DOCSLIB.ORG

Ethylene Biosynthesis: Processing of a Substrate Analog Supports a Radical Mechanism for the Ethylene-Forming Enzyme Michael C Pirrung, Jun Cao and Jrlung Chen

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ethylene Biosynthesis: Processing of a Substrate Analog Supports a Radical Mechanism for the Ethylene-Forming Enzyme Michael C Pirrung, Jun Cao and Jrlung Chen View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Research Paper 49 Ethylene biosynthesis: processing of a substrate analog supports a radical mechanism for the ethylene-forming enzyme Michael C Pirrung, Jun Cao and Jrlung Chen Background: The chemical mechanism of the final step of ethylene biosynthesis Address: Department of Chemistry, P.M. Gross (the conversion of 1 -aminocyclopropanecarboxylic acid, ACC, to ethylene by Chemical Laboratory, Duke University, Durham, North Carolina 27708-0346, USA. ACC oxidase, the ethylene-forming enzyme, EFE) is poorly understood. Two possibilities have been suggested: a radical mechanism and an /II-hydroxylation Correspondence: Michael C Pirrung mechanism. We investigated reaction pathways available to radical intermediates in this reaction using an ACC analog, 1 -aminocyclobutanecarboxylic acid Key words: 1 -aminocyclobutanecarboxylate, biosynthesis, ethylene, hydroxylation, radical (ACBC) as a substrate. Received: 14 October 1997 Results: ACBC was converted to dehydroproline (Al-pyrroline-2-carboxylic acid) Revisions requested: 14 November 1997 by the EFE via a ring expansion process. The possibility that an N-hydroxy- Revisions received: 18 November 1997 aminoacid (produced during two-electron oxidation) acts as an intermediate in this Accepted: 18 November 1997 process was eliminated by control experiments. Chemical model reactions Published: 15 January 1998 involving two-electron oxidants, such as a positive halogen (X+), which presumably generate N-halo derivatives, produce only decarboxylation products. Chemistry & Biology January 1998, 5:49-57 http://biomednet.com/elecref/1074552100500049 Radical-based oxidants, in contrast, generate dehydroproline. Model reactions involving sequential single-electron transfer mechanisms also produce 0 Current Biology Ltd ISSN 1074-5521 dehydroproline; thus our results support the proposal that the EFE-catalyzed step of ethylene biosynthesis proceeds using a radical-based mechanism. Conclusions: Our results provide support for a radical mechanism in the final step of ethylene biosynthesis and refute an alternative IV-hydroxylation mechanism. This work extends the idea that the intrinsic chemical reactivity of a high energy iron-oxo intermediate can account for the observed products in ethylene biosynthesis. Introduction The availability of purified EFE has allowed the determi- The biosynthesis of ethylene from l-aminocyclopropane- nation of a number of the key characteristics of its reac- carboxylic acid (ACC) in higher plants is a fascinating tion (Figure 1). One question of particular interest is the process [l]. Its study has been challenging because the fate of the four oxidizing equivalents of O,, as the conver- enzyme that catalyzes this reaction was for some time dif- sion of ACC to ethylene is only a two-electron oxidation ficult to isolate and is very unstable. Consequently, much process. EFE belongs to a family of non-heme iron oxy- initial work was conducted using classical methods for the genases; in these enzymes, a-ketoglutarate is often a study of biosynthesis [Z]; labeled substrates were fed to cosubstrate that consumes the remaining two oxidizing plants, followed by product analysis using physical equivalents during its conversion to CO, and succinate. methods. Isolation of ACC oxidase, also known as the eth- Ascorbate is required for EFE activity, however, and one ylene-forming enzyme (EFE), in homogeneous form from group has reported that it is oxidized to dehydroascorbate apple fruit [3-61 has facilitated more rigorous study. We [5]. On the other hand, inhibition by a-keto acids has also have studied the inhibition of this enzyme with different been reported [14]. The enzyme also experiences signifi- amino acid hydroxamates, and their varying potency sug- cant auto-inactivation [ 1,5]. gests that they act not by simply removing iron from the enzyme, but through both metal chelation and hydropho- Known alternate substrates for the EFE include Z-alkyl bic interactions in the active site [7]. The most potent ACC analogues of specific stereochemistry (a cis relation inhibitor, ACC-hydroxamate, has a Ki comparable to the of the nitrogen and alkyl group is required) [16-181 and substrate Km. EFE has now been isolated from a number a-aminoisobutyric acid (AIB; Figure 2) [19]. The former of sources [8,9], and recombinant bacterial and yeast are processed to the corresponding l-alkenes, whereas the expression systems have been developed [lo-121. Het- latter is converted to CO, and (presumably) acetone erologously-expressed recombinant tomato enzyme, inter- imine. Gibson &al: [13] have identified a similar oxidative estingly, behaves differently with hydroxamates than does decarboxylation reaction, also catalyzed by the EFE, in the native apple enzyme [ 131. the processing of D-valine to isobutyraldehyde. 50 Chemistry & Biology 1998, Vol 5 No 1 Figure 1 Figure 2 (a) HPC=CHz + HCN + COP + 2 Hz0 allo-coronamic acid HO 0 W 0 *co* I 0 0 EFE *oo ----w + HO 0 >ic OH OH NH3 @ x;? aminoisobutyric acid OH OH (AR Chemistry & Biology 2) Chemists & Bioloav Possible stoichiometry for ethylene biosynthesis from 1 -amino- Alternative EFE substrates and their products. (a) Allo-coronamic acid, cyclopropanecarboxylic acid (ACC; 1). The reaction is catalyzed by a 2-alkyl ACC analogue, is processed by the EFE forming a 1 -alkene. ACC oxidase, also known as the ethylene-forming enzyme (EFE). (b) Aminoisobutyric acid (AIB; 2) can also be processed by the EFE to generate carbon dioxide and acetone imine. As a result of previous mechanistic studies, including an electrochemical oxidation study, a sequential single-elec- and oxidative ring closure in a number of biosynthetic tron transfer mechanism for ethylene biosynthesis has pathways found in microorganisms and higher plants been proposed [ZO], which is shown in Figure 3. We sug- further suggests that it uses an iron-oxo intermediate; gested that a primary role of the EFE is to generate a that the required radical cation could be generated by substrate radical, specifically radical cation 3 (Figure 3); a electron transfer from the amino group of ACC provides precedent for this kind of radical generation was estab- further support for this idea. Kinetic measurements on lished in earlier studies on the inactivation of cytochrome cyclopropylamine radical cations are not available, but it P450 (iron-oxo) enzymes by cyclopropylamines [21,22]. is possible to estimate their reactivity. The Z-phenylcy- Because the pH environment of these enzyme active clopropylaminyl radical is known to open to a stabilized sites is unknown and the aminyl radical and radical radical with a rate constant > 1011 s-r [28] and, based on cation differ only by protonation, with an approximate earlier studies and the known effects of the phenyl group p&=7 for the dialkylaminyl radicals (231, it is difficult to on ring-opening rates, the unsubstituted cyclopropy- exclude the corresponding aminyl radical as a possible laminyl radical would be expected to open at a rate of early intermediate in ethylene biosynthesis. On the other -lOa s-l. Amine cation radicals have been shown to hand, studies by electron paramagnetic resonance (EPR) undergo rearrangements up to 103-fold faster than their spectroscopy in a frozen matrix of inert gas of the radical cognate aminyl radicals [23], which suggests a rate con- cation and aminyl radical of cyclopropylamine and their stant for ring opening of > 101’ssl (to produce 4; ring-opened isomers [24] have shown that opening of the Figure 3). One inconsistency in the kinetic picture, cur- aminyl radical leads quickly to internal hydrogen-atom rently under investigation, is that hydroxyl rebound to 4 transfer from the N-H species to generate an iminyl might occur if its conversion to ethylene is no faster than radical. This species is not consistent with the require- 10s s-l. Oxygen rebound rates in non-heme iron enzymes ments for ethylene production as it bears an ethyl unit; an are addressed below. aminyl radical mechanism is not favored because of this. Figure 3 The intrinsic reactivity of 3 and subsequent intermediates (shown in Figure 3) should lead readily to ethylene pro- duction (see below) [Z]. We have proposed that the ACC- radical cation preferentially undergoes ring opening in . order to release cyclopropane ring strain. The production pKas7 of the radical 3 is evidently the rate-determining step [IS], 11 as the ring opening is an irreversible and exothermic reac- tion 1231 (calculated to be 7 kcalmol-l) [26] and, based on p;Q.+ ~$-+ .-Hcy2- -H+_qHco2- the processing of a radical clock substrate [27], which pro- 3 42 5 vides an internal kinetic competition after the rate-deter- +HNC-C02- - HCN + CO2 + H+ mining step, the conversion of 4 to ethylene cannot be faster than lo* s-l. 7 Chemistry & Biolog) That the EFE is closely related to a group of non-heme The sequential single electron transfer model for ethylene biosynthesis. iron proteins that catalyse hydroxylations, epoxidations, Research Paper Ethylene biosynthesis Pirrung, Cao and Chen 51 Figure 4 the path for ACBC (X=CH,); ring opening for ACBC should be about lo3 s-l slower than for ACC, whatever its rate, and we expected N-hydroxylation to be more favored. co*- NH x NHp+* 8 Recent data from Silverman and co-workers [31] on the Chemists & Bioloav mechanism-based inactivation by, and processing of, sub- strate analogues of monoamine oxidase (MAO) give A possible mechanism
Load more

Recommended publications
  • A Photoionization Reflectron Time‐Of‐Flight Mass Spectrometric
    Articles ChemPhysChem doi.org/10.1002/cphc.202100064 A Photoionization Reflectron Time-of-Flight Mass Spectrometric Study on the Detection of Ethynamine (HCCNH2) and 2H-Azirine (c-H2CCHN) Andrew M. Turner,[a, b] Sankhabrata Chandra,[a, b] Ryan C. Fortenberry,*[c] and Ralf I. Kaiser*[a, b] Ices of acetylene (C2H2) and ammonia (NH3) were irradiated with 9.80 eV, and 10.49 eV were utilized to discriminate isomers energetic electrons to simulate interstellar ices processed by based on their known ionization energies. Results indicate the galactic cosmic rays in order to investigate the formation of formation of ethynamine (HCCNH2) and 2H-azirine (c-H2CCHN) C2H3N isomers. Supported by quantum chemical calculations, in the irradiated C2H2:NH3 ices, and the energetics of their experiments detected product molecules as they sublime from formation mechanisms are discussed. These findings suggest the ices using photoionization reflectron time-of-flight mass that these two isomers can form in interstellar ices and, upon spectrometry (PI-ReTOF-MS). Isotopically-labeled ices confirmed sublimation during the hot core phase, could be detected using the C2H3N assignments while photon energies of 8.81 eV, radio astronomy. 1. Introduction acetonitrile (CH3CN; 1) and methyl isocyanide (CH3NC; 2) ‘isomer doublet’ (Figure 2) – the methyl-substituted counterparts of For the last decade, the elucidation of the fundamental reaction hydrogen cyanide (HCN) and hydrogen isocyanide (HNC) – has pathways leading to structural isomers – molecules with the been detected toward the star-forming region SgrB2.[4,8–9] same molecular formula, but distinct connectivities of atoms – However, none of their higher energy isomers has ever been of complex organic molecules (COMs) in the interstellar identified in any astronomical environment: 2H-azirine (c- [10–14] [15–19] medium (ISM) has received considerable interest from the NCHCH2; 3), ethynamine (HCCNH2; 4), ketenimine [1–3] [20] [21] astrochemistry and physical chemistry communities.
    [Show full text]
  • A Chemical Kinetics Network for Lightning and Life in Planetary Atmospheres P
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by St Andrews Research Repository The Astrophysical Journal Supplement Series, 224:9 (33pp), 2016 May doi:10.3847/0067-0049/224/1/9 © 2016. The American Astronomical Society. All rights reserved. A CHEMICAL KINETICS NETWORK FOR LIGHTNING AND LIFE IN PLANETARY ATMOSPHERES P. B. Rimmer and Ch Helling School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, UK; [email protected] Received 2015 June 3; accepted 2015 October 22; published 2016 May 23 ABSTRACT There are many open questions about prebiotic chemistry in both planetary and exoplanetary environments. The increasing number of known exoplanets and other ultra-cool, substellar objects has propelled the desire to detect life andprebiotic chemistry outside the solar system. We present an ion–neutral chemical network constructed from scratch, STAND2015, that treats hydrogen, nitrogen, carbon, and oxygen chemistry accurately within a temperature range between 100 and 30,000 K. Formation pathways for glycine and other organic molecules are included. The network is complete up to H6C2N2O3. STAND2015 is successfully tested against atmospheric chemistry models for HD 209458b, Jupiter, and the present-day Earth using a simple one- dimensionalphotochemistry/diffusion code. Our results for the early Earth agree with those of Kasting for CO2,H2, CO, and O2, but do not agree for water and atomic oxygen. We use the network to simulate an experiment where varied chemical initial conditions are irradiated by UV light. The result from our simulation is that more glycine is produced when more ammonia and methane is present.
    [Show full text]
  • The WMS Model
    Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics. This journal is © the Owner Societies 2018 S-1 ELECTRONIC SUPPLEMENTARY INFORMATION OCT. 8, 2018 Extrapolation of High-Order Correlation Energies: The WMS Model Yan Zhao,a Lixue Xia,a Xiaobin Liao,a Qiu He,a Maria X. Zhao,b and Donald G. Truhlarc aState Key Laboratory of Silicate Materials for Architectures,International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, People’s Republic of China. bLynbrook High School, 1280 Johnson Avenue, San Jose, California 95129 cDepartment of Chemistry and Supercomputing Institute, University of Minnesota, 207 Pleasant Street S.E., Minneapolis, MN 55455-0431 TABLE OF CONTENTS Table S1: Calculated classical barrier heights (kcal/mol) for the DBH24-W4 database S-2 Table S2: RMSE of the scalar relativistic contribution in WMS (kcal/mol) S-3 Table S3: RMSE of the composite methods for the W4-17 database (kcal/mol) S-4 Table S4: Calculated Born-Oppenheimer atomization energy (kcal/mol) for the W4-17 database S-5 Table S5: Example input file for a WMS calculation: the H2O molecule S-11 Table S6: Example input file for a WMS calculation: the CH3 radical S-12 Table S7. perl scripts for performing WMS calculations S-13 S-2 Table S1: Calculated classical barrier heights (kcal/mol) for the DBH24-W4 database (The ZPE contributions are excluded.) Reactions Best Est. WMS Hydrogen Atom Transfers ! ∆E! 6.35 6.25 OH + CH4 → CH3 + H2O ! ∆E! 19.26 19.28 ! ∆E! 10.77 10.88 H + OH → O + H2 ! ∆E! 13.17
    [Show full text]
  • Photoredox Α‑Vinylation of Α‑Amino Acids and N‑Aryl Amines Adam Noble and David W
    Communication pubs.acs.org/JACS Open Access on 07/14/2015 Photoredox α‑Vinylation of α‑Amino Acids and N‑Aryl Amines Adam Noble and David W. C. MacMillan* Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States *S Supporting Information radicals to the direct synthesis of allylic amines from N-aryl ABSTRACT: A new coupling protocol has been amines or α-amino acids. Specifically, we hypothesized that allyl developed that allows the union of vinyl sulfones with amines should be accessible via exposure of α-amino radicals to photoredox-generated α-amino radicals to provide allylic olefins that can generically participate in radical-based vinylation amines of broad diversity. Direct C−H vinylations of N- mechanisms (i.e., incorporate leaving groups that are susceptible aryl tertiary amines, as well as decarboxylative vinylations to single-electron β-elimination pathways). As an overarching of N-Boc α-amino acids, proceed in high yield and with goal of this work we hoped to demonstrate that photoredox- excellent olefin geometry control. The utility of this new generated α-amino radicals provide a complementary approach allyl amine forming reaction has been demonstrated via the to allyl amine production in comparison to stoichiometric metal- syntheses of several natural products and a number of based technologies. Herein, we describe the successful execution established pharmacophores. of these ideals and present the first direct C−H vinylation of N- aryl tertiary amines and the first decarboxylative olefination of N- Boc α-amino acids using vinyl sulfones in the presence of isible light photoredox catalysis has recently emerged as a iridium-based MLCT catalysts.
    [Show full text]
  • Nature of the First Electron Transfer in Electrochemical Ammonia Activation in a Nonaqueous Medium
    Nature of the First Electron Transfer in Electrochemical Ammonia Activation in a Nonaqueous Medium The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Schiffer, Zachary et al. "Nature of the First Electron Transfer in Electrochemical Ammonia Activation in a Nonaqueous Medium." Journal of Physical Chemistry C 123, 15 (April 2019): 9713-9720 © 2019 American Chemical Society As Published http://dx.doi.org/10.1021/ACS.JPCC.9B00669 Publisher American Chemical Society (ACS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/124016 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. Nature of the First Electron Transfer in Electrochemical Ammonia Activation in a Non-Aqueous Medium Zachary J Schiffer1, Nikifar Lazouski1, Nathan Corbin1, Karthish Manthiram1,* 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA *Corresponding Author: 617-715-5740, [email protected] 1 Abstract Decreasing costs of renewable sources of electricity will increase the viability of electrochemical processes in chemical manufacturing. To this end, improved understanding of electrochemical N-H bond activation is essential to develop electrochemical routes for nitrogen-containing chemicals. In this work, we investigate electrochemical ammonia activation in acetonitrile, a prototypical non-aqueous solvent for electro-organic syntheses. Non-aqueous environments are desirable for electro- organic syntheses due to large electrochemical stability windows and high solubility for organic products. We find that ammonia oxidation in acetonitrile proceeds through an outer-sphere mechanism involving an initial electron transfer as the rate-determining step, likely producing an ammonia radical cation.
    [Show full text]
  • Photoredox Activation of Carbon Dioxide for Amino Acid Synthesis in Continuous Flow
    Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Seo, Hyowon et al. “Photoredox Activation of Carbon Dioxide for Amino Acid Synthesis in Continuous Flow.” Nature Chemistry 9, 5 (December 2016): 453–456 © 2017 Macmillan Publisher Limited part of Springer Nature As Published http://dx.doi.org/10.1038/NCHEM.2690 Publisher Nature Publishing Group Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/113316 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nat Chem Manuscript Author . Author manuscript; Manuscript Author available in PMC 2017 June 26. Published in final edited form as: Nat Chem. 2017 May ; 9(5): 453–456. doi:10.1038/nchem.2690. Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow Hyowon Seo1, Matthew H. Katcher1, and Timothy F. Jamison1,* 1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Abstract Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited its use in chemical synthesis. In particular, methods for carbon–carbon bond formation generally rely on two-electron mechanisms for CO2 activation and require highly activated reaction partners. Alternatively, radical pathways accessed via photoredox catalysis could provide new reactivity under milder conditions. Here we demonstrate the direct coupling of CO2 and amines via the single-electron reduction of CO2 for the photoredox-catalyzed, continuous flow synthesis of α- amino acids.
    [Show full text]
  • Arxiv:1510.07052V1 [Astro-Ph.EP] 23 Oct 2015 99 Lae Ta.20,Adrfrne Therein)
    A Chemical Kinetics Network for Lightning and Life in Planetary Atmospheres P. B. Rimmer1 and Ch Helling School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, United Kingdom ABSTRACT There are many open questions about prebiotic chemistry in both planetary and exoplane- tary environments. The increasing number of known exoplanets and other ultra-cool, substellar objects has propelled the desire to detect life and prebiotic chemistry outside the solar system. We present an ion-neutral chemical network constructed from scratch, Stand2015, that treats hydrogen, nitrogen, carbon and oxygen chemistry accurately within a temperature range between 100 K and 30000 K. Formation pathways for glycine and other organic molecules are included. The network is complete up to H6C2N2O3. Stand2015 is successfully tested against atmo- spheric chemistry models for HD209458b, Jupiter and the present-day Earth using a simple 1D photochemistry/diffusion code. Our results for the early Earth agree with those of Kasting (1993) for CO2, H2, CO and O2, but do not agree for water and atomic oxygen. We use the network to simulate an experiment where varied chemical initial conditions are irradiated by UV light. The result from our simulation is that more glycine is produced when more ammonia and methane is present. Very little glycine is produced in the absence of any molecular nitrogen and oxygen. This suggests that production of glycine is inhibited if a gas is too strongly reducing. Possible applications and limitations of the chemical kinetics network are also discussed. Subject headings: astrobiology — atmospheric effects — molecular processes — planetary systems 1. Introduction The input energy source and the initial chem- istry have been varied across these different ex- The potential connection between a focused periments.
    [Show full text]
  • United States Patent Office
    3,388,113 United States Patent Office Patented June 11, 1968 2 By the use of the p-nitrocarbobenzoxy radical the 3,388,113 guanidino radical also remains protected when the carbo PROTECTION OF THE GUAND NO GROUP OF tert-butoxy radical or the p-methoxycarbobenzoxy radical, ARGENNEDURING PEPTDE SYNTHESS BY THE p-NITROCARBOBENZOXY GROUP which may also be used for the protection of the a-amino Stephan Guttmann, Alischwil, Roger Boissonnas, Bott radical, or the tert-butyl radical for the protection of the mingen, and Janos Pless, Basel, Switzerland, assignors carboxyl radical, is split off by the action of trifluoro to Sandoz Ltd. (also known as Sandoz A.G.), Basel, acetic acid, as well as when the triphenylmethyl radical Switzerland is split off from the O-amino radical with aqueous acetic No Drawing. Filled Aug. 27, 1964, Ser. No. 392,624 acid and when an ester radical is saponified by the action Clains priority, application Switzerland, Aug. 30, 1963, of an aqueous alkali. The present invention is also par 10,776/63 0 ticularly surprising because it has been established that 2 Claims. (Cl. 260-12.5) N"-p-nitrobenzyloxycarbonyl-L-arginine is not suitable for the building up of polypeptides. The protective radical of the invention is also stable ABSTRACT OF THE DESCLOSURE towards all condensation methods hitherto known for the The guanidino group of arginine, arginine-containing building up of polypeptides, e.g., the azide method, the peptides and their derivatives may be protected by reac method of the mixed anhydrides, the method of the acti tion with p-nitrocarbobenzoxy chloride.
    [Show full text]
  • Photocatalytic Methods for Amino Acid Modification Cite This: Chem
    Chem Soc Rev View Article Online TUTORIAL REVIEW View Journal | View Issue Photocatalytic methods for amino acid modification Cite this: Chem. Soc. Rev.,2021, 50,39 Thomas A. King, Jiyan Mandrup Kandemir, Stephen J. Walsh and David R. Spring * Amino acid modification plays an important role across several fields, including synthetic organic chemistry, materials science, targeted drug delivery and the probing of biological function. Although a myriad of methods now exist for the modification of peptides or proteins, many of these target a handful of the most reactive proteinogenic amino acids. Photocatalysis has recently emerged as a mild approach for amino acid modification, generating a sizable toolbox of reactions capable of modifying Received 20th July 2020 almost all of the canonical amino acids. These reactions are characterised by their mild, physiologically DOI: 10.1039/d0cs00344a compatible conditions, greatly enhancing their usefulness for amino acid modification. This review aims to introduce the field of photocatalytic amino acid modification and discusses the most recent Creative Commons Attribution 3.0 Unported Licence. rsc.li/chem-soc-rev advances. Key learning points (1) Amino acids are involved across a wide range of fields, from organic synthesis to biology to materials science. (2) Side chains of amino acids provide unique properties to peptides or proteins. (3) Side chains of amino acids can be selectively targeted to enable modification of the amino acid, peptide or protein. (4) Photocatalysis uses mild conditions to facilitate modification, making it appropriate for use on biological systems. (5) Appropriate selection of photocatalyst, based on redox potentials, can enable selective modification of most amino acids.
    [Show full text]
  • Recent Developments in Cyclization Reactions of Α-Aminoalkyl Radicals
    General Papers ARKIVOC 2004 (xiv) 10-35 Recent developments in cyclization reactions of α-aminoalkyl radicals José M. Aurrecoechea* and Rubén Suero Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apartado 644, 48080 Bilbao, Spain E-mail: [email protected] (received 2 Apr 04; accepted 21 Jun 04; published on the web 28 Jun 04) Abstract The intramolecular additions of C-centered neutral α-aminoalkyl radicals onto suitably positioned C-C double bonds provide a ready access into functionalized carbocycles and heterocycles. This strategy offers considerable versatility in the selection of starting materials since a number of methods using different functional groups and reagents are available for α- aminoalkyl radical generation. This review covers the recent progress in this field. Keywords: α-Aminoalkyl radical, intramolecular radical additions, pyrrolidines, homolytic cleavage, translocation, PET, SmI2-promoted reductions Contents 1. Introduction 2. Methods for α-amino radical generation and applications 2.1 Metal hydride-mediated homolysis of C-S or C-Se bonds 2.2 Radical translocation 2.3 Photoinduced single electron transfer (PET) from α-amino silane precursors 2.4 SmI2-promoted reduction of imines and iminium cations 2.5 Radical cyclization onto enamides and imines 3. Conclusions 1. Introduction The chemistry of C-centered α-amino radicals has attracted traditionally the attention of the scientific community mainly due to their involvement in processes of biological or industrial ISSN
    [Show full text]
  • Photoredox Catalysis in Organic Chemistry Megan H
    This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Perspective pubs.acs.org/joc Photoredox Catalysis in Organic Chemistry Megan H. Shaw, Jack Twilton, and David W. C. MacMillan* Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States ABSTRACT: In recent years, photoredox catalysis has come to the forefront in organic chemistry as a powerful strategy for the activation of small molecules. In a general sense, these approaches rely on the ability of metal complexes and organic dyes to convert visible light into chemical energy by engaging in single-electron transfer with organic substrates, thereby generating reactive intermediates. In this Perspective, we highlight the unique ability of photoredox catalysis to expedite the development of completely new reaction mechanisms, with particular emphasis placed on multicatalytic strategies that enable the construction of challenging carbon−carbon and carbon− heteroatom bonds. ■ INTRODUCTION this catalytic platform to organic synthesis begun to be fully Over the last century, the discovery, development, and use of realized. A key factor in the recent yet rapid growth of this activation platform has been the recognition that readily light-mediated catalysis has enabled the invention of a wide accessible metal polypyridyl complexes and organic dyes can variety of nontraditional bond constructions in organic facilitate the conversion
    [Show full text]
  • EPR Study of Nitroxides Formed from the Reaction of Nitric Oxide with Photolyzed Amides
    __________________________________________________________________________www.paper.edu.cn MAGNETIC RESONANCE IN CHEMISTRY Magn. Reson. Chem. 2003; 41: 647–659 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1229 EPR study of nitroxides formed from the reaction of nitric oxide with photolyzed amides Fan Wang, Jing Jin and Longmin Wu∗ State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China Received 17 March 2003; Revised 12 May 2003; Accepted 13 May 2003 Free radicals generated from UV irradiation of simple aliphatic amides in anaerobic and nitric oxide (NO)-saturated liquid mixtures or solutions gave EPR spectra of nitroxides. The application of isotopic effects to EPR spectra and the generation of radicals by transient radical attack on substrate molecules or by photolysing amine or acetoin were used to help identify photochemically produced radicals from the amides. The aliphatic amides used were formamide, acetamide and their N-methyl- or deuterium- substituted derivatives. Transient radicals used to attack the amides via hydrogen-atom abstraction were generated from the initiator AIBN or AAPH. The observation of various nitroxides indicates the reactivity of NO for trapping acyl, carbamoyl and other carbon-centered radicals. Possibly mechanistic pathways diagnosed with this trap are proposed. Copyright 2003 John Wiley & Sons, Ltd. KEYWORDS: EPR; nitric oxide; nitroxide; amides; acyl; carbamoyl INTRODUCTION ‘Non-’ acyl radicals can be generated by different pro- cesses and trapped by nitroso compounds, yielding acylalkyl It has been well established that nitric oxide (NO) is a highly nitroxides.9–11 The EPR spectroscopic features of acylalkyl stable free radical under chemical conditions. NO shows no nitroxides are characterized by a significantly smaller nitro- tendency to dimerize or disproportionate.
    [Show full text]