DOCSLIB.ORG

Chemical Ligation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Vol. 8, No. 1 Chemical Ligation Chemical Ligation by Click Chemistry Native Chemical Ligation Staudinger Ligation Diphenylphosphinemethanethiol: efficacious reagent for traceless Organic Azides and Staudinger ligation Azide Sources Functionalized Alkynes 2 Introduction Vol. 8 No. 1 More and more researchers face the task of selectively combining large molecules, attaching molecular probes, or covalently Aldrich Chemical Co., Inc. immobilizing substrates on surfaces. In particular when biopolymers Sigma-Aldrich Corporation and bioconjugates are involved there is an urgent need for mild and 6000 N. Teutonia Ave. biocompatible reaction conditions. A toolbox of several powerful Milwaukee, WI 53209, USA chemical ligation techniques already exists and is continually being expanded. In this issue of ChemFiles, we provide an overview of modern To Place Orders chemical ligation methods and introduce highly innovative and Telephone 800-325-3010 (USA) unique new tools for research at the interface between chemistry FAX 800-325-5052 (USA) and biology. The most prominent chemical ligation techniques (click chemistry, native chemical ligation, and Staudinger ligation) will be discussed. A comprehensive listing of available organic azides and functionalized alkynes rounds off this Customer & Technical Services issue of ChemFiles with valuable building blocks for click chemistry or Staudinger ligation. Customer Inquiries 800-325-3010 If you are unable to find the specific reagent you need, “Please Bother Us.” with your Technical Service 800-231-8327 suggestions at [email protected], or contact your local Sigma-Aldrich® office SAFC™ 800-244-1173 Introduction (see back cover). Custom Synthesis 800-244-1173 Flavors & Fragrances 800-227-4563 International 414-438-3850 CPR Let Discovery Put High Throughput 24-Hour Emergency 414-438-3850 Web Site sigma-aldrich.com Back in Your Operation! Email [email protected] Subscriptions The New Standard in Reagent Management To request your FREE subscription to ChemFiles, for Medicinal Chemistry and Organic Synthesis please contact us by: Flexible | Efficient | Convenient Phone: 800-325-3010 (USA) Mail: Attn: Marketing Communications • Internet-based reagent database and procurement Aldrich Chemical Co., Inc. • Powerful new batch-search and reporting capabilities Sigma-Aldrich Corporation • Determine price and availability from your desktop P.O. Box 355 Milwaukee, WI 53201-9358 • From micromoles to grams Email: [email protected] • 24–48 hour turnaround time for most compounds • Reduce waste; eliminate on-site stocking and inventory management International customers, please contact your • Specify vial type, atmosphere, labeling/bar-coding, local Sigma-Aldrich office. For worldwide contact packaging information, please see back cover. • No minimum order required ChemFiles are also available in PDF format on the Internet at sigma-aldrich.com/chemfiles. DiscoveryCPR Custom Packaged Reagents from To register for an Internet Aldrich brand products are sold through Sigma- Sigma-Aldrich puts high throughput ordering account Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its back into your chemistry! or to submit inquiries: products conform to the information contained in this and other Sigma-Aldrich publications. When projects demand custom arrays of reagents, DiscoveryCPR.com Purchaser must determine the suitability of the DiscoveryCPR can meet the challenge. product for its particular use. See reverse side of invoice or packing slip for additional terms and conditions of sale. sigma-aldrich.com All prices are subject to change without notice. ChemFiles (ISSN 1933–9658) is a publication of About Our Cover Aldrich Chemical Co., Inc. Aldrich is a member of the The cover structure depicts diphenylphosphinemethanethiol, the most efficacious Sigma-Aldrich Group. © 2008 Sigma-Aldrich Co. reagent known today to induce traceless Staudinger ligations (Raines ligation reagent). Diphenylphosphinemethanethiol can be obtained easily from the shelf-stable precursor 670359 by removing the acetyl and borane protective groups. 3 Chemical Ligation by Click Chemistry—A “Click” Away from Discovery The traditional process of drug discovery based on natural In an extensive study Finn and co-workers only recently showed secondary metabolites has often been slow, costly, and labor- that tris(2-benzimidazolylmethyl)amines (general structure in intensive. Even with the advent of combinatorial chemistry Figure 2) are the most promising family of accelerating ligands and high-throughput screening in the past two decades, the for the Cu catalyzed azide-alkyne cycloaddition reaction from generation of leads is dependent on the reliability of the individual among more than 100 mono-, bi-, and polydentate candidates.10 reactions to construct the new molecular framework. Under both preparative (high concentration, low catalyst loading) and dilute (lower substrate concentration, higher catalyst Click chemistry is a newer approach to the synthesis of drug- loading) conditions, these tripodal benzimidazole derivatives give like molecules that can accelerate the drug discovery process substantial improvements in rate and yields, with convenient by Click Chemistry Chemical Ligation by utilizing a few practical and reliable reactions. Sharpless and workup to remove residual Cu and ligand. co-workers have defined what makes a click reaction: one that is wide in scope and easy to perform, uses only readily available A new reagent developed by Carolyn R. Bertozzi and co-workers reagents, and is insensitive to oxygen and water. In fact, water is eliminates the toxicity to living cells that is usually associated with in several instances the ideal reaction solvent, providing the best the copper catalyzed Huisgen 1,3-dipolar cycloaddition.11 By using yields and highest rates. Reaction work-up and purification uses a difluorinated cyclooctyne (Figure 3) instead of the usual terminal benign solvents and avoids chromatography.1 alkyne a rapid cycloaddition reaction takes place even without a catalyst. The ring strain and the electron-withdrawing difluoro Of the reactions comprising the click universe, the “perfect” group activate the alkyne for copper-free click chemistry. This example is the Huisgen 1,3-dipolar cycloaddition of alkynes to method was used to attach fluorescent labels to cells with azide- azides to form 1,4-disubsituted-1,2,3-triazoles (Scheme 1). The containing sialic acid in their surface glycans. Thus, it was possible copper(I)-catalyzed reaction is mild and very efficient, requiring no to study the dynamics of glycan trafficking in living cells over the protecting groups and no purification in many cases.2 The azide course of 24 hours with no indication that the reaction or the and alkyne functional groups are largely inert towards biological labels perturb the process. This is an impressive example of how molecules and aqueous environments, which allows the use of copper-free click chemistry can be used as a biologically friendly the Huisgen 1,3-dipolar cycloaddition in target guided synthesis3 method to label and track biomolecules in living cells. and activity-based protein profiling,4 or the ligation of biopolymers to probes or surfaces.5 For example, Carell and co-workers Sigma-Aldrich® proudly offers a choice of catalysts and ligands demonstrated the labelling of alkyne modified DNA oligomers for the Huisgen cycloaddition reaction. Later sections in this issue with fluorescence probes by click chemistry.6 present a comprehensive overview of available organic azides, azide sources, and alkynes that may be applied in click chemistry. The triazole has similarities to the ubiquitous amide moiety found in nature. Thus triazole formation was used for the otherwise If you want to learn about hot new product additions to the difficult macrocyclization of a cyclic tetrapeptide analog to a click chemistry universe and other innovative areas of chemical potent tyrosinase inhibitor.7 synthesis as soon as they become available, please check our regularly updated product highlights at sigma-aldrich.com/ Additionally triazoles are nearly impossible to oxidize or reduce. chemicalsynthesis. This is a main reason why material science has discovered Huisgen cycloadditions as major ligation tools in diverse areas such as References: (1) For recent reviews, see: (a) Kolb, H. C.; Sharpless, K. B. Drug Discovery polymer science or nanoelectronics.8 Today 2003, 8, 1128. (b) Kolb, H. C. et al. Angew. Chem. Int. Ed. 2001, 40, 2004. (2)(a) Rostovtsev, V. V.; Green, L.G.; Fokin, V.V.; Sharpless, K.B. Angew. Chem. Int. Ed. Using Cu(II) salts with ascorbate has been the method of 2002, 41, 2596. (b) Tornøe, C. W. et al. J. Org. Chem. 2002, 67, 3057. (3)(a) Manetsch, choice for the preparative synthesis of 1,2,3-triazoles, but it is R. et al. J. Am. Chem. Soc. 2004, 126, 12809. (b) Lewis, W.G. et al. Angew. Chem. Int. Ed. 2002, 41, 1053. (4) Speers, A. E. J. Am. Chem. Soc. 2003, 125, 4686. (5) Wolfbeis, problematic in bioconjugation applications. However, O.S. Angew. Chem. Int. Ed. 2007, 46, 2980. (6) Gierlich, J.; Burley, G.A.; Gramlich, tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine, TBTA (Figure 1), P.M.E.; Hammond, D.M.; Carell, T. Org. Lett. 2006, 8, 3639. (7) Bock, V.D.; Perciaccente, has been shown to effectively enhance the copper-catalyzed R.; Jansen, T.P.; Hiemstra, H.; Maarseveen, J.H. Org. Lett. 2006, 8, 919. (8) Lutz, J.-F. 9 Angew. Chem. Int. Ed. 2007, 46, 1018. (9) Chan, T.R. et al. Org. Lett 2004, 6, 2853. cycloaddition without damaging biological scaffolds. (10) Rodionov, V. O.; Presolski, S. I.; Gardinier, S.; Lim, Y.-H.; Finn, M. G. J. Am. Chem. Soc. 2007, 129, 12696. (11) Baskin, J.M.; Prescher, J.A.; Laughlin, S.T.; Agard, N.J.; Chang, P.V.; Miller, I.A.; Lo, A.; Codelli, J.A.; Bertozzi, C.R. PNAS 2007, 104, 16793. R2 1 mol% CuSO4 N N 2 N N 5 mol% sodium ascorbate N N R 1 N N R H O/tBuOH 2:1 1 R 2 R R rt, 8 h N R = H or -(CH ) CO K Scheme 1 N 2 4 2 N N N N N R Figure 2 N N N N O R F N N N H F N N R = fluorescent dye or biotin Figure 3 Figure 1 Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
Recommended publications
  • Investigation of Base-Free Copper-Catalysed Azide–Alkyne Click Cycloadditions (Cuaac) in Natural Deep Eutectic Solvents As Green and Catalytic Reaction Media

    Investigation of Base-Free Copper-Catalysed Azide–Alkyne Click Cycloadditions (Cuaac) in Natural Deep Eutectic Solvents As Green and Catalytic Reaction Media

    Investigation of Base-free Copper-Catalysed Azide–Alkyne Click Cycloadditions (CuAAc) in Natural Deep Eutectic Solvents as Green and Catalytic Reaction Media Salvatore V. Giofrè,1* Matteo Tiecco,2* Angelo Ferlazzo,3 Roberto Romeo,1 Gianluca Ciancaleoni,4 Raimondo Germani2 and Daniela Iannazzo3 1. Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, Viale Annunziata, I-98168 Messina, Italy. 2. Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia, via Elce di Sotto 8, I- 06123 Perugia, Italy. 3. Dipartimento di Ingegneria, Università of Messina, Contrada Di Dio, I-98166 Messina, Italy 4. Dipartimento di Chimica e Chimica Industriale (DCCI), Università di Pisa, Via Giuseppe Moruzzi, 13, I-56124 Pisa, Italy. * Corresponding authors Email addresses: [email protected] (Salvatore V. Giofrè); [email protected] (Matteo Tiecco). ABSTRACT The click cycloaddition reaction of azides and alkynes affording 1,2,3-triazoles is a transformation widely used to obtain relevant products in chemical biology, medicinal chemistry, materials science and other fields. In this work, a set of Natural Deep Eutectic Solvents (NADESs) as “active” reaction media has been investigated in the copper-catalysed azide–alkyne cycloaddition reactions (CuAAc). The use of these green liquids as green and catalytic solvents has shown to improve the reaction effectiveness, giving excellent yields. The NADESs proved to be “active” in this transformation for the absence of added bases in all the performed reactions and in several cases for their reducing capabilities. The results were rationalized by DFT calculations which demonstrated the involvement of H-bonds between DESs and alkynes as well as a stabilization of copper catalytic intermediates.
  • Amide-Forming Chemical Ligation Via O-Acyl Hydroxamic Acids

    Amide-Forming Chemical Ligation Via O-Acyl Hydroxamic Acids

    Amide-forming chemical ligation via O-acyl hydroxamic acids Daniel L. Dunkelmanna,1, Yuki Hirataa,1, Kyle A. Totaroa, Daniel T. Cohena, Chi Zhanga, Zachary P. Gatesa,2, and Bradley L. Pentelutea,2 aDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved February 28, 2018 (received for review October 20, 2017) The facile rearrangement of “S-acyl isopeptides” to native peptide ligation have relied on the use of thiol nucleophiles to form bonds via S,N-acyl shift is central to the success of native chemical S-acyl isopeptides, which undergo rapid S,N-acyl shifts through ligation, the widely used approach for protein total synthesis. small rings. An exception is the use of selenocysteine (23–26) α Proximity-driven amide bond formation via acyl transfer reactions and peptide- selenoesters (27, 28), which exhibit analogous but in other contexts has proven generally less effective. Here, we heightened reactivity. show that under neutral aqueous conditions, “O-acyl isopeptides” We sought to expand the scope of nucleophiles that might be derived from hydroxy-asparagine [aspartic acid-β-hydroxamic acid; employed in acyl transfer-based chemical ligation, and to rein- Asp(β-HA)] rearrange to form native peptide bonds via an O,N-acyl vestigate the possibility of O,N-acyl transfer across medium-size shift. This process constitutes a rare example of an O,N-acyl shift rings. Hydroxamic acids (29) were found to be sufficiently re- that proceeds rapidly across a medium-size ring (t1/2 ∼ 15 min), active to enable the formation of an O-acyl isopeptide from a α and takes place in water with minimal interference from hydroly- peptide- thioester and an N-terminal Asp(β-HA)-peptide at sis.
  • Organic Synthesis: Handout 1

    Organic Synthesis: Handout 1

    Prof Tim Donohoe: Strategies and Taccs in Organic Synthesis: Handout 1 Organic Synthesis III 8 x 1hr Lectures: Michaelmas Term Weeks 5-8 2016 Mon at 10am; Wed at 9am Dyson Perrins lecture theatre Copies of this handout will be available at hEp://donohoe.chem.ox.ac.uk/page16/index.html 1/33 Prof Tim Donohoe: Strategies and Taccs in Organic Synthesis: Handout 1 Organic Synthesis III Synopsis 1) Introduc5on to synthesis: (i) Why do we want to synthesise molecules- what sort of molecules do we need to make? (ii) What aspects of selecvity do we need to accomplish a good synthesis (chemo-, regio- and stereoselecvity)? (iii) Protecng group chemistry is central to any syntheAc effort (examples and principles) (iv) What is the perfect synthesis (performed in industry versus academia)? 2) The chiral pool: where does absolute stereochemistry come from? 3) Retrosynthesis- learning to think backwards (revision from first and second year). Importance of making C-C bonds and controlling oxidaAon state. Umpolung 4) Some problems to think about 5) Examples of retrosynthesis/synthesis in ac5on. 6) Ten handy hints for retrosynthesis 7) Soluons to the problems Recommended books: General: Organic Chemistry (Warren et al) Organic Synthesis: The DisconnecRon Approach (S. Warren) Classics in Total Synthesis Volumes I and II (K. C. Nicolaou) The Logic of Chemical Synthesis (E. J. Corey) 2/33 View Article Online / Journal Homepage / Table of Contents for this issue 619461 Strychniqae and BYucine. Pavt XLII. 903 Prof Tim Donohoe: Strategies and Taccs in Organic Synthesis: Handout 1 (i) Why do we want to synthesise complex molecules? Isolated from the Pacific Yew in 1962 Prescribed for prostate, breast and ovarian cancer Unique mode of acRon 1x 100 year old tree = 300 mg Taxol Isolated in 1818- poisonous Stuctural elucidaon took R.
  • Artificial Intelligence for Computer-Aided Synthesis

    Artificial Intelligence for Computer-Aided Synthesis

    ORIGINAL RESEARCH published: 04 August 2020 doi: 10.3389/fceng.2020.00005 Artificial Intelligence for Computer-Aided Synthesis In Flow: Analysis and Selection of Reaction Components Pieter P. Plehiers 1,2, Connor W. Coley 1, Hanyu Gao 1, Florence H. Vermeire 1, Maarten R. Dobbelaere 2, Christian V. Stevens 3, Kevin M. Van Geem 2* and William H. Green 1* 1 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States, 2 Laboratory for Chemical Technology, Department of Materials, Textiles and Chemical Engineering, Ghent University, Ghent, Belgium, 3 SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent Edited by: University, Ghent, Belgium René Schenkendorf, Technische Universitat Braunschweig, Germany Computer-aided synthesis has received much attention in recent years. It is a challenging Reviewed by: topic in itself, due to the high dimensionality of chemical and reaction space. It becomes Richard Anthony Bourne, even more challenging when the aim is to suggest syntheses that can be performed in University of Leeds, United Kingdom Alexei Lapkin, continuous flow. Though continuous flow offers many potential benefits, not all reactions University of Cambridge, are suited to be operated continuously. In this work, three machine learning models United Kingdom have been developed to provide an assessment of whether a given reaction may benefit *Correspondence: from continuous operation, what the likelihood of success in continuous flow is for a Kevin M. Van Geem [email protected] certain set of reaction components (i.e., reactants, reagents, solvents, catalysts, and William H. Green products) and, if the likelihood of success is low, which alternative reaction components [email protected] can be considered.
  • Organoboranes in Organic Syntheses Including Suzuki Coupling Reaction

    Organoboranes in Organic Syntheses Including Suzuki Coupling Reaction

    HETEROCYCLES, Vol. 80, No. 1, 2010 15 HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 15 - 43. © The Japan Institute of Heterocyclic Chemistry DOI: 10.3987/COM-09-S(S)Summary ORGANOBORANES IN ORGANIC SYNTHESES INCLUDING SUZUKI COUPLING REACTION Akira Suzuki In 1962 I had a lively interest in Wacker reaction [the oxidation of ethylene to acetaldehyde in the presence of palladium chloride and cupric chloride (Angew. Chem. 1959, 71, 176)] and began a literature survey. One Saturday afternoon during that time, I went a bookstore in Sapporo to look at new chemistry books and found a red and black two-tone colored book on the shelf that did not look like a chemistry book. The book was "Hydroboration" written by Professor Herbert C. Brown of Purdue University. It seemed to be an interesting book, so, I bought it. This book changed the course of my career, and my fascination with the chemistry of hydroboration reaction and organoboron compounds thus prepared by hydroboration began after reading the book. I immediately wrote to Professor Brown requesting to work as a postdoctoral research fellow. At that time Professor Brown was at Heidelberg in Germany as a visiting professor. He kindly wrote me a letter of acceptance, and I began a study of the stereochemistry of hydroboration reaction at Purdue (1963-65). Through this work I came to understand hydroboration and the interesting characteristics of organoboranes. My family (wife and two small girls) and I had a very good time there and made good friends. Of course I enjoyed chemistry. After a stay of about two years at Purdue, I returned to Japan with my family at the end of March 1965.
  • Syntheses and Eliminations of Cyclopentyl Derivatives David John Rausch Iowa State University

    Syntheses and Eliminations of Cyclopentyl Derivatives David John Rausch Iowa State University

    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1966 Syntheses and eliminations of cyclopentyl derivatives David John Rausch Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Rausch, David John, "Syntheses and eliminations of cyclopentyl derivatives " (1966). Retrospective Theses and Dissertations. 2875. https://lib.dr.iastate.edu/rtd/2875 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. This dissertation has been microfilmed exactly as received 66—6996 RAUSCH, David John, 1940- SYNTHESES AND ELIMINATIONS OF CYCLOPENTYL DERIVATIVES. Iowa State University of Science and Technology Ph.D., 1966 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan SYNTHESES AND ELIMINATIONS OF CYCLOPENTYL DERIVATIVES by David John Rausch A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Subject: Organic Chemistry Approved : Signature was redacted for privacy. Signature was redacted for privacy. Head of Major Department Signature was redacted for privacy. Iowa State University Of Science and Technology Ames, Iowa 1966 ii TABLE OF CONTENTS VITA INTRODUCTION HISTORICAL Conformation of Cyclopentanes Elimination Reactions RESULTS AND DISCUSSION Synthetic Elimination Reactions EXPERIMENTAL Preparation and Purification of Materials Procedures and Data for Beta Elimination Reactions SUMMARY LITERATURE CITED ACKNOWLEDGEMENTS iii VITA The author was born in Aurora, Illinois, on October 24, 1940, to Mr.
  • Chemistry 301-301A - Hour Examination #3, December 11, 2003

    Chemistry 301-301A - Hour Examination #3, December 11, 2003

    Chemistry 301-301A - Hour Examination #3, December 11, 2003 “.....as we know, there are known unknowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns - the ones we don't know we don't know.” Donald Rumsfeld (winner of a British award given to the worst mangler of the English language in 2003) “I know, a proof is a proof. What kind of a proof is a proof? A proof is a proof and when you have a good proof it's because it's proven." Jean Chrétien (hon. mention for the same award) 1[18 points] (a) Acid-catalyzed addition of water to 3-methyl-1-butene (1) results in formation of large amounts of a rearranged alcohol (2), in addition to the expected alcohol (3). Explain, with excellent arrow formalisms. H2O + H O+ 3 OH OH 1 3 2 (b) On the other hand hydroboration of 1, followed by oxidation, does not lead to any rearranged product. Only alcohol 4 is formed. Explain. Detailed mechanisms are not needed here, but a drawing of the transition state for the hydroboration step is. 1. BH3 OH 2. HOOH/HO – 1 4 (c) But there are some strange things that happen in hydroboration. For example when 2-methyl-2-butene (5) is hydroborated at high temperature, then treated with HOOH/HO–, alcohol 4 is still one of the products. Explain mechanistcally. Hint: at high temperature hydroboration is reversible.
  • Chapter 8 - Alkynes: an Introduction to Organic Synthesis

    Chapter 8 - Alkynes: an Introduction to Organic Synthesis

    Chapter 8 - Alkynes: An Introduction to Organic Synthesis Draw structures corresponding to each of the following names. 1. ethynylcyclopropane Answer: CCH 2. 3,10-dimethyl-6-sec-butylcyclodecyne Answer: 3. 4-bromo-3,3-dimethyl-1-hexen-5-yne CH3 Br Answer: H 2C CH C CH C C H CH3 4. acetylene Answer: H CCH Provide names for each compound below. CH3 5. CH3C CCHCH2CH2CH3 Answer: 4-methyl-2-heptyne CH 3 6. CCH Answer: 1-ethynyl-2-methylcyclopentane Test Items for McMurry’s Organic Chemistry, Seventh Edition 59 The compound below has been isolated from the safflower plant. Consider its structure to answer the following questions. H H CCCCCCCC H H3C C C C H H C H H 7. What is the molecular formula for this natural product? Answer: C13H10 8. What is the degree of unsaturation for this compound? Answer: We can arrive at the degree of unsaturation for a structure in two ways. Since we know that the degree of unsaturation is the number of rings and/or multiple bonds in a compound, we can simply count them. There are three double bonds (3 degrees) and three triple bonds (six degrees), so the degree of unsaturation is 9. We can verify this by using the molecular formula, C13H10, to calculate a degree of unsaturation. The saturated 13-carbon compound should have the base formula C13H28, so (28 - 10) ÷ 2 = 18 ÷ 2 = 9. 9. Assign E or Z configuration to each of the double bonds in the compound. Answer: H H E CCCCCCCCE H H3C C C C H H C H H 10.
  • Retrosynthetic Design of Metabolic Pathways to Chemicals Not Found in Nature

    Retrosynthetic Design of Metabolic Pathways to Chemicals Not Found in Nature

    Retrosynthetic design of metabolic pathways to chemicals not found in nature The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Lin, Geng-Min et al. "Retrosynthetic design of metabolic pathways to chemicals not found in nature." Biology 14 (April 2019): 82-107 © 2019 The Authors As Published http://dx.doi.org/10.1016/J.COISB.2019.04.004 Publisher Elsevier BV Version Final published version Citable link https://hdl.handle.net/1721.1/125854 Terms of Use Creative Commons Attribution-NonCommercial-NoDerivs License Detailed Terms http://creativecommons.org/licenses/by-nc-nd/4.0/ Available online at www.sciencedirect.com Current Opinion in ScienceDirect Systems Biology Retrosynthetic design of metabolic pathways to chemicals not found in nature Geng-Min Lin1, Robert Warden-Rothman1 and Christopher A. Voigt Abstract simpler chemical building blocks derived from pe- Biology produces a universe of chemicals whose precision and troleum or other sources [1]. Chemicals that are large complexity is the envy of chemists. Over the last 30 years, the and complex with many functional groups and ster- expansive field of metabolic engineering has many successes eocenters have required Herculean efforts to build; in optimizing the overproduction of metabolites of industrial in- for example, halichondrin B has 32 stereocenters (4 terest, including moving natural product pathways to production billion isomers) and requires a sprawling total syn- hosts (e.g., plants to yeast). However, there are stunningly few thesis whose longest linear path is 47 reactions [2]. examples where enzymes are artificially combined to make a Solutions have been found to incredibly challenging chemical that is not found somewhere in nature.
  • Hydrogenationn of 4-Octyne Catalyzedd by Pd[(M^W'- (CF3)2C6H3)) Bian](Ma) in THF

    Hydrogenationn of 4-Octyne Catalyzedd by Pd[(M^W'- (CF3)2C6H3)) Bian](Ma) in THF

    UvA-DARE (Digital Academic Repository) Palladium-catalyzed stereoselective hydrogenation of alkynes to (Z)-alkenes in common solvents and supercritical CO2 Kluwer, A.M. Publication date 2004 Link to publication Citation for published version (APA): Kluwer, A. M. (2004). Palladium-catalyzed stereoselective hydrogenation of alkynes to (Z)- alkenes in common solvents and supercritical CO2. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:04 Oct 2021 5 Kineti5 cc study and Spectroscopic Investigationn of the semi- hydrogenationn of 4-octyne catalyzedd by Pd[(m^w'- (CF3)2C6H3)) bian](ma) in THF 5.11 Introduction Homogeneouss hydrogenation by transition metal complexes has played a key role in the fundamental understandingg of catalytic reactions and has proven to be of great utility in practical applications.
  • Protein Ligation: an Enabling Technology for the Biophysical Analysis of Proteins Vasant Muralidharan & Tom W Muir

    Protein Ligation: an Enabling Technology for the Biophysical Analysis of Proteins Vasant Muralidharan & Tom W Muir

    REVIEW Protein ligation: an enabling technology for the biophysical analysis of proteins methods Vasant Muralidharan & Tom W Muir Biophysical techniques such as fluorescence spectroscopy and nuclear magnetic .com/nature e resonance (NMR) spectroscopy provide a window into the inner workings of proteins. These approaches make use of probes that can either be naturally present within the .natur w protein or introduced through a labeling procedure. In general, the more control one has over the type, location and number of probes in a protein, then the more information one can extract from a given biophysical analysis. Recently, two related approaches have http://ww emerged that allow proteins to be labeled with a broad range of physical probes. Expressed oup r protein ligation (EPL) and protein trans-splicing (PTS) are both intein-based approaches G that permit the assembly of a protein from smaller synthetic and/or recombinant pieces. Here we provide some guidelines for the use of EPL and PTS, and highlight how the lishing b dovetailing of these new protein chemistry methods with standard biophysical techniques Pu has improved our ability to interrogate protein function, structure and folding. Nature 6 An intimate understanding of protein structure and studying protein structure and function in vitro. The goal 200 function remains a principal goal of molecular biology. of this review is to provide an overview of these protein- © The seemingly byzantine structure-activity relationships engineering approaches, with a particular eye toward the underlying protein function make this endeavor extreme- nonspecialist interested in using these techniques to gener- ly challenging and one that requires ever more sophistica- ate labeled proteins for biophysical studies.
  • Strategies for the Synthesis of Ynamides

    Strategies for the Synthesis of Ynamides

    I. SYNTHESIS OF INDOLINES AND INDOLES VIA INTRAMOLECULAR [4 + 2] CYCLOADDITION OF YNAMIDES AND CONJUGATED ENYNES II. SYNTHESIS OF NITROGEN HETEROCYCLES IN SUPERCRITICAL CARBON DIOXIDE by Joshua Ross Dunetz B. A., Chemistry Haverford College, 2000 SUBMITTED TO THE DEPARTMENT OF CHEMISTRY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY September 2005 © Massachusetts Institute of Technology, 2005 All rights reserved Signature of Author .................... ·Department of Chemistry September 1, 2005 a( / Certified by ................................... ................................ Rick L. Danheiser Arthur C. Cope Professor of Chemistry, Thesis Supervisor Acceptedby......................... ............................................ I.... 7 Robert W. Field MASSACHUSETSINSTn '.vE I F TrwfhNl erv-v I Chairman, Department Committee on Graduate Students OCT 1 2005 d }cl/CF , LIBRARIES ~ This doctoral thesis has been examined by a committee in the Department of Chemistry as follows: Professor Timothy F. Jamison . ... Chairman Professor Rick L. Danheiser ........... ... ............................ Thesis Supervisor Professor Barbara Imperiali. ...... ................................................ 2 ACKNOWLEDGMENTS All acknowledgments must begin with my thesis advisor, Rick Danheiser. I first remember meeting him at the Cambridge Brewing Company during recruiting weekend five years ago, and we sat for hours in the restaurant discussing the merits of the 2000 New York Mets and whether one of our favorite baseball teams had a chance to make the playoffs that year. Ultimately, I decided to attend MIT with the hope of joining his group, and during my time in his laboratory Rick has been an excellent mentor and chemistry role model. I continue to be amazed not only by the extent of his knowledge, but also by his ability to articulate chemical principles in an easy and straightforward manner.