Possible Roles for Synexin and Osmotic Lysis in the Two Events

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002634 ◽

1980 ◽

Vol 38 ◽

pp. 594-597

Author(s):

H.B. Pollard ◽

C.E. Creutz ◽

C.J. Pazoles ◽

J.H. Scott

Keyword(s):

Small Molecules ◽

Chromaffin Cells ◽

Adrenal Glands ◽

General Concept ◽

Extracellular Calcium ◽

Large Protein ◽

Granule Membrane ◽

Osmotic Lysis ◽

Per Se ◽

Chemical Evidence

Exocytosis is a general concept describing secretion of enzymes, hormones and transmitters that are otherwise sequestered in intracellular granules. Chemical evidence for this concept was first gathered from studies on chromaffin cells in perfused adrenal glands, in which it was found that granule contents, including both large protein and small molecules such as adrenaline and ATP, were released together while the granule membrane was retained in the cell. A number of exhaustive reviews of this early work have been published and are summarized in Reference 1. The critical experiments demonstrating the importance of extracellular calcium for exocytosis per se were also first performed in this system (2,3), further indicating the substantial service given by chromaffin cells to those interested in secretory phenomena over the years.

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