DOCSLIB.ORG

Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Ba

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Ba University of Tennessee, Knoxville Trace: Tennessee Research and Creative Exchange Masters Theses Graduate School 12-2009 Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Based Lipid Probesto Investigate Lipid-Protein Binding Interactions Manpreet Kaur Cheema University of Tennessee - Knoxville Recommended Citation Cheema, Manpreet Kaur, "Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Based Lipid Probesto Investigate Lipid-Protein Binding Interactions. " Master's Thesis, University of Tennessee, 2009. https://trace.tennessee.edu/utk_gradthes/517 This Thesis is brought to you for free and open access by the Graduate School at Trace: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Masters Theses by an authorized administrator of Trace: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a thesis written by Manpreet Kaur Cheema entitled "Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Based Lipid Probesto Investigate Lipid-Protein Binding Interactions." I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Master of Science, with a major in Chemistry. Michael Best, Major Professor We have read this thesis and recommend its acceptance: David Baker, Frank Vogt Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official student records.) To the Graduate Council: I am submitting herewith a thesis written by Manpreet Kaur Cheema entitled “Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Based Lipid Probes to Investigate Lipid ‒Protein Binding Interactions.” I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Master of Science, with a major in Chemistry. Michael Best Major Professor We have read this thesis and recommend its acceptance: David Baker Frank Vogt ` Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduat e School (Original signatures are on the file with official student record) Design and Synthesis of FRET-Based Boronic Acid Receptors to Detect Carbohydrate Clustering and Development of Diacylglycerol-Based Lipid Probes to Investigate Lipid-Protein Binding Interactions A Thesis Presented for The Master of Science Degree University of Tennessee, Knoxville Manpreet Kaur Cheema December 2009 Acknowledgements First of all, I would like to thank my parents, without whose guidance and perseverance, I would not have been able to reach this stage in my life. Thank you, Dr. Best, for being a constant source of motivation and inspiration throughout the course of this degree. The things that I have learned as a graduate student in your research lab have helped me develop into a more confident chemist. I also want to take pleasure in thanking my group members for constantly being there for me and helping me get through tough times. I will really cherish the good times that we shared in this lab. I would like to take an opportunity to thank Irene Abia (Baker’s group) for synthesizing an important molecule for our research design. I also want to thank my family members for providing me all the moral support whenever I needed it the most. Thank you Mandy for making me have faith in me. Last but not the least; I would like to thank my friends, Simi, Shibani and Ashutosh for being my pillars of support during my stay here. You guys are like my family away from home. ii Abstract Carbohydrate–protein interactions play vital roles in various biochemical processes such as signal transduction and cell surface recognition events. The clustering of carbohydrates into dense domains such as lipid rafts regulates recognition by multivalent receptors (i.e. lectins). These regions are known to play important roles in biological processes such as cellular transduction and trafficking. In order to characterize the clustering of glycans on cell surfaces, detection of domains with high carbohydrate density is of great interest. In this thesis, we present the work based on a modular strategy to design and synthesize boronic acid-based carbohydrate receptors, which are termed as boronolectins because of their similarly in functions with lectins, in order to understand the molecular basis of carbohydrate–protein interactions. These receptors will then be employed for binding studies with carbohydrate based guests and catechol derivatized diol target molecules in order to study the binding interactions between the boronic acid receptors and diol moieties present in guest molecules. A second project that is described in this thesis is based on developing diacylglycerol-based lipid probes, which could be employed for studying protein ‒lipid binding interactions. Due to involvement of protein ‒lipid binding interactions in the onset of various pathophysiological conditions, it is of paramount importance to investigate these interactions at the molecular level. DAG (diacylglycerol) represents an important class of signaling lipids and members of the Protein kinase C (PKC) family are described as the main iii responsive receptors of DAG. PKCs are known to be involved in tumorigenesis. In order to elucidate the exact correlation between PKC activity and carcinogenesis, it will be beneficial to design and synthesize DAG-based lipid analogs. In this thesis, hence, a modular strategy to design and synthesize a class of DAG-based lipid analogs by appending reporter groups such as polyaromatic fluorophores in the sn -1 acyl chains via the traceless Staudinger ligation is described. In both the projects, the synthetic strategy adopted is based on a modular design in order to generate a common scaffold which undergoes modification at the last step to generate a class of fluorophore tagged analogs to be employed for studies. iv Table of Contents Chapter Page Chapter 1: Design, Synthesis and Binding studies of Boronic Acid Based Carbohydrate Sensors Background and significance ................................................................................1 Significance of carbohydrates in biological processes..........................................1 Boronic acids as receptor/lectin mimics................................................................4 Research design of boronic acid-based receptors..............................................12 FRET-based detection........................................................................................12 Design and synthesis of fluorophore tagged boronic acid sensors .....................15 Design and synthesis of divalent carbohydrate guest.........................................25 Binding studies....................................................................................................30 Experimental.......................................................................................................35 Chapter 2: Design and Synthesis of Azide-Labeled Diacylglycerol Analogs Background and significance .............................................................................53 Modular design of lipid probes ............................................................................57 Modular approach to synthesize fluorophore tagged lipid analogs .....................65 Experimental.......................................................................................................74 Appendix References .........................................................................................................90 NMR spectra.......................................................................................................96 Vita....................................................................................................................109 v List of Figures Figure Page Figure 1.1 Carbohydrate recognition by lectins, toxins, viruses etc. 3 Figure 1.2 Illustration of interaction between boronic acid and saccharide 5 Figure 1.3 Formation of reversible covalent linkages to diols by boronic acids 6 Figure 1.4 The binding process between phenylboronic acid and a diol 7 Figure 1.5 Examples of monovalent and bivalent boronic acid receptors 8 Figure 1.6 PET-derivatized boronic acid-based receptors 9 Figure 1.7 Various pyrene-appended boronic acid sensors 10 Figure 1.8 Examples of various types of boronic acid sensors 11 Figure 1.9 Diagrammmatic representation of boronic acid FRET pairs employed for carbohydrate recognition 13 Figure 1.10 FRET- conceptual description 15 Figure 1.11 Synthesis of pyrene-tagged boronic acid receptor 17 Figure 1.12 Alternate synthesis of pyrene-tagged protected boronic acid 18 Figure 1.13 Synthetic schemes for synthesis of FRET-dervatized boronic acid-based receptors 19 Figure 1.14 Modular approach using click reaction 21 Figure 1.15 Alternate synthesis of fluorophore-tagged receptors using click reaction 22 Figure 1.16 Attempted approach to synthesize fluorophore-tagged receptors 23 Figure 1.17 Alternate coupling reaction approach 24 Figure 1.18 Diagrammatic representation of design of divalent guests 26
Load more

Recommended publications
  • 1 Structure, Properties, and Preparation of Boronic Acid Derivatives Overview of Their Reactions and Applications Dennis G
    j1 1 Structure, Properties, and Preparation of Boronic Acid Derivatives Overview of Their Reactions and Applications Dennis G. Hall 1.1 Introduction and Historical Background Structurally, boronic acids are trivalent boron-containing organic compounds that possess one carbon-based substituent (i.e., a CÀB bond) and two hydroxyl groups to fill the remaining valences on the boron atom (Figure 1.1). With only six valence electrons and a consequent deficiency of two electrons, the sp2-hybridized boron atom possesses a vacant p-orbital. This low-energy orbital is orthogonal to the three substituents, which are oriented in a trigonal planar geometry. Unlike carbox- ylic acids, their carbon analogues, boronic acids, are not found in nature. These abiotic compounds are derived synthetically from primary sources of boron such as boric acid, which is made by the acidification of borax with carbon dioxide. Borate esters, one of the key precursors of boronic acid derivatives, are made by simple dehydration of boric acid with alcohols. The first preparation and isolation of a boronic acid was reported by Frankland in 1860 [1]. By treating diethylzinc with triethylborate, the highly air-sensitive triethylborane was obtained, and its slow oxidation in ambient air eventually provided ethylboronic acid. Boronic acids are the products of a twofold oxidation of boranes. Their stability to atmospheric oxidation is considerably superior to that of borinic acids, which result from the first oxidation of boranes. The product of a third oxidation of boranes, boric acid, is a very stable and relatively benign compound to humans (Section 1.2.2.3). Their unique properties and reactivity as mild organic Lewis acids, coupled with their stability and ease of handling, are what make boronic acids a particularly attractive class of synthetic intermediates.
    [Show full text]
  • Synthesis and Improvement of Self-Healing Boronate Ester Hydrogels
    SYNTHESIS AND IMPROVEMENT OF SELF-HEALING BORONATE ESTER HYDROGELS By CHRISTOPHER CHI-LONG DENG A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2017 © 2017 Christopher Chi-long Deng To friends and family and loved ones departed ACKNOWLEDGMENTS Numerous people have supported me to this point. I would like to thank all of my previous teachers throughout my education for the foundation they gave to me and the valuable work that they do for all students. I thank Dr. Yi Zhang for allowing me to work in her lab and gain valuable experience. I would also like to thank Dr. Bill Dolbier for sharing his passion for organic chemistry and assisting me in entering graduate school. Of course, I am grateful towards Dr. Brent Sumerlin for accepting me in his group. His expectations and guidance have been valuable in my scientific growth. Also, I would like to thank my committee of Dr. Ken Wagener, Dr. Stephen Miller, Dr. Adam Veige, and Dr. Anthony Brennan. I appreciate the time taken from their busy schedules and their advice over the years. I would also like to acknowledge the University of Florida, the Department of Chemistry, and the Butler Polymer Laboratory for the opportunity to pursue my doctorate and providing a supportive environment for myself and all graduate students. I am grateful to the members of the Sumerlin group. I have the most interaction with them on a daily basis, and it has been a tremendous source of support both personally and professionally.
    [Show full text]
  • RSC Advances PAPER
    View Article Online / Journal Homepage / Table of Contents for this issue RSC Advances Dynamic Article Links Cite this: RSC Advances, 2012, 2, 3968–3977 www.rsc.org/advances PAPER Palladium nanoshells coated with self-assembled monolayers and their catalytic properties Jun-Hyun Kim,*a Joon-Seo Park,b Hae-Won Chung,c Brett W. Bootea and T. Randall Lee*c Received 13th October 2011, Accepted 6th February 2012 DOI: 10.1039/c2ra00883a This report describes the preparation and characterization of palladium nanoshells protected with alkanethiol self-assembled monolayers (SAMs) and their application as efficient catalysts. Monodispersed silica core particles (y100 nm in diameter) were prepared and coated with a thin layer of palladium (y20 nm in thickness). Subsequently, the palladium nanoshells were treated with two separate alkanethiol adsorbates having different alkyl chain lengths: dodecanethiol (C12SH) and hexadecanethiol (C16SH). The optical properties, morphology, and chemical structure/composition of these nanoshells were thoroughly examined by ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy. Additional studies revealed that these SAM-coated palladium nanoshells possessed enhanced colloidal stability in nonpolar solvents and in the solid state. Further, palladium nanoshells modified with C16SH SAM coatings were employed in the Suzuki coupling of phenylboronic acid with iodobenzene in organic solvents. Notably, these SAM-coated nanoshells afforded a greater conversion yield than that of related bare palladium nanoshells. Downloaded on 19 February 2013 Introduction palladium nanoparticles as catalysts depend largely on their size, shape, surrounding medium, and dispersion ability in organic The controlled fabrication of nanoscale metallic particles offers the solvents, which facilitates their manipulation and incorporation 1–5 opportunity to develop novel catalysts.
    [Show full text]
  • Electronic Supporting Information
    Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is © The Royal Society of Chemistry 2017 Electronic Supporting Information for Ratiometric Electrochemical Detection of Hydrogen Peroxide and Glucose by Sean Goggins,a* Ellen A. Apsey,a Mary F. Mahona and Christopher G. Frosta a Department of Chemistry, 1 South, University of Bath, Claverton Down, Bath, BA2 7AY, UK * Corresponding author: [email protected] Contents General Information ................................................................................................................................... S4 Instruments and Analysis ........................................................................................................................ S4 Materials ................................................................................................................................................. S4 Chemicals ................................................................................................................................................ S4 Electrochemistry ..................................................................................................................................... S5 Diagnostic Assays .................................................................................................................................... S5 Synthetic Routes ......................................................................................................................................... S6 Synthetic Route
    [Show full text]
  • Chemistry Research Report
    Contents 3 Welcome 5 Profiles 37 Publications 51 Staff and students 55 Student prizes & scholarships 58 Ruth Gall profile 60 Graduates of 2017 Front cover: Portrait of A/Prof. Ruth Gall (1923-2017), the first woman to Head the School of Chemistry at the University of Sydney, painted by local artist Dr Kate Gradwell. The School of Chemistry at the University of Sydney is one of the main centres for chemical research and education in Australia and has access to a comprehensive range of modern research and teaching facilities. The School attracts an outstanding cohort of undergraduate students including talented students from all states of Australia. It has a large cohort of both local and international postgraduate research students and offers a vibrant and world class research environment. GENERAL INFORMATION 3 WELCOME HEAD OF SCHOOL Professor Phil Gale at such conferences, reflecting both the excellence of the Head of School School of Chemistry research they are undertaking and their outstanding ability to present this to an audience. Highlights of the awards to staff and students in 2017 include the RJW Le Fèvre Memorial Prize to A/Prof Deanna D’Alessandro; Dr Ivan Kassal was the recipient of the Tall Poppy Award; A/Prof Liz New was a finalist in the 3M Eureka Prize for emerging leader in science; Prof Kate Jolliffe was awarded A.J. Birch Medal; Mr Phil Karpati was the global winner of the 2017 Undergraduate Awards - Phil was also awarded a 2017 Westpac Future Leaders scholarship; and the RACI Cornforth Medal for the best PhD thesis in Australia went to Ms Amandeep Kaur.
    [Show full text]
  • Diyl Bis(Phenyl-Methanone) Via Carbonylative Coupling
    Asian Journal of Chemistry; Vol. 25, No. 15 (2013), 8611-8613 http://dx.doi.org/10.14233/ajchem.2013.14863 Synthesis of Biphenyl- 4,4'-Diyl bis(phenyl-methanone) via Carbonylative Coupling 1,* 2 1,* DO-HUN LEE , JUNG-TAI HAHN and DAI-IL JUNG 1Department of Chemistry, Dong-A University, Busan 604 714, Republic of Korea 2Department of Beautycare, Youngdong University, Youngdong 370 701, Republic of Korea *Corresponding authors: Tel: +82 51 2007249; +82 51 2001053; E-mail: [email protected]; [email protected] (Received: 23 November 2012; Accepted: 26 August 2013) AJC-14008 Luminescent meterials have a major technological role for human kind in the form of application such as organic and inorganic light emitters for flat panel and flexible displays such as plasma displays, LCD displays and OLED displays. To develop a luminescent material with high colour purity, luminous efficiency and stability, we synthesized diketone by carbonylative Suzuki coupling in the presence of Pd(NHC) (NHC = N-heterocyclic carbene) complex as the catalyst. Carbonylative coupling of 4,42-diiodobiphenyl and phenylboronic acid was investigated to study in detail the catalytic ability of the Pd(NHC) complex. Reactions were carried out using both CO and metal carbonyls. Bis-(1,3-dihydro-1,3-dimethyl-2H-imidazol-2-ylidene) diiodo palladium was used as the catalytic complex. Reaction products biphenyl-4,4'-diyl bis(phenyl methanone) 3 and (4'-iodobiphenyl-4-yl)(phenyl)methanone 4 were obtained as a result of CO insertion into the palladium(II)-aryl bond. However, when pyridine-4-yl boronic acid was used in place of phenylboronic acid as the starting reagent, synthetic reaction yielding 3 and 4 were found not to occur.
    [Show full text]
  • Supporting Information for Boronic Acid–DMAPO Cooperative Catalysis for Dehydrative Condensation Between Carboxylic Acids and Amines
    Electronic Supplementary Material (ESI) for Chemical Science. This journal is © The Royal Society of Chemistry 2015 Supporting Information for Boronic Acid–DMAPO Cooperative Catalysis for Dehydrative Condensation between Carboxylic Acids and Amines Kazuaki Ishihara*†‡ and Yanhui Lu† †Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan ‡Japan Science and Technology (JST), CREST, Japan E-mail: [email protected] Contents General Methods……………………………………………………………….….……..……S2 Detailed Synthetic Procedures and Characterization of the Products…………….….…....S2 Inert Species 9…………………..………………………………….………………………....S11 Control Experiments for the Chemoselective Dehydrative Condensation of Unsaturated Carboxylic Acids………………………………………………….…....S15 References…………………………………………………………………………………….S17 1H and 13C NMR Charts of New Compounds……………………………………….……..S18 S1 Experimental section General Methods. IR spectra were recorded on a JASCO FT/IR-460 plus spectrometer. 1H NMR spectra were measured on a JEOL ECS-400 spectrometer (400 MHz) at ambient temperature. Data were recorded as follows: chemical shift in ppm from internal tetramethysilane on the δ scale, multiplicity (s = singlet; d = doublet; t = triplet; m = multiplet), coupling constant (Hz), and integration. 13C NMR spectra were measured on a JEOL ECS-400 (100 MHz). Chemical shifts were recorded in ppm from the solvent resonance employed as the internal standard (CDCl3 at 77.0 11 ppm). B NMR spectra were taken on a JEOL ECS-400 (128 MHz) spectrometer using B(OMe)3 as an external reference. Analytical HPLC was performed on a Shimadzu Model LC-10AD instrument coupled diode array-detector SPD-MA-10A-VP using a column of Daicel CHIRALCEL OD-H (4.6 # 250 mm). Optical rotations were measured on a RUDOLPH AUTOPOL IV digital polarimeter.
    [Show full text]
  • Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Heterocyclic Acceptors
    NIH Public Access Author Manuscript Chemistry. Author manuscript; available in PMC 2014 January 02. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Chemistry. 2013 January 2; 19(1): 74–77. doi:10.1002/chem.201203643. Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Heterocyclic Acceptors Jeffrey C. Holder#, Dr. Alexander N. Marziale#, Dr. Michele Gatti, Bin Mao, and Prof. Brian M. Stoltz Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E California Blvd, MC 101-20, Pasadena, CA 91125 (USA) Keywords Heterocycles; Conjugate Addition; Asymmetric Catalysis; Palladium; Arylboronic Acids Palladium-catalyzed asymmetric conjugate additions are an increasingly versatile class of enantioselective reactions that allow for stereoselective alkylation and arylation of α,β- unsaturated conjugate acceptors.[1] These processes often utilize easily-handled, air- and water-stable boron nucleophiles that render these reactions highly tolerant of oxygen and moisture.[2] Recently, our group disclosed the asymmetric conjugate addition of arylboronic acids to cyclic enones facilitated by a palladium catalyst derived in situ from palladium(II) trifluoroacetate and a chiral pyridinooxazoline (PyOX) ligand (5).[3] Notably, our catalyst system was generally applicable for 5-, 6-, and 7-membered carbocyclic enones. The numerous advantages of this system encouraged us to seek application to heterocyclic molecules, in order to demonstrate the broad utility of this reaction for the synthesis of pharmaceutically relevant molecules. Herein, we report the first general enantioselective conjugate addition of arylboronic acids to heterocyclic conjugate acceptors derived from chromones and 4-quinolones utilizing the Pd/PyOX catalyst system.
    [Show full text]
  • Polymer Substrates for Fiber-Optic Chemical Sensors
    University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Winter 1992 Polymer substrates for fiber-optic chemical sensors Amy Elizabeth Straub University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Straub, Amy Elizabeth, "Polymer substrates for fiber-optic chemical sensors" (1992). Doctoral Dissertations. 1718. https://scholars.unh.edu/dissertation/1718 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps.
    [Show full text]
  • Applications of Boronic Acids in Organic Synthesis
    Applications of Boronic Acids in Organic Synthesis A dissertation presented by Pavel Starkov in partial fulfilment of the requirements for the award of the degree of DOCTOR OF PHILOSOPHY at UNIVERSITY COLLEGE LONDON Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street WC1H 0AJ London Declaration This dissertation is the result of my own work. Where information has been derived from other sources it has been clearly indicated so and acknowledged accordingly. /Pavel Starkov/ ii Abstract This thesis describes progress on the application of boronic acids and borate esters as catalysts and reagents in synthetic organic synthesis, focusing on two areas: one-pot enolate formation/aldol reactions and amide bond formation. Chapter 1 introduces the reader to boronic acids and derivatives thereof, their methods of preparation and their use in synthetic organic chemistry as reactants, reagents and catalysts. Chapter 2 covers current chemical methods and cellular alternatives for amide bond formation. Here, we also discuss our use of boron reagents for the activation of carboxylic acids as well as amides. Chapter 3 introduces a new concept in catalytic aldol reactions, i.e. an alternative strategy to access boron enolates in situ. The work covers successful demonstration of the feasibility of such an approach on an intramolecular system. A novel variation of aerobic Chan–Evans– Lam coupling, an intramolecular coupling of an aliphatic alcohol with a boronic acid using catalytic copper, is also introduced Chapter 4 builds on our observations on gold catalysis and especially that in relation to electrophilic halogenations. Chapter 5 contains full details of the experimental procedures.
    [Show full text]
  • 1 Rhodium- and Palladium-Catalyzed Asymmetric Conjugate Additions Guillaume Berthon and Tamio Hayashi
    1 1 Rhodium- and Palladium-Catalyzed Asymmetric Conjugate Additions Guillaume Berthon and Tamio Hayashi 1.1 Introduction Since the seminal report by Uemura [1] in 1995 for palladium, and by Miyaura in 1997 for rhodium [2], the late transition metal-catalyzed conjugate addition of organoboron reagents to activated alkenes has emerged as one of the most functional group-tolerant and reliable carbon–carbon bond-forming processes. The maturity of this methodology is such that it has become an ideal testing ground for new ligand concepts and design, as will be illustrated throughout this chapter. A true statement to the robustness of this process is the application of Rh-catalyzed enantioselective conjugate addition (ECA) on a kilogram-scale for the manufacture of advanced pharmaceutical ingredients, and its use as a key step in the synthesis of complex natural products [3–5]. In this chapter, an overview will be provided – spanning from 2003 to mid-2009 – of the developments in the field of rhodium- and palladium-catalyzed ECA of organometallic reagents (B, Si, Zn, and Ti) to activated alkenes. The chapter is not intended to be comprehensive, and will include only selected examples of this powerful methodology. For more in-depth and comprehensive accounts, the reader should consult a number of excellent reviews that are available on this subject [6–16]. 1.2 Rh-Catalyzed ECA of Organoboron Reagents This section will include details of the state of the art for the rhodium-catalyzed ECA of organoboron reagents to activated olefins. Special emphasis will be placed on α,β-unsaturated ketones, as this substrate class has attracted the most attention and undergone thorough investigation with a plethora of different ligand systems.
    [Show full text]
  • Suzuki-Miyaura Cross Coupling Reaction
    Please inquire for pricing and availability of listed products to our local sales representatives. 1 Suzuki-Miyaura Cross Coupling Reaction Biaryl compounds are utilized as important basic skeletons of functional materials such as liquid crystals and biologically active compounds. For example, the biphenyl skeleton of diflunisal demonstrates analgesic and anti-inflammatory effects, and 4-alkyl-4'-cyanobiphenyl is a liquid crystal material. Traditionally, the Ullmann reaction and the Gomberg- Bachmann-Hey reaction have been used for biaryl formation. However, the reaction selectivities and yields of the anticipated products were poor. In 1981, Suzuki and Miyaura et al. made a breakthough in the methodology of biaryl compound synthesis by using aryl boronic acids and aryl bromide under homogeneous palladium catalyzed conditions in the presence of bases (eq.1).1) The recent report made on the modification of the cross- coupling reaction was upon the usage of the amphiphilic polymer-supported Pd catalyst. This Pd catalyst forms a networked supermolecular complex, which is insoluble in water and in organic solvents, and it is easily recovered from the reaction system. As Pd is firmly supported by phosphino groups of the copolymer, it does not elute during the reaction, Under mild conditions, these reactions produce biaryl and therefore it can be used repeatedly (eq. 6).5) compounds with high selectivities and excellent yields. Moreover, there are few limitations in terms of functional group requirements, thus making it possible for the synthesis of biaryls with diverse components such as hydroxy, carboxyl and formyl groups, etc. (eq. 2). Furthermore, it is possible to synthesize sterically-hindered pyridylphenol derivatives (eq.
    [Show full text]