Retrosynthetic Analysis and Synthetic Planning
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Philosophy of Science and Philosophy of Chemistry
Philosophy of Science and Philosophy of Chemistry Jaap van Brakel Abstract: In this paper I assess the relation between philosophy of chemistry and (general) philosophy of science, focusing on those themes in the philoso- phy of chemistry that may bring about major revisions or extensions of cur- rent philosophy of science. Three themes can claim to make a unique contri- bution to philosophy of science: first, the variety of materials in the (natural and artificial) world; second, extending the world by making new stuff; and, third, specific features of the relations between chemistry and physics. Keywords : philosophy of science, philosophy of chemistry, interdiscourse relations, making stuff, variety of substances . 1. Introduction Chemistry is unique and distinguishes itself from all other sciences, with respect to three broad issues: • A (variety of) stuff perspective, requiring conceptual analysis of the notion of stuff or material (Sections 4 and 5). • A making stuff perspective: the transformation of stuff by chemical reaction or phase transition (Section 6). • The pivotal role of the relations between chemistry and physics in connection with the question how everything fits together (Section 7). All themes in the philosophy of chemistry can be classified in one of these three clusters or make contributions to general philosophy of science that, as yet , are not particularly different from similar contributions from other sci- ences (Section 3). I do not exclude the possibility of there being more than three clusters of philosophical issues unique to philosophy of chemistry, but I am not aware of any as yet. Moreover, highlighting the issues discussed in Sections 5-7 does not mean that issues reviewed in Section 3 are less im- portant in revising the philosophy of science. -
Peptide Chemistry up to Its Present State
Appendix In this Appendix biographical sketches are compiled of many scientists who have made notable contributions to the development of peptide chemistry up to its present state. We have tried to consider names mainly connected with important events during the earlier periods of peptide history, but could not include all authors mentioned in the text of this book. This is particularly true for the more recent decades when the number of peptide chemists and biologists increased to such an extent that their enumeration would have gone beyond the scope of this Appendix. 250 Appendix Plate 8. Emil Abderhalden (1877-1950), Photo Plate 9. S. Akabori Leopoldina, Halle J Plate 10. Ernst Bayer Plate 11. Karel Blaha (1926-1988) Appendix 251 Plate 12. Max Brenner Plate 13. Hans Brockmann (1903-1988) Plate 14. Victor Bruckner (1900- 1980) Plate 15. Pehr V. Edman (1916- 1977) 252 Appendix Plate 16. Lyman C. Craig (1906-1974) Plate 17. Vittorio Erspamer Plate 18. Joseph S. Fruton, Biochemist and Historian Appendix 253 Plate 19. Rolf Geiger (1923-1988) Plate 20. Wolfgang Konig Plate 21. Dorothy Hodgkins Plate. 22. Franz Hofmeister (1850-1922), (Fischer, biograph. Lexikon) 254 Appendix Plate 23. The picture shows the late Professor 1.E. Jorpes (r.j and Professor V. Mutt during their favorite pastime in the archipelago on the Baltic near Stockholm Plate 24. Ephraim Katchalski (Katzir) Plate 25. Abraham Patchornik Appendix 255 Plate 26. P.G. Katsoyannis Plate 27. George W. Kenner (1922-1978) Plate 28. Edger Lederer (1908- 1988) Plate 29. Hennann Leuchs (1879-1945) 256 Appendix Plate 30. Choh Hao Li (1913-1987) Plate 31. -
Peptide Synthesis: Chemical Or Enzymatic
Electronic Journal of Biotechnology ISSN: 0717-3458 Vol.10 No.2, Issue of April 15, 2007 © 2007 by Pontificia Universidad Católica de Valparaíso -- Chile Received June 6, 2006 / Accepted November 28, 2006 DOI: 10.2225/vol10-issue2-fulltext-13 REVIEW ARTICLE Peptide synthesis: chemical or enzymatic Fanny Guzmán Instituto de Biología Pontificia Universidad Católica de Valparaíso Avenida Brasil 2950 Valparaíso, Chile Fax: 56 32 212746 E-mail: [email protected] Sonia Barberis Facultad de Química, Bioquímica y Farmacia Universidad Nacional de San Luis Ejército de los Andes 950 (5700) San Luis, Argentina E-mail: [email protected] Andrés Illanes* Escuela de Ingeniería Bioquímica Pontificia Universidad Católica de Valparaíso Avenida Brasil 2147 Fax: 56 32 2273803 E-mail: [email protected] Financial support: This work was done within the framework of Project CYTED IV.22 Industrial Application of Proteolytic Enzymes from Higher Plants. Keywords: enzymatic synthesis, peptides, proteases, solid-phase synthesis. Abbreviations: CD: circular dichroism CLEC: cross linked enzyme crystals DDC: double dimer constructs ESI: electrospray ionization HOBT: hydroxybenzotriazole HPLC: high performance liquid hromatography KCS: kinetically controlled synthesis MALDI: matrix-assisted laser desorption ionization MAP: multiple antigen peptide system MS: mass spectrometry NMR: nuclear magnetic resonance SPS: solution phase synthesis SPPS: solid-phase peptide synthesis t-Boc: tert-butoxycarbonyl TCS: thermodynamically controlled synthesis TFA: trifluoroacetic acid Peptides are molecules of paramount importance in the medium, biocatalyst and substrate engineering, and fields of health care and nutrition. Several technologies recent advances and challenges in the field are analyzed. for their production are now available, among which Even though chemical synthesis is the most mature chemical and enzymatic synthesis are especially technology for peptide synthesis, lack of specificity and relevant. -
M.Sc. Organic Chemistry
ST. JOSEPH’S COLLEGE (AUTONOMOUS) BENGALURU-27 DEPARTMENT OF CHEMISTRY SYLLABUS FOR POSTGRADUATE COURSE IN ORGANIC CHEMISTRY 2019-21 Re-accredited with ‘A++’ GRADE and 3.79/4 CGPA by NAAC Recognised as “College of Excellence” by UGC The Postgraduate programme in chemistry is designed to give students a good foundation in Chemistry and develop in them problem solving and experimental skills so that they are well prepared for further studies in specialized areas of Chemistry or for employment in academic institutions and in industry. Mission statement: To promote among our learners the skills of thinking, experimentation and application of the knowledge gained. To promote concern for environment and to develop appreciation for green Chemistry. To prepare our students for life in the larger community. Benchmark Statements for the Course: To instil in students a sense of enthusiasm for chemistry, an appreciation of its application in different contexts, and to involve them in intellectually stimulating and satisfying experience of learning and studying. To provide students with a broad and balanced foundation of chemical knowledge and practical skills. Teaching-Learning: Although the lecture method is extensively used, the students are also encouraged to do self- study through other activities like assignments, seminars, quiz, viva-voce etc. Co-curricular Activities: The Chemical Society for postgraduate (P.G.) students provides them with a platform to interact with students of other institutions and also with eminent scientists from -
Polyphenylene Dendrimers
Polyphenylene Dendrimers - Design and Synthesis of Monodisperse Functional Nanoparticles Dissertation zur Erlangung des Grades "Doktor der Wissenschaften" am Fachbereich Chemie und Pharmazie der Johannes Gutenberg-Universität in Mainz vorgelegt von Stefan Bernhardt geb. in Hofheim a. Ts. Mainz 2005 Dekan: Herr Prof. Dr. P. Langguth 1. Berichterstatter: 2. Berichterstatter: Tag der mündlichen Prüfung: 26.06.2006 Die vorliegende Arbeit wurde in der Zeit von März 2002 bis März 2005 am Max-Planck- Institut für Polymerforschung in Mainz unter Anleitung von Herrn Prof. Dr. K. Müllen durchgeführt. Dedicated to my wife If we knew what we were doing it wouldn't be research. Einstein, Albert Index of Abbreviations: AFM atomic force microscopy Anal. analysis calcd. calculated TBAF tetrabutylammoniumfluoride-hexahydrate CD2Cl2 deuterated methylenechloride δ chemical shift / ppm d doublet d8THF deuterated tetrahydrofuran DEE diethylether DMF dimethylformamide DMSO dimethylsulfoxide eq. equivalent EtOH ethanol FD field desorption G1, G2, G3, first-, second-, and third-dendrimer generation GS ground state h hours J coupling constant / Hz LE locally-excited state m multiplett m / g weight in gram MALDI-TOF matrix-assisted laser desorption/ionization-time of flight MCH methylcyclohexane MeOH methanol MS mass spectrometry n refractive index NMR nuclear magnetic resonance PE petroleum ether, low boiling PMI perylene monoimide PPh3 triphenylphosphine ppm parts per million (chemical shift in NMR spectroscopy) RT room temperature s singulet SM single molecule T temperature / °K or °C t triplet TCSPC time-correlated single photon counting TEA triethylamine THF tetrahydrofuran TIPS tri-iso-propylsilyl TPA triphenylamine UV ultraviolett Фflu fluorescence quantum yield τflu decay time of fluorescence kfwd and krev forward and reverse electron transfer rate constants CS charge-separated state Table of contents 1 INTRODUCTION................................................................................................ -
Enantioselective, Convergent Synthesis of the Ineleganolide Core by a Tandem Annulation Cite This: Chem
Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Enantioselective, convergent synthesis of the ineleganolide core by a tandem annulation Cite this: Chem. Sci.,2017,8,507 cascade† Robert A. Craig, II, Jennifer L. Roizen, Russell C. Smith, Amanda C. Jones, Scott C. Virgil and Brian M. Stoltz* An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is disclosed. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary ether and facilitate the synthesis of a 1,3-cis- cyclopentenediol building block. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation–Cope rearrangement cascade under unusually mild conditions. Computational evaluation of ground state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the Creative Commons Attribution 3.0 Unported Licence. investigation of the conformational rigidity of these highly constrained and compact polycyclic structures. This work represents the first successful synthesis of the core structure of any member of the furanobutenolide-derived polycyclic norcembranoid diterpene family of natural products. Advanced Received 28th July 2016 synthetic manipulations generated a series of natural product-like compounds that were shown to Accepted 15th August 2016 possess selective secretory antagonism of either interleukin-5 or interleukin-17. This bioactivity stands in DOI: 10.1039/c6sc03347d contrast to the known antileukemic activity of ineleganolide and suggests the norcembranoid natural www.rsc.org/chemicalscience product core may serve as a useful scaffold for the development of diverse therapeutics. This article is licensed under a Introduction this rigid polycyclic scaffold is decorated with a network of nine stereogenic centers, eight of which are contiguous. -
Synthesis and Biosynthesis of Polyketide Natural Products
Syracuse University SURFACE Chemistry - Dissertations College of Arts and Sciences 12-2011 Synthesis and Biosynthesis of Polyketide Natural Products Atahualpa Pinto Syracuse University Follow this and additional works at: https://surface.syr.edu/che_etd Part of the Chemistry Commons Recommended Citation Pinto, Atahualpa, "Synthesis and Biosynthesis of Polyketide Natural Products" (2011). Chemistry - Dissertations. 181. https://surface.syr.edu/che_etd/181 This Dissertation is brought to you for free and open access by the College of Arts and Sciences at SURFACE. It has been accepted for inclusion in Chemistry - Dissertations by an authorized administrator of SURFACE. For more information, please contact [email protected]. Abstract Traditionally separate disciplines of a large and broad chemical spectrum, synthetic organic chemistry and biochemistry have found in the last two decades a fertile common ground in the area pertaining to the biosynthesis of natural products. Both disciplines remain indispensable in providing unique solutions on numerous questions populating the field. Our contributions to this interdisciplinary pursuit have been confined to the biosynthesis of polyketides, a therapeutically and structurally diverse class of natural products, where we employed both synthetic chemistry and biochemical techniques to validate complex metabolic processes. One such example pertained to the uncertainty surrounding the regiochemistry of dehydration and cyclization in the biosynthetic pathway of the marine polyketide spiculoic acid A. The molecule's key intramolecular cyclization was proposed to occur through a linear chain containing an abnormally dehydrated polyene system. We synthesized a putative advanced polyketide intermediate and tested its viability to undergo a mild chemical transformation to spiculoic acid A. In addition, we applied a synthetic and biochemical approach to elucidate the biosynthetic details of thioesterase-catalyzed macrocyclizations in polyketide natural products. -
Lecture 1: Strategies and Tactics in Organic Synthesis
Massachusetts Institute of Technology Organic Chemistry 5.511 October 3, 2007 Prof. Rick L. Danheiser Lecture 1: Strategies and Tactics in Organic Synthesis Retrosynthetic Analysis The key to the design of efficient syntheses ". the grand thing is to be able to reason backwards. That is a very useful accomplishment, and a very easy "The end is where we start from...." one, but people do not practice it much." T. S. Eliot, in "The Four Quartets" Sherlock Holmes, in "A Study in Scarlet" Strategy Tactics overall plan to achieve the means by which plan ultimate synthetic target is implemented intellectual experimental retrosynthetic planning synthetic execution TRANSFORMS REACTIONS Target Precursor Precursor Target Definitions Retron Structural unit that signals the application of a particular strategy algorithm during retrosynthetic analysis. Transform Imaginary retrosynthetic operation transforming a target molecule into a precursor molecule in a manner such that bond(s) can be reformed (or cleaved) by known or reasonable synthetic reactions. Strategy Algorithm Step-by-step instructions for performing a retrosynthetic operation. "...even in the earliest stages of the process of simplification of a synthetic problem, the chemist must make use of a particular form of analysis which depends on the interplay between structural features that exist in the target molecule and the types of reactions or synthetic operations available from organic chemistry for the modification or assemblage of structural units. The synthetic chemist has learned by experience to recognize within a target molecule certain units which can be synthesized, modified, or joined by known or conceivable synthetic operations...it is convenient to have a term for such units; the term "synthon" is suggested. -
From Carbon-11-Labeled Amino Acids to Peptides in Positron Emission Tomography: the Synthesis and Clinical Application Aleksandra Pekošak, Ulrike Filp, Alex J
Mol Imaging Biol (2018) DOI: 10.1007/s11307-018-1163-5 * The Author(s), 2018. This article is an open access publication REVIEW ARTICLE From Carbon-11-Labeled Amino Acids to Peptides in Positron Emission Tomography: the Synthesis and Clinical Application Aleksandra Pekošak, Ulrike Filp, Alex J. Poot, Albert D. Windhorst Radionuclide Center, Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1085c, 1081 HV, Amsterdam, The Netherlands Abstract Radiolabeled amino acids, their derivatives and peptides have a broad scope of application and can be used as receptor ligands, as well as enzyme substrates for many different diseases as radiopharmaceutical tracers. Over the past few decades, the application of molecular imaging techniques such as positron emission tomography (PET) has gained considerable importance and significance in diagnosis in today’s advanced health care. Next to that, the availability of cyclotrons and state-of-the-art radiochemistry facilities has progressed the production of imaging agents enabling the preparation of many versatile PET radiotracers. Due to many favorable characteristics of radiolabeled amino acids and peptides, they can be used for tumor staging and monitoring the progress of therapy success, while aromatic amino acids can be employed as PET tracer to study neurological disorders. This review provides a comprehensive overview of radiosynthetic and enzymatic approaches towards carbon-11 amino acids, their analogues and peptides, with focus on stereoselective reactions, and reflects upon their clinical application. Key Words: Carbon-11, Amino acid, Peptide, Radiolabeling, PET imaging Introduction D-glucose ([18F]FDG) as well as a large variety of other PET tracers like receptor ligands or enzyme substrates. -
Convergent Synthesis of Thioether Containing Peptides
molecules Article Convergent Synthesis of Thioether Containing Peptides Spyridon Mourtas 1,2, Christina Katakalou 1, Dimitrios Gatos 1 and Kleomenis Barlos 1,3,* 1 Department of Chemistry, University of Patras, 26510 Rio Patras, Greece; [email protected] (S.M.); [email protected] (C.K.); [email protected] (D.G.) 2 Institute of Chemical Engineering Sciences of the Foundation for Research and Technology Hellas (FORTH/IEC-HT), 26504 Rio Patras, Greece 3 CBL-Patras, Patras Industrial Area, Block 1, 25018 Patras, Greece * Correspondence: [email protected]; Tel.: +30-2610-647600; Fax: +30-2610-647316 Academic Editor: Theodore Tselios Received: 23 December 2019; Accepted: 3 January 2020; Published: 5 January 2020 Abstract: Thioether containing peptides were obtained following three synthetic routes. In route A, halo acids esterified on 2-chlorotrityl(Cltr) resin were reacted with N-fluorenylmethoxycarbonyl (Fmoc) aminothiols. These were either cleaved from the resin to the corresponding (Fmoc-aminothiol) carboxylic acids, which were used as key building blocks in solid phase peptide synthesis (SPPS), or the N-Fmoc group was deprotected and peptide chains were elongated by standard SPPS. The obtained N-Fmoc protected thioether containing peptides were then condensed either in solution, or on solid support, with the appropriate amino components of peptides. In route B, the thioether containing peptides were obtained by the reaction of N-Fmoc aminothiols with bromoacetylated peptides, which were synthesized on Cltr-resin, followed by removal of the N-Fmoc group and subsequent peptide elongation by standard SPPS. In route C, the thioether containing peptides were obtained by the condensation of a haloacylated peptide synthesized on Cltr-resin and a thiol-peptide synthesized either on 4-methoxytrityl(Mmt) or trityl(Trt) resin. -
[2.2]Paracyclophanes- Structure and Reactivity Studies Von Der
Syntheses of Functionalised [2.2]Paracyclophanes- Structure and Reactivity Studies Von der Gemeinsamen Naturwissenschaftlichen Fakultät der Technischen Universität Carolo Wilhelmina zu Braunschweig zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr.rer.nat.) genehmigte D i s s e r t a t i o n von Swaminathan Vijay Narayanan aus Chennai (Madras) / India 1. Referent: Prof. Dr. Dr. h. c. Henning Hopf 2. Referentin: Prof. Dr. Monika Mazik eingereicht am: 20. Jan 2005 mündliche Prüfung (Disputation) am: 29. März 2005 Druckjahr 2005 Vorveröffentlichungen der Dissertation Teilergebnisse aus dieser Arbeit wurden mit Genehmigung der Gemeinsamen Naturwissenschaft-lichen Fakultät, vertreten durch die Mentorin oder den Mentor/die Betreuerin oder den Betreuer der Arbeit, in folgenden Beiträgen vorab veröffentlicht: Publikationen K. El Shaieb, V. Narayanan, H. Hopf, I. Dix, A. Fischer, P. G. Jones, L. Ernst & K. Ibrom.: 4,15-Diamino[2.2]paracyclophane as a starting material for pseudo-geminally substituted [2.2]paracyclophanes. Eur. J. Org. Chem.: 567-577 (2003). Die vorliegende Arbeit wurde in der Zeit von Oktober 2001 bis Januar 2004 am Institut für Organische Chemie der Technischen Universität Braunschweig unter der Leitung von Prof. Dr. Dr. h.c. Henning Hopf angefertigt. It is my great pleasure to express my sincere gratitude to Prof. Dr. Henning Hopf for his support, encouragement and guidance throughout this research work. I thank him a lot for his invaluable ideas and remarks which made this study very interesting. I admire deep from my heart his energetic way of working and his brilliant ideas which made possible this research work to cover a vast area. -
CV-PSB-August 2020
Curriculum Vitae Phil S. Baran Appointment: Scripps Research Professor, Department of Chemistry 10550 North Torrey Pines Road, BCC-436 La Jolla, California 92037 Telephone: (858) 784-7373 Facsimile: (858) 784-7575 Email: [email protected] Website: www.scripps.edu/chem/baran/ January, 2013 Darlene Shiley Professor of Chemistry April, 2009 Member, Skaggs Institute for Chemical Biology June, 2008 Professor of Chemistry July, 2006 Associate Professor of Chemistry (with Tenure) June, 2003 Assistant Professor of Chemistry Date/Place of Birth: 10 Aug 1977 / Denville, NJ, USA Citizenship: United States Education 2001 – 2003 Postdoctoral Associate Advisor: Professor E.J. Corey Harvard University, Cambridge, Massachusetts 1997 – 2001 Ph.D. Graduate Student in Chemistry Advisor: Professor K.C. Nicolaou The Scripps Research Institute, La Jolla, California 1995 – 1997 B.S. with Honors in Chemistry Advisor: Professor D.I. Schuster New York University, New York, New York 1991 – 1995 Simultaneous high school graduation from Mt. Dora High School and A.A. degree with honors, Lake Sumter Community College, Florida Awards • Inhoffen Medal, 2019 • Manchot Research Professorship, 2017 • Member, The National Academy of Sciences, 2017 • Emanuel Merck Lectureship, 2017 • Blavatnik National Laureate in Chemistry, 2016 • ACS Elias J. Corey Award, 2016 • Member, American Academy of Arts and Sciences, 2015 • College of Arts and Science Alumni Distinguished Service Award, New York University, 2015 • Reagent of the Year Award (EROS), 2015 • Mukaiyama Award, 2014 •