33 results on '"Babak Borhan"'
Search Results
2. A Lewis Acid-Controlled Enantiodivergent Epoxidation
- Author
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Aliakbar Mohammadlou, Chetan Joshi, Brendyn Smith, Li Zheng, Virginia Canestraight, Saeedeh Torabikohlbouni, Maryamdokht Taimoory, Stephanie Corio, Babak Borhan, Richard Staples, Mathew Vetticatt, and William Wulff
- Abstract
Two epoxidation catalysts one of which consists of two VANOL ligands and an aluminum and the other of two VANOL ligands and a boron were compared. Both catalysts are highly effective in the catalytic asymmetric epoxidation of a variety of aromatic and aliphatic aldehydes with diazoacetamides giving high yields and excellent asymmetric inductions. The aluminum catalyst is effective at 0 °C and the boron catalyst at –40 °C. Although both the aluminum and boron catalysts of (R)-VANOL give very high asymmetric inductions (up to 99% ee), they give opposite enantiomers of the epoxide. The mechanism, rate- and enantioselectivity-determining step, and origin of enantiodivergence is evaluated using DFT calculations.
- Published
- 2023
3. Structure Guided Design of VANOL-imidodiphosphorimidate Catalysts for the Catalytic Enantioselective Bromo Spiroketalization Reaction
- Author
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Aliakbar Mohammadlou, Ankush Chakraborty, Mitchell Maday, Xiaopeng Yin, Li Zheng, Hadi Gholami, Kumar Ashtekar, Richard Staples, William Wulff, and Babak Borhan
- Abstract
This report presents a structure-guided approach for the optimization of VANOL-derived imidodiphosphorimidates as catalysts for the halonium-ion-induced spiroketalization reaction. Fine tuning of the catalyst active site, alongside enhanced acidity, were required to achieve high catalytic activity for the spiroketalization reaction. A wide range of substrates were well tolerated yielding halogenated spiroketals in high yields, diastereoselectivities, and enantioselectivities.
- Published
- 2023
4. Structure–Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts
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Sarah E. Luderer, Behrad Masoudi, Aritra Sarkar, Calvin Grant, Arvind Jaganathan, James E. Jackson, and Babak Borhan
- Subjects
Organic Chemistry - Published
- 2023
5. Excited-State Dynamics of a Substituted Fluorene Derivative. The Central Role of Hydrogen Bonding Interactions with the Solvent
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James E. Jackson, Piotr Piecuch, Mehdi Moemeni, Aria Vahdani, Soham Maity, Babak Borhan, Marcos Dantus, Stephen H. Yuwono, Gary J. Blanchard, and Briana A. Capistran
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Fluorenes ,Chemistry ,Hydrogen bond ,Relaxation (NMR) ,Hydrogen Bonding ,Electronic structure ,Fluorene ,Photochemistry ,Article ,Surfaces, Coatings and Films ,Solvent ,chemistry.chemical_compound ,Spectrometry, Fluorescence ,Excited state ,Solvents ,Materials Chemistry ,Molecule ,Physical and Theoretical Chemistry ,Schiff Bases ,Derivative (chemistry) - Abstract
Substituted fluorene structures have demonstrated unusual photochemical properties. Previous reports on the substituted fluorene Schiff base FR0-SB demonstrated super photobase behavior with a ΔpK(b) of ~14 upon photoexcitation. In an effort to understand the basis for this unusual behavior, we have examined the electronic structure and relaxation dynamics of the structural precursor of FR0-SB, the aldehyde FR0, in protic and aprotic solvents using time-resolved fluorescence spectroscopy and quantum chemical calculations. The calculations show three excited singlet states in relatively close energetic proximity. The spectroscopic data are consistent with relaxation dynamics from these electronic states that depend on the presence and concentration of solvent hydroxyl functionality. These results underscore the central role of solvent hydrogen bonding to the FR0 aldehyde oxygen in mediating the relaxation dynamics within this molecule.
- Published
- 2021
6. Computational and Spectroscopic Characterization of the Photocycle of an Artificial Rhodopsin
- Author
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Adam J. Jenkins, Yoelvis Orozco-Gonzalez, Babak Borhan, James H. Geiger, Massimo Olivucci, Delmar S. Larsen, Madushanka Manathunga, and Alireza Ghanbarpour
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Rhodopsin ,Light ,Photoisomerization ,Double bond ,Receptors, Retinoic Acid ,Retinoic Acid ,Protonation ,Photochemistry ,Article ,chemistry.chemical_compound ,Isomerism ,Receptors ,Ultrafast laser spectroscopy ,General Materials Science ,Physical and Theoretical Chemistry ,Eye Disease and Disorders of Vision ,Schiff Bases ,chemistry.chemical_classification ,Schiff base ,biology ,Spectrum Analysis ,Neurosciences ,Retinal ,chemistry ,Physical Sciences ,Chemical Sciences ,biology.protein ,Quantum Theory ,Isomerization - Abstract
The photocycle of a reversible photoisomerizing rhodopsin mimic (M2) is investigated. This system, based on the cellular retinoic acid binding protein, is structurally different from natural rhodopsin systems, but exhibits a similar isomerization upon light irradiation. More specifically, M2 displays a 15-cis to all-trans conversion of retinal protonated Schiff base (rPSB) and all-trans to 15-cis isomerization of unprotonated Schiff base (rUSB). Here we use hybrid quantum mechanics/molecular mechanics (QM/MM) tools coupled with transient absorption and cryokinetic UV–vis spectroscopies to investigate these isomerization processes. The results suggest that primary rPSB photoisomerization of M2 occurs around the C13=C14 double bond within 2 ps following an aborted-bicycle pedal (ABP) isomerization mechanism similar to natural microbial rhodopsins. The rUSB isomerization is much slower and occurs within 48 ps around the C15=N double bond. Our findings reveal the possibility to engineer naturally occurring mechanistic features into artificial rhodopsins and also constitute a step toward understanding the photoisomerization of UV pigments. We conclude by reinforcing the idea that the presence of the retinal chromophore inside a tight protein cavity is not mandatory to exhibit ABP mechanism.
- Published
- 2020
7. Mechanistic Insights into the Origin of Stereoselectivity in an Asymmetric Chlorolactonization Catalyzed by (DHQD)2PHAL
- Author
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Kumar Dilip Ashtekar, Daniel Holmes, Babak Borhan, Aritra Sarkar, James E. Jackson, Paul Reed, Tayeb Kakeshpour, Daniel C. Whitehead, and Roozbeh Yousefi
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chemistry.chemical_classification ,Olefin fiber ,Substrate (chemistry) ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,Colloid and Surface Chemistry ,chemistry ,Nucleophile ,Computational chemistry ,Electrophile ,Stereoselectivity ,Selectivity ,Lactone - Abstract
Electrophilic halofunctionalization reactions have undergone a resurgence sparked by recent discoveries in the field of catalytic asymmetric halocyclizations. To build mechanistic understanding of these asymmetric transformations, a toolbox of analytical methods has been deployed, addressing the roles of catalyst, electrophile (halenium donor), and nucleophile in determining rates and stereopreferences. The test reaction, (DHQD)2PHAL-catalyzed chlorocyclization of 4-arylpent-4-enoic acid with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), is revealed to be first order in catalyst and chlorenium ion donor and zero order in alkenoic acid substrate under synthetically relevant conditions. The simplest interpretation is that rapid substrate-catalyst binding precedes rate-limiting chlorenium attack, controlling the face selectivity of both chlorine attack and lactone closure. ROESY and DFT studies, aided by crystal structures of carboxylic acids bound by the catalyst, point to a plausible resting state of the catalyst-substrate complex predisposed for asymmetric chlorolactonization. As revealed by our earlier labeling studies, these findings suggest modes of binding in the (DHQD)2PHAL chiral pocket that explain the system's remarkable control over rate- and enantioselection-determining events. Though a comprehensive modeling analysis is beyond the scope of the present work, quantum chemical analysis of the fragments' interactions and candidate reaction paths point to a one-step concerted process, with the nucleophile playing a critical role in activating the olefin for concomitant electrophilic attack.
- Published
- 2020
8. Utilizing an enantioselective chloroetherification strategy towards the total synthesis of napyradiomycin A1
- Author
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Babak Borhan, Natasha Perry, Gonzalo Javier Villegas Rodríguez, Arvind Jaganathan, and Saeedeh Torabi Kohlbouni
- Published
- 2021
9. Proton Abstraction Mediates Interactions between the Super Photobase FR0-SB and Surrounding Alcohol Solvent
- Author
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James E. Jackson, Marcos Dantus, Jurick Lahiri, Mehdi Moemeni, Gary J. Blanchard, Jessica Kline, Piotr Piecuch, Stephen H. Yuwono, Ilias Magoulas, and Babak Borhan
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Models, Molecular ,Population ,Molecular Conformation ,Protonation ,010402 general chemistry ,Photochemistry ,01 natural sciences ,chemistry.chemical_compound ,Deprotonation ,0103 physical sciences ,Materials Chemistry ,Physical and Theoretical Chemistry ,education ,education.field_of_study ,010304 chemical physics ,Chemistry ,Intermolecular force ,Solvation ,Hydrogen Bonding ,Hydrogen-Ion Concentration ,0104 chemical sciences ,Surfaces, Coatings and Films ,Solvent ,Alcohols ,Excited state ,Solvents ,Thermodynamics ,Protons ,Ethylene glycol - Abstract
We report on the motional and proton transfer dynamics of the super photobase FR0-SB in the series of normal alcohols C1 (methanol) through C8 (n-octanol) and ethylene glycol. Steady-state and time-resolved fluorescence data reveal that the proton abstraction dynamics of excited FR0-SB depend on the identity of the solvent and that the transfer of the proton from solvent to FR0-SB*, forming FR0-HSB+*, fundamentally alters the nature of interactions between the excited molecule and its surroundings. In its unprotonated state, solvent interactions with FR0-SB* are consistent with slip limit behavior, and in its protonated form, intermolecular interactions are consistent with a much stronger interaction of FR0-HSB+* with the deprotonated solvent RO–. We understand the excited-state population dynamics in the context of a kinetic model involving a transition state wherein FR0-HSB+* is still bound to the negatively charged alkoxide, prior to solvation of the two charged species. Data acquired in ethylene glyco...
- Published
- 2019
10. Cu-Catalyzed Oxidation of C2 and C3 Alkyl-Substituted Indole via Acyl Nitroso Reagents
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Saeedeh Torabi Kohlbouni, Babak Borhan, and Jun Zhang
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Indoles ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Catalysis ,Article ,chemistry.chemical_compound ,Molecule ,Physical and Theoretical Chemistry ,Alkyl ,Amination ,Indole test ,chemistry.chemical_classification ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Nitroso ,Oxindoles ,0104 chemical sciences ,Reagent ,Alkyl substitution ,Oxidation-Reduction ,Copper ,Nitroso Compounds - Abstract
The selective oxidation of C2-alkyl-substituted indoles to 3-oxindole and the selective C─H oxygenation or amination of C2,C3-dialkyl-substituted indoles at C2 are reported under mild conditions. The position of the alkyl substitution on the indole directs the reaction to different pathways under similar conditions.
- Published
- 2018
11. Free-Energy-Based Protein Design: Re-Engineering Cellular Retinoic Acid Binding Protein II Assisted by the Moveable-Type Approach
- Author
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Haizhen A. Zhong, Zheng Zheng, Chrysoula Vasileiou, Elizabeth M. Santos, James H. Geiger, Kenneth M. Merz, and Babak Borhan
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0301 basic medicine ,Receptors, Retinoic Acid ,Protein design ,Molecular Dynamics Simulation ,Ligands ,Protein Engineering ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,Catalysis ,03 medical and health sciences ,Molecular dynamics ,Colloid and Surface Chemistry ,Cellular Retinoic Acid-Binding Protein II ,Binding site ,Retinoic acid binding ,Receptor ,Chemistry ,Mutagenesis ,General Chemistry ,Protein engineering ,0104 chemical sciences ,030104 developmental biology ,Biophysics ,Thermodynamics - Abstract
How to fine-tune the binding free energy of a small-molecule to a receptor site by altering the amino acid residue composition is a key question in protein engineering. Indeed, the ultimate solution to this problem, to chemical accuracy (±1 kcal/mol), will result in profound and wide-ranging applications in protein design. Numerous tools have been developed to address this question using knowledge-based models to more computationally intensive molecular dynamics simulations-based free energy calculations, but while some success has been achieved there remains room for improvement in terms of overall accuracy and in the speed of the methodology. Here we report a fast, knowledge-based movable-type (MT)-based approach to estimate the absolute and relative free energy of binding as influenced by mutations in a small-molecule binding site in a protein. We retrospectively validate our approach using mutagenesis data for retinoic acid binding to the Cellular Retinoic Acid Binding Protein II (CRABPII) system and then make prospective predictions that are borne out experimentally. The overall performance of our approach is supported by its success in identifying mutants that show high or even sub-nano-molar binding affinities of retinoic acid to the CRABPII system.
- Published
- 2018
12. Computationally Aided Absolute Stereochemical Determination of Enantioenriched Amines
- Author
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Minji Chun, Babak Borhan, Chrysoula Vasileiou, Xin-Liang Ding, Tatsuo Nehira, Hadi Gholami, and Jun Zhang
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Circular dichroism ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Computational chemistry ,Physical and Theoretical Chemistry ,Chiral derivatizing agent ,Enantiomeric excess ,Chiral amine - Abstract
A simple and efficient protocol for sensing the absolute stereochemistry and enantiomeric excess of chiral monoamines is reported. Preparation of the sample requires a single-step reaction of the 1,1'-(bromomethylene)dinaphthalene (BDN) with the chiral amine. Analysis of the exciton coupled circular dichroism generated from the BDN-derivatized chiral amine sample, along with comparison to conformational analysis performed computationally, yields the absolute stereochemistry of the parent chiral monoamine.
- Published
- 2017
13. A Photoisomerizing Rhodopsin Mimic Observed at Atomic Resolution
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Meisam Nosrati, James H. Geiger, Tetyana Berbasova, Chrysoula Vasileiou, and Babak Borhan
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Models, Molecular ,0301 basic medicine ,Rhodopsin ,Opsin ,genetic structures ,Photoisomerization ,Protein Conformation ,Receptors, Retinoic Acid ,Imine ,Molecular Conformation ,Protein Engineering ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,Article ,Catalysis ,03 medical and health sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Protein structure ,Isomerism ,Biomimetic Materials ,Humans ,biology ,Chemistry ,Bacteriorhodopsin ,General Chemistry ,Chromophore ,Photochemical Processes ,0104 chemical sciences ,030104 developmental biology ,Mutation ,biology.protein ,sense organs ,Isomerization - Abstract
The members of the rhodopsin family of proteins are involved in many essential light-dependent processes in biology. Specific photoisomerization of the protein-bound retinylidene PSB at a specified wavelength range of light is at the heart of all of these systems. Nonetheless, it has been difficult to reproduce in an engineered system. We have developed rhodopsin mimics, using intracellular lipid binding protein family members as scaffolds, to study fundamental aspects of protein/chromophore interactions. Herein we describe a system that specifically isomerizes the retinylidene protonated Schiff base both thermally and photochemically. This isomerization has been characterized at atomic resolution by quantitatively interconverting the isomers in the crystal both thermally and photochemically. This event is accompanied by a large pK(a) change of the imine similar to the pK(a) changes observed in bacteriorhodopsin and visual opsins during isomerization.
- Published
- 2016
14. Point-to-Axial Chirality Transfer—A New Probe for 'Sensing' the Absolute Configurations of Monoamines
- Author
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Kumar Dilip Ashtekar, Robert Acho, Mercy Anyika, Babak Borhan, and Hadi Gholami
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Steric effects ,Chemistry ,Stereochemistry ,Diastereomer ,General Chemistry ,Dichroic glass ,Biochemistry ,Helicity ,Catalysis ,Colloid and Surface Chemistry ,Molecular recognition ,Axial chirality ,Chemical physics ,Molecule ,Physics::Chemical Physics ,Chirality (chemistry) - Abstract
A host molecule, capable of freely adopting P or M helicity, is described for molecular recognition and chirality sensing. The host, consisting of a biphenol core, binds chiral amines via hydrogen-bonding interactions. The diastereomeric complex will favor either P or M helicity as a result of minimizing steric interactions of the guest molecule with the binding cavity of the host, resulting in a detectable exciton-coupled circular dichroic spectrum. A working model is proposed that enables non-empirical prediction of the chirality of the bound amine.
- Published
- 2014
15. Quantification of Competing H3PO4 Versus HPO3 + H2O Neutral Losses from Regioselective 18O-Labeled Phosphopeptides
- Author
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Babak Borhan, Ipek Yapici, Li Cui, and Gavin E. Reid
- Subjects
Phosphopeptides ,Phosphorous Acids ,Stereochemistry ,Carboxylic acid ,Molecular Sequence Data ,Protonation ,Peptide ,Oxygen Isotopes ,Tandem mass spectrometry ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,Structural Biology ,Peptide synthesis ,Phosphoric Acids ,Amino Acid Sequence ,Spectroscopy ,chemistry.chemical_classification ,Chromatography ,Phosphopeptide ,Water ,Stereoisomerism ,Peptide Fragments ,Amino acid ,chemistry ,Isotope Labeling ,Ion trap - Abstract
Abundant neutral losses of 98 Da are often observed upon ion trap CID-MS/MS of protonated phosphopeptide ions. Two competing fragmentation pathways are involved in this process, namely, the direct loss of H3PO4 from the phosphorylated residue and the combined losses of HPO3 and H2O from the phosphorylation site and from an additional site within the peptide, respectively. These competing pathways produce product ions with different structures but the same m/z values, potentially limiting the utility of CID-MS(3) for phosphorylation site localization. To quantify the relative contributions of these pathways and to determine the conditions under which each pathway predominates, we have examined the ion trap CID-MS/MS fragmentation of a series of regioselective (18)O-phosphate ester labeled phosphopeptides prepared using novel solution-phase amino acid synthesis and solid-phase peptide synthesis methodologies. By comparing the intensity of the -100 Da (-H3PO3 (18)O) versus -98 Da (-[HPO3 + H2O]) neutral loss product ions formed upon MS/MS, quantification of the two pathways was achieved. Factors that affect the extent of formation of the competing neutral losses were investigated, with the combined loss pathway predominantly occurring under conditions of limited proton mobility, and with increased combined losses observed for phosphothreonine compared with phosphoserine-containing peptides. The combined loss pathway was found to be less dominant under ion activation conditions associated with HCD-MS/MS. Finally, the contribution of carboxylic acid functional groups and backbone amide bonds to the water loss in the combined loss fragmentation pathway was determined via methyl esterification and by examination of a phosphopeptide lacking side-chain hydroxyl groups.
- Published
- 2013
16. Rational Design of a Colorimetric pH Sensor from a Soluble Retinoic Acid Chaperone
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James H. Geiger, Tetyana Berbasova, Babak Borhan, Meisam Nosrati, Ipek Yapici, Chrysoula Vasileiou, Kin Sing Stephen Lee, and Wenjing Wang
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Models, Molecular ,Receptors, Retinoic Acid ,Stereochemistry ,Molecular Conformation ,Retinoic acid ,Protonation ,Crystallography, X-Ray ,Protein Engineering ,Biochemistry ,Article ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Humans ,Schiff base ,biology ,Rational design ,Iminium ,Retinal ,General Chemistry ,Hydrogen-Ion Concentration ,chemistry ,Chaperone (protein) ,Mutation ,biology.protein ,Colorimetry ,Protein Binding ,Visible spectrum - Abstract
Reengineering of cellular retinoic acid binding protein II (CRABPII) to be capable of binding retinal as a protonated Schiff base is described. Through rational alterations of the binding pocket, electrostatic perturbations of the embedded retinylidene chromophore that favor delocalization of the iminium charge lead to exquisite control in the regulation of chromophoric absorption properties, spanning the visible spectrum (474-640 nm). The pKa of the retinylidene protonated Schiff base was modulated from 2.4 to 8.1, giving rise to a set of proteins of varying colors and pH sensitivities. These proteins were used to demonstrate a concentration-independent, ratiometric pH sensor.
- Published
- 2013
17. Kinetic Resolution of Unsaturated Amides in a Chlorocyclization Reaction: Concomitant Enantiomer Differentiation and Face Selective Alkene Chlorination by a Single Catalyst
- Author
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Richard J. Staples, Babak Borhan, and Arvind Jaganathan
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chemistry.chemical_classification ,Olefin fiber ,Halogenation ,Chemistry ,Alkene ,Stereoisomerism ,General Chemistry ,Alkenes ,Amides ,Biochemistry ,Catalysis ,Kinetic resolution ,Kinetics ,Colloid and Surface Chemistry ,Cyclization ,Organic chemistry ,Lewis acids and bases ,Enantiomer ,Chirality (chemistry) ,Selectivity - Abstract
The first example of a kinetic resolution via chlorofunctionalization of olefins is reported. The enantiomers of racemic unsaturated amides were found to have different hydrogen-bonding affinities for chiral Lewis bases in numerous solvents. This interaction was exploited in developing a kinetic resolution of racemic unsaturated amides via halocyclization. The same catalyst serves to both "sense chirality" in the substrate as well as mediate a highly face-selective chlorine delivery onto the olefin functionality, resulting in stereotriad products in up to 99:1 dr and up to 98.5:1.5 er. The selectivity factors were typically greater than 50 to allow for the simultaneous synthesis of both the products and unreacted substrates in highly enantioenriched form at yields approaching 50%. The reaction employs catalytic amounts (≤0.50 mol %) of a commercially available and recyclable organocatalyst.
- Published
- 2013
18. 3,4-Dihydroxypyrrolidines via Modified Tandem Aza-Payne/Hydroamination Pathway
- Author
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Babak Borhan, Nastaran Salehi Marzijarani, Richard J. Staples, Kumar Dilip Ashtekar, and Aman Kulshrestha
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Aza Compounds ,Pyrrolidines ,Lactams ,Molecular Structure ,Organic Chemistry ,Aziridine ,Ring (chemistry) ,Biochemistry ,Combinatorial chemistry ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Intramolecular force ,Alkoxide ,Electrophile ,Organic chemistry ,Hydroamination ,Physical and Theoretical Chemistry ,Amination - Abstract
The outcome of a tandem aza-Payne/hydroamination reaction is modified via the use of a latent nucleophile. The latter initially serves as an electrophile to intercept the aziridine alkoxide and afterward turns into a nucleophile thereby performing the aziridine ring opening, out competing the intramolecular aza-Payne pathway. Subsequent hydroamination in the same pot provides N-Ts enamide carbonates, which can be easily converted into biologically significant 3,4-dihydroxylactams.
- Published
- 2012
19. Absolute Configuration for 1,n-Glycols: A Nonempirical Approach to Long-Range Stereochemical Determination
- Author
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Richard J. Staples, Carmin E. Burrell, Xiaoyong Li, and Babak Borhan
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Models, Molecular ,Circular dichroism ,Porphyrins ,Chemistry ,Stereochemistry ,Circular Dichroism ,Diol ,Absolute configuration ,Stereoisomerism ,General Chemistry ,Crystallography, X-Ray ,Biochemistry ,Porphyrin ,Catalysis ,Glycols ,Crystallography ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Organometallic Compounds ,Molecule ,Derivatization ,Group 2 organometallic chemistry - Abstract
The absolute configurations of 1,n-glycols (n = 2-12, 16) bearing two chiral centers were rapidly determined via exciton-coupled circular dichroism (ECCD) using a tris(pentafluorophenyl)porphyrin (TPFP porphyrin) tweezer system in a nonempirical fashion devoid of chemical derivatization. A unique "side-on" approach of the porphyrin tweezer relative to the diol guest molecule is suggested as the mode of complexation.
- Published
- 2012
20. On the Chlorenium Source in the Asymmetric Chlorolactonization Reaction
- Author
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Janet M. Mueller, Babak Borhan, Richard J. Staples, Roozbeh Yousefi, and Daniel C. Whitehead
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Stereochemistry ,Chemistry ,Organic Chemistry ,Chlorine atom ,Activator (phosphor) ,polycyclic compounds ,Chlorine ,chemistry.chemical_element ,Physical and Theoretical Chemistry ,Biochemistry ,Combinatorial chemistry ,Catalysis - Abstract
N-Acylated N-chlorohydantoins are shown to be competent chlorenium sources in the (DHQD)(2)PHAL-mediated asymmetric chlorolactonization. The derivatives demonstrate the exact role of the N1 and N3 chlorine atoms in the parent dichlorohydantoins with the N1 chlorine serving as an inductive activator and the N3 chlorine being delivered to the substrate. The putative associated catalyst/chlorine source complex was experimentally demonstrated through a series of matched/mismatched experiments employing chiral N-chlorinated hydantoins.
- Published
- 2011
21. ‘Fixed charge’ chemical derivatization and data dependant multistage tandem mass spectrometry for mapping protein surface residue accessibility
- Author
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Wenjing Wang, Xiao Zhou, Babak Borhan, Yali Lu, and Gavin E. Reid
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Models, Molecular ,Receptors, Retinoic Acid ,Surface Properties ,Population ,Succinimides ,Peptide ,010402 general chemistry ,Mass spectrometry ,Tandem mass spectrometry ,Peptide Mapping ,01 natural sciences ,Residue (chemistry) ,Tandem Mass Spectrometry ,Structural Biology ,Humans ,education ,Peptide sequence ,Spectroscopy ,chemistry.chemical_classification ,education.field_of_study ,Chromatography ,Chemistry ,010401 analytical chemistry ,Peptide sequence tag ,Combinatorial chemistry ,0104 chemical sciences ,Indicators and Reagents ,Protein folding - Abstract
Protein surface accessible residues play an important role in protein folding, protein-protein interactions and protein-ligand binding. However, a common problem associated with the use of selective chemical labeling methods for mapping protein solvent accessible residues is that when a complicated peptide mixture resulting from a large protein or protein complex is analyzed, the modified peptides may be difficult to identify and characterize amongst the largely unmodified peptide population (i.e., the 'needle in a haystack' problem). To address this challenge, we describe here the development of a strategy involving the synthesis and application of a novel 'fixed charge' sulfonium ion containing lysine-specific protein modification reagent, S,S'-dimethylthiobutanoylhydroxysuccinimide ester (DMBNHS), coupled with capillary HPLC-ESI-MS, automated CID-MS/MS, and data-dependant neutral loss mode MS(3) in an ion trap mass spectrometer, to map the surface accessible lysine residues in a small model protein, cellular retinoic acid binding protein II (CRABP II). After reaction with different reagent:protein ratios and digestion with Glu-C, modified peptides are selectively identified and the number of modifications within each peptide are determined by CID-MS/MS, via the exclusive neutral loss(es) of dimethylsulfide, independently of the amino acid composition and precursor ion charge state (i.e., proton mobility) of the peptide. The observation of these characteristic neutral losses are then used to automatically 'trigger' the acquisition of an MS(3) spectrum to allow the peptide sequence and the site(s) of modification to be characterized. Using this approach, the experimentally determined relative solvent accessibilities of the lysine residues were found to show good agreement with the known solution structure of CRABP II.
- Published
- 2010
22. Fluorinated Porphyrin Tweezer: A Powerful Reporter of Absolute Configuration forerythroandthreoDiols, Amino Alcohols, and Diamines
- Author
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Chrysoula Vasileiou, Babak Borhan, Xiaoyong Li, and Marina Tanasova
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Models, Molecular ,Steric effects ,Molecular Structure ,Metalloporphyrins ,Stereochemistry ,Static Electricity ,Supramolecular chemistry ,Absolute configuration ,Diastereomer ,Stereoisomerism ,General Chemistry ,Diamines ,Ring (chemistry) ,Amino Alcohols ,Binding, Competitive ,Biochemistry ,Porphyrin ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Alcohols ,Chirality (chemistry) - Abstract
A general and sensitive nonempirical protocol to determine the absolute configurations of erythro and threo diols, amino alcohols, and diamines is reported. Binding of diols to the porphyrin tweezer system is greatly enhanced by increasing the Lewis acidity of the metalloporphyrin. Supramolecular complexes formed between the porphyrin tweezer host and chiral substrates exhibited exciton-coupled bisignate CD spectra with predictable signs based on the substituents on the chiral center. The working model suggests that the observed helicity of the porphyrin tweezer is dictated via steric differentiation experienced by the porphyrin ring bound to each chiral center. A variety of erythro and threo substrates were investigated to verify this chiroptical method. Their absolute configurations were unequivocally determined, and thus a general mnemonic is provided for the assignment of chirality.
- Published
- 2008
23. Synthesis of the Proposed Structure of Mucoxin via Regio- and Stereoselective Tetrahydrofuran Ring-Forming Strategies
- Author
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Babak Borhan and Radha S. Narayan
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Rollinia ,Acetogenins ,Molecular Structure ,biology ,Chemistry ,Stereochemistry ,Spectrum Analysis ,Organic Chemistry ,Enantioselective synthesis ,Diastereomer ,Total synthesis ,Antineoplastic Agents ,Stereoisomerism ,biology.organism_classification ,Ring (chemistry) ,Chemical synthesis ,Lactones ,chemistry.chemical_compound ,Cyclization ,Acetogenin ,Fatty Alcohols ,Furans ,Tetrahydrofuran - Abstract
An enantioselective total synthesis of the proposed structure of mucoxin (1) is described. Mucoxin, an annonaceous acetogenin isolated from bioactive leaf extracts of Rollinia mucosa, is the first acetogenin containing a hydroxylated trisubstituted tetrahydrofuran (THF) ring. This natural product is a highly potent and specific antitumor agent against MCF-7 (breast carcinoma) cell lines (ED50 = 3.7 x 10(-3) microg/mL compared to adriamycin, ED50 = 1.0 x 10(-2) microg/mL). The total synthesis described herein features two regio- and stereoselective THF ring-forming reactions. The 2,3,5-trisubstituted THF portion (C13-C17) was accessed using a highly regioselective cyclization of a methylene-interrupted epoxydiol, and the 2,5-disubstituted THF ring (C8-C12) was conveniently assembled via a 1,2-n-triol cyclization strategy. The spectral data of the synthetic material and two of its diastereomers did not match the reported data for the natural product. On the basis of detailed spectroscopic analysis of the synthesized molecule, we reason that the spectral discrepancies are due to stereochemical misassignment of the natural product.
- Published
- 2006
24. Direct Oxidative Cleavage of α- and β-Dicarbonyls and α-Hydroxyketones to Diesters with KHSO5
- Author
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Jun Yan, Benjamin R. Travis, and Babak Borhan
- Subjects
Chemistry ,Reagent ,Cleave ,Organic Chemistry ,Organic chemistry ,Oxidative cleavage - Abstract
Presented is a methodology to oxidatively cleave α-hydroxyketones and α- or β-diones using the environmentally benign reagent KHSO5, prepared easily from Oxone, to diesters in one simple transformation. In addition, we undertook a mechanistic study to provide a plausible mechanistic interpretation. These reactions may prove to be valuable alternatives to other related metal-mediated processes.
- Published
- 2004
25. Facile Oxidation of Aldehydes to Acids and Esters with Oxone
- Author
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Meenakshi Sivakumar, G. Olatunji Hollist, Benjamin R. Travis, and Babak Borhan
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Chemistry ,Alcohol oxidation ,Organic Chemistry ,Organic chemistry ,General Medicine ,Physical and Theoretical Chemistry ,Biochemistry - Abstract
[reaction: see text] A highly efficient, mild, and simple protocol is presented for the oxidation of aldehydes to carboxylic acids utilizing Oxone as the sole oxidant. Direct conversion of aldehydes in alcoholic solvents to their corresponding ester products is also reported. These reactions may prove to be valuable alternatives to traditional metal-mediated oxidations.
- Published
- 2003
26. An Organocatalytic Asymmetric Chlorolactonization
- Author
-
Arvind Jaganathan, Roozbeh Yousefi, Daniel C. Whitehead, and Babak Borhan
- Subjects
Chromatography ,Chemistry ,Hydantoins ,Enantioselective synthesis ,Stereoisomerism ,General Chemistry ,Biochemistry ,Combinatorial chemistry ,Article ,Catalysis ,Fatty Acids, Monounsaturated ,Lactones ,Colloid and Surface Chemistry ,Cyclization ,Reagent ,Hydrocarbons, Chlorinated - Abstract
A reagent controlled organocatalytic enantioselective chlorolactonization reaction has been developed. Several 4-aryl pentenoic acids were cyclized in the presence of 0.1 equiv of (DHQD)(2)PHAL, employing various N-chlorinated hydantoins as the terminal chlorenium source. Ten examples are presented with selectivities ranging from 43 to 90% ee. This work represents the first example of an enantioselective reagent-controlled chlorolactonization that approaches synthetically useful enantioselectivities.
- Published
- 2010
27. Suspension Copolymerization as a Route to Trityl-Functionalized Polystyrene Polymers
- Author
-
Daniel M. Kurth, Jennifer A. Wilson, Matthew J. Gasch, Babak Borhan, Ying Ko, and Mark J. Kurth
- Subjects
chemistry.chemical_classification ,Chemical engineering ,Chemistry ,Organic Chemistry ,Copolymer ,Suspension polymerization ,Polymer ,Functionalized polystyrene ,Suspension (vehicle) - Published
- 1995
28. An Efficient Preparation of 18O-Labeled Epoxides
- Author
-
Emily M. Stocking, Mark J. Kurth, Bruce D. Hammock, Saman Nazarian, and Babak Borhan
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,1,8-Diazabicyclo[5.4.0]undec-7-ene ,chemistry ,Alkene ,Organic Chemistry ,Organic chemistry ,chemistry.chemical_element ,Iodine ,Dichloromethane - Published
- 1994
29. Total Synthesis of Haterumalides NA and NC via a Chromium-Mediated Macrocyclization
- Author
-
Jennifer M. Schomaker and Babak Borhan
- Subjects
Chromium ,Stereochemistry ,chemistry.chemical_element ,Stereoisomerism ,Biochemistry ,Medicinal chemistry ,Aldehyde ,Article ,Catalysis ,Colloid and Surface Chemistry ,Organometallic Compounds ,Animals ,Carbenoid ,Deoxygenation ,Group 2 organometallic chemistry ,chemistry.chemical_classification ,Aldehydes ,Chemistry ,Total synthesis ,General Chemistry ,Ethylenes ,Porifera ,Oxygen ,Cyclization ,Macrolides - Abstract
The syntheses of haterumalides NA and NC were accomplished via the macrocyclization of a chlorovinylidene chromium carbenoid onto a pendant aldehyde to generate the C8-C9 bond with the desired stereoisomer as the major product. Utilizing the latter chemistry enables access to both C9 hydroxylated (haterumalides NC and ND) and C9 deoxygenated forms (haterumalides NA, NB, and NE; via deoxygenation of the C9-hydroxyl).
- Published
- 2008
30. Engineering a Rhodopsin Protein Mimic
- Author
-
James H. Geiger, Babak Borhan, Montserrat Rabago-Smith, Chrysoula Vasileiou, and Rachael M. Crist
- Subjects
Rhodopsin ,genetic structures ,Receptors, Retinoic Acid ,Fluorescence spectrometry ,Retinoic acid ,Photoprotein ,Tretinoin ,Crystallography, X-Ray ,Protein Engineering ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Biomimetic Materials ,Humans ,Receptor ,Binding Sites ,biology ,Chemistry ,Lysine ,Binding protein ,Retinal ,General Chemistry ,Transmembrane protein ,Kinetics ,Spectrometry, Fluorescence ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,biology.protein ,Thermodynamics ,Spectrophotometry, Ultraviolet ,sense organs - Abstract
Due to the difficulties in handling and manipulating membrane-bound proteins, such as rhodopsin, and the lack of crystallographic information on the cone opsins, we have opted to engineer a protein mimic of the transmembrane G-protein coupled receptor. Human cellular retinoic acid binding protein (CRABPII), a well studied and characterized protein, has been reengineered into a protein that now will bind retinal as a protonated Schiff base with high binding affinity (Kd = 2 nM) mimicking that of rhodopsin.
- Published
- 2006
31. Osmium Tetroxide-Promoted Catalytic Oxidative Cleavage of Olefins: An Organometallic Ozonolysis
- Author
-
Radha S. Narayan, Benjamin R. Travis, and Babak Borhan
- Subjects
chemistry.chemical_classification ,Ozonolysis ,Alkene ,Osmium oxide ,General Chemistry ,Potassium peroxymonosulfate ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Osmium tetroxide ,chemistry ,Organic chemistry ,Organic synthesis ,Cycloalkene - Abstract
A mild, organometallic alternative to ozonolysis utilizing oxone and OsO(4) is presented. This is a direct oxidation of olefins via the carbon-carbon cleavage of an osmate ester by the action of oxone. Twenty-four different olefins were converted to their corresponding ketones or carboxylic acids in high yields (80%). Free alcohols, acetate- and benzyl-protected alcohols, and 1,2-diols were stable under these conditions. This method should be applicable for traditional organic synthesis.
- Published
- 2002
32. Zinc Porphyrin Tweezer in Host−Guest Complexation: Determination of Absolute Configurations of Diamines, Amino Acids, and Amino Alcohols by Circular Dichroism
- Author
-
Xuefei Huang, Koji Nakanishi, Babak Borhan, Nina Berova, and Barry H. Rickman
- Subjects
chemistry.chemical_classification ,Zinc porphyrin ,Circular dichroism ,Colloid and Surface Chemistry ,Chemistry ,Stereochemistry ,General Chemistry ,Biochemistry ,Catalysis ,Amino acid - Published
- 1998
33. Chemoenzymatic Synthesis of 11-cis-Retinal Photoaffinity Analog by Use of Squid Retinochrome
- Author
-
Roxanne Kunz, Koji Nakanishi, Babak Borhan, Kazuo Yoshihara, Andrew Y. Wang, and Nina Bojkova
- Subjects
11-cis retinal ,Squid ,Colloid and Surface Chemistry ,Retinochrome ,biology ,Chemistry ,Stereochemistry ,biology.animal ,General Chemistry ,Biochemistry ,Catalysis - Published
- 1997
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