DOCSLIB.ORG

Implications for the Organic Chemistry of Sulfur

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Implications for the Organic Chemistry of Sulfur The Organosulfur Chemistry of the Genus AZZium - Implications for the Organic Chemistry of Sulfur By Eric Block” A Cook’s tour is presented of the organosulfur chemistry of the genus Allium, as represented, inter alia, by garlic (Allium sativum L.) and onion (Allium cepa L.). We report on the biosyn- thesis of the S-alk(en)yl-L-cysteineS-oxides (aroma and flavor precursors) in intact plants and on how upon cutting or crushing the plants these precursors are cleaved by allinase enzymes, giving sulfenic acids-highly reactive organosulfur intermediates. In garlic, 2-propenesulfenic acid gives allicin, a thiosulfinate with antibiotic properties, while in onion I-propenesulfenic acid rearranges to the sulfine (2)-propanethial S-oxide, the lachrymatory factor (LF) of onion. Highlights of onion chemistry include the assignment of stereochemistry to the LF and determination of the mechanism of its dimerization; the isolation, characterization, and syn- thesis of thiosulfinates which most closely duplicate the taste and aroma of the freshly cut bulb, and additional unusual compounds such as zwiebelanes (dithiabicyclo(2.1.llhexanes), a bis- sulfine (a 1,4-butanedithial S,Y-dioxide), antithrombotic and antiasthmatic cepaenes (a- sulfinyl disulfides), and vic-disulfoxides. Especially noteworthy in the chemistry of garlic are the discovery of ajoene, a potent antithrombotic agent from garlic, and the elucidation of the unique sequence of reactions that occur when diallyl disulfide, which is present in steam-dis- tilled garlic oil, is heated. Reaction mechanisms under discussion include [3,3]-and [2,3]-sigma- tropic rearrangements involving sulfur (e.g. sulfoxide-accelerated thio- and dithio-Claisen rearrangements) and cycloadditions involving thiocarbonyl systems. In view of the culinary importance of alliaceous plants as well as the unique history of their use in folk medicine, this survey concludes with a discussion of the physiological activity of the components of these plants: cancer prevention, antimicrobial activity, insect and animal attractive/repulsive activ- ity, olfactory-gustatory-lachrymatory properties, effect on lipid metabolism, platelet aggrega- tion inhibitory activity and properties associated with ajoene. And naturally, comments about onion and garlic induced bad breath and heartburn may not be overlooked. 1. Introduction counterpart in the complex chemistry of this and other allia- ceous plants, representing a microcosm of the field of We remember the fish which we did eat in Egypt, organosulfur chemistry. More specifically, Allium chemistry the cucumbers, melons, leeks, onions and garlic! presents us with examples of sulfur compounds with striking Num. 11 :4-6 physiological activity as well as culinary appeal, reactive organosulfur intermediates with unusual bonding, challeng- What is more familiar and pleasant to the senses than ing analytical problems, compounds with chirality at sulfur freshly chopped or sauted garlic, sliced or boiled onions, and other stereochemical features related to the presence of steaming leeks, finely diced chives, crisp raw scallions, or the sulfur, novel organosulfur heterocycles with notable spectro- delicate shallot? The scents of these commonplace plants scopic properties, redox reactions involving sulfur, as well as brings back memories of mother’s kitchen, a favorite restau- processes involving sulfur radicals, sulfur stabilized carbo- rant or even a walk through a meadow rich with the aroma cations, pericyclic reactions, noteworthy rearrangements, of wild onions. The adjectives applied to these plants, zesty, and reactions of utility in synthetic organic chemistry.“] lusty, assertive, piquant, and distinctive, and even the botan- For twenty-five years I have been exploring the organosul- ical name Allium, derived from the Celtic word “all”, which fur chemistry of the genus Allium, as represented by garlic means pungent, betray the presence of a host of remarkable (Allium sativum L.), onion (Allium cepa L.), leek (Allium flavorants and odorants all having in common one element, ampeloprasum L. var. porrum), scallion (Allium fistulosum), sulfur. Many of these flavorful sulfur compounds contain shallot (Allium ascalonicum auct.), great-headed (“ele- the ally1 group, which in turn gets its name from Allium. It phant”) garlic (Allium ainpeloprasum L. var. holmense), wild is the presence of these organosulfur compounds, more than garlic (Allium ursinum), chive (Allium schoenoprasum L.), any other attribute, that defines the character of this extraor- and Chinese chive (Allium tuberosum L.) (Fig. 1). When I dinary genus. The great American poet Carl Sanburg said: began this study, much outstanding research had already “Life itself is like an onion; it has a bewildering number of been done in this area, e.g. as summarized in a review article layers. You peel them ofJ one by one, and sometimes you cry. I’ by Nobel Laureate Arturi Virtanen.[’I As my research pro- The “bewildering number of layers” of the onion has its ceeded it became clear that there were still significant puzzles remaining to be solved, that these most common plants [“I Professor E. Block could teach us much about sulfur chemistry, and that the Department of Chemistry State University of New York at Albany compounds and mixtures produced when these plants are cut Albany, NY 12222 (USA) display an even broader range of biological activities than Angenz. Chem. Int. Ed. Ennl. 1992, 3f,1135-1178 0 VCH Verlagsgeselischafi mbH, W-6940 Weinheim, 1992 0570-0833/92/0909-1135 $3.50+ .25/0 1135 earlier suspected. While extracts and potions of garlic and ity could be demonstrated by addition of water to the insol- onion have been used for millennia in folk medicine, com- uble residue. When, however, a small quantity (1 mgmL-’) mercial products derived from these plants are now enjoying of fresh garlic powder was added to the alcohol insoluble growing popular use in many countries. Furthermore, re- fraction in water (20 mgmL-‘), the activity of the treated sponding to epidemiological evidence that lower cancer risks sample was shown to be equal to that of the original untreat- are associated with increased consumption of alliaceous ed powder. The 95 % ethanol treatment has inactivated the plants, health organizations have recently targeted garlic and enzyme required for cleavage of the precursor and addition onion as prime candidates for “designer foods” programs, of a small quantity of fresh enzyme brought about the usual programs to develop new foods that will help prevent cells cleavage. from becoming cancerous. For all of these reasons a detailed Since a strict definition of “essential oil” is “a volatile exploration of the organosulfur chemistry of the genus Alli- substance contained in certain aromatic plants that imparts um seemed justified as well as timely. This review summa- distinctive odor to the plant” and since the volatile sub- rizes progress in this field both in my own and other labora- stances of the Allium spp. are not found in the plant but torie~.[~’ result from disrupting the plant cells, it is preferable to de- scribe the process leading to a particular Allium-derived product, e.g. “steam volatile components” or “head space vo~ati~es”.[’~ 2. Organosulfur Compounds of Intact Plants Well loved he garleek, oynons, and eek lekes, 2.1. Sulfur Amino Acids Secondary Metabolites and for to drynken strong wyn, reed as blood. in Alliurn spp. “Canterbury Tales” Geoffrey Chaucer (1342-1400) Let onion atoms lurk within the bowl and, scarce suspected, animate the whole. The earliest reports concerning the isolation of organic “Recipe for Salad”, compounds from garlic (1844,1892) and onion by Wertheim Sydney Smith (1771-1845) (1844) and Semmler (1892) in Germany identified diallyl sulfidet4] (corrected in 1892 to the dis~lfide[~])and a Garlic, onion and other members of the Allium spp. con- propenyl propyl dis~lfide[~]as the principal components of tain I - 5 % dry weight of nonprotein sulfur amino acid sec- the distilled oils (“atherische Ole’’) of garlic and onion, re- ondary metabolites. Pioneering studies in the 1940s by Stoll spectively. In the 1940s it became apparent that these and and Seebeck in Basel demonstrated that the stable precursor other volatile sulfur compounds were secondary compounds of Cavallito’s antibacterial principle of garlic 1 is (+)-S-2- formed by enzymatic action on precursors in the intact bulb. propenyl-L-cysteine S-oxide (2, ‘‘alliin”).[81In the intact cell, Thus, in 1945, Cavallito et al. in Rennselaer, New York, re- 2 and related S-alk(en)yl-L-cysteineS-oxides (aroma and fla- ported that when garlic cloves were frozen in dry ice, pulver- vor precursors) are located in the cytoplasm and the C-S ized, and extracted with acetone, “the acetone extracts upon lyase enzyme allinase in the vacuole.[g1Disruption of the cell evaporation yielded only minute quantities of residue and no results in release of allinase and subsequent a$-elimination sulfides, indicating the absence of free sulfides in the plant. of the S-oxides, ultimately affording volatile and odorous The [white] garlic powder had practically no odor, but upon low molecular weight organosulfur compounds such as 1 addition of small quantities of water, the typical odor was (Scheme I). Four sulfoxides occur in Allium spp.: S-2- detected and the antibacterial principle (1) could be extract- propenyl-, S-(E)-1-propenyl-, S-methyl- and S-propyl-L- ed and isolated. This demonstrates that neither 1 nor the ally1 cysteine S-oxides (2,5-7 respectively). Onions contain 5-7 sulfides found in “Essential Oil of Garlic” are present as such while garlic contains 2, 5, and 6.[10-131The distinctive fla- in whole garlic. When the powder was heated to reflux for vors of the various Allium spp. reflect the varying amounts thirty minutes with a small volume of 95 YOethanol, no activ- of compounds 2,5-7, particularly of 5 (“isoalliin”), which is Eric Block, born in 1942 in New York City, studied chemistry at Queens College of the City University of New York. He received his Ph.D.
Load more

Recommended publications
  • Allium Discoloration: the Nature of Onion Pinking and Garlic Greening
    Czech J. Food Sci. Vol. 22, Special Issue Allium Discoloration: The Nature of Onion Pinking and Garlic Greening R. KUBEC1*, M. HRBÁČOVÁ1, R. A. MUSAH2 and J. VELÍŠEK1 1Department of Food Chemistry and Analysis, Institute of Chemical Technology, Prague, Czech Republic, *E-mail: [email protected]; 2Department of Chemistry, SUNY Albany, Albany, NY, USA Abstract: Precursors involved in the formation of pink and green-blue pigments during onion and garlic process- ing, respectively, have been studied. It has been confirmed that the formation of both pigments is of a very similar nature, with (E)-S-(1-propenyl)cysteine sulfoxide (isoalliin) serving as the primary precursor. Upon disruption of the tissue, isoalliin and other S-alk(en)ylcysteine sulfoxides are enzymatically cleaved, yielding prop-1-enyl- containing thiosulfinates [CH3CH = CHS(O)SR; R = methyl, allyl, propyl, 1-propenyl], among others. The latter compounds subsequently react with amino acids to produce the pigments. Whereas the onion and leek-related propyl, prop-1-enyl and methyl derivatives can form pink, pink-red and magenta compounds, those containing the allyl group yield dark blue products after reacting with glycine at pH 5.0. Keywords: Allium; garlic; onion; discoloration; pigment INTRODUCTION sulfoxide (isoalliin, 1). Isoalliin is the major free amino acid occurring in onion and it is also present During processing of garlic (Allium sativum L.), as a minor S-substituted cysteine sulfoxide deriva- onion (A. cepa L.) and leek (A. porrum L.) intensely tive in garlic. The key role of isoalliin in the dis- colored pigments are often formed. In the case of coloration of garlic was later confirmed by L���� garlic, green, blue-green or blue compounds are [5].
    [Show full text]
  • A Study of the Thermal Stability of Benzyl 2,4-Dimethyl-6
    A STUDY OF THE THERMAL STABILITY OF BENZYL 2 1 4·DIMETHYL•6•PROPENYLPEENYL ETHER by RONALD JENE DUPZIK A THESIS submitted to OREGON STATE COLLEGE in partial fulfillment ot the requirements tor the degree ot MASTER OF SCIENCE June 1958 APPEOYED I Redacted for Privacy tarogl,rtr Frofrlter of 0rnt In 0hrrgr of, I{aJor Redacted for Privacy Chrlrnen of Drprntmat of Shontrtrf Redacted for Privacy Ghelrura of Bahool &adurtc 0omlttm Redacted for Privacy Deur of 0mdu*tr $rhoel Drtc thrrtr lr prrrontrd Ausust 7, 1957 Sypcd by l{*y ldrnr 'l'o M;y Mothez­ in memory ot My Father ACKNOWLEDGMENT The author wishes to expreaa hia apprecia­ tion to Dr. Elliot N. Marvell whose help and guidance has made this work possible. Thanks are given to Dr. B. E. Christensen and Dr . c. s. Pease who have so graciously helped in Dr. Marvell's absence. To Miss Isabelle Forbusoh for her patience and help in the preparation of this manuscript. And, to the Martinez Research Laboratory ot the Shell Oil Company for the infrared and ultraviolet spectral analysis of the new compounds. TABLE OF CONTENTS Pa!e INTRODUCTION • • • • • • • • • • • • • • • • • • 1 HISTORICAL • • • • • • • • • • • . •. • • • • • • 3 DISCUSSION • • • • • • • • • • • • • • • • • • • • 16 EXPERIMENTAL • • • • • • • • • • • • • • • • • • 29 Synthesis A • • • • • • 29 Synthesis B • • • • • • • • • • • • • • • 31 Rearrangement and Thermal Stability • • • • • 37 SUMMARY. • • • • • • • • • • • • • 40 BI BLIOGRAPHY • • • • • • • • • • • • • • • • • • • 41 LIST OF FIGURES Figure 1 • • • " • • • • • • • • • •
    [Show full text]
  • TRU President Alan Shaver, List of Publications
    Alan Shaver President and Vice-Chancellor of Thompson Rivers University PUBLICATIONS 127. A. Shaver, B. El-Mouatassim, F. Mortini and F. Belanger-Gariepy, “The Reactions of η5- 5 C5Me5Ir(PMe3)(SH)2 and η -C5Me5Ir(PMe3)(SH)(H) with Thionylaniline (PhNSO) to give Novel S3O and S2O-Iridium complexes” Organometallics 26, 4229-4233 (2007) 126. A.Z. Rys, A.-M. Lebuis, A. Shaver and D.N. Harpp, “Rearrangement of Molybdocene tetraoxide + Cp2MoS4O4 to Give (Cp2MoS2H)2 : A Novel Hydrogen-bond Stabilized Molybdocene Disulfide Dimer”, Inorg. Chem. 45, 341-344 (2006) 124. I. Kovacs, F. Belanger-Gariepy and A. Shaver, “Synthesis and Characterization of the First Mononuclear Iron Silanethiolate Complexes Containing an Unsupported Fe-S-Si Bond System. X-Ray Crystal Structure of CpFe(CO)2SSiPh3 and Its Reaction with SO2”, Inorg. Chem.42, 2988-2991 (2003). 123. Y. Song, I.S. Butler and A. Shaver, “High Pressure Vibrational Study of the Catalyst Candidate cis- dimercaptobis(triphenylphosphine)platinum(II), cis-[(Ph3P)2Pt(SH)2]”, Spectrochimica Acta A 58, 2581- 2587 (2002). 122. A.Z. Rys, A.-M. Lebuis, A. Shaver and D.N. Harpp, “Insertion of SO2 into the S-S Bond of Cp2MoS2 and Cp2MoS2O to give Molybdocene Dithiosulfates and Bis(O-alkylthiosulfate), Respectively”, Inorg. Chem. 41, 3653-3655 (2002). 121. B. El-Mouatassim, C. Pearson and A. Shaver, “Modeling Claus-like Chemistry: The Preparation of Cp*Ir(PMe3)S4 from Cp*Ir(PMe3)(SH)2 and SO2”, Inorg. Chem. 40, 5290-5291 (2001).. 120. A. Shaver, M. El-khateeb and A.-M. Lebuis, “Insertion Reactions of (PPh3)2Pt(SR)2 with CS2, where R = H, CMe3, CHMe3, 4-C6H4Me; the Structure of (PPh3)Pt(S-4-C6H4Me)(S2CS-4-C6H4Me)”, Inorg.
    [Show full text]
  • Proceedings of the Indiana Academy of Science
    The Structure of the Stereoisomeric Trithianes 1 E. Capaigne and Walter M. Budded, Indiana University When acetaldehyde is treated with hydrogen sulfide and hydrogen chloride, trithioacetaldehyde is formed, and originally (1) three different isomers; a, m.p. 101°; /3; m.p. 125-6°, and 7; m.p. 81°; were isolated. It was possible to convert a into p by heating with iodine or acetyl chloride. Since the trithiane ring was assumed to be planar, only two isomers, cis-cis (I) and cis-trans (II) should exist. Suyver (2) demon- strated that a eutectic mixture of 60% a and 40% p isomer melts sharply at 75-76° and it was generally conceded that this is the explana- tion of the 7-isomer. It is still reported in the handbooks, however, and crops up as justification for different structures of the trithiane ring. In 1947, Schonberg and Barakat (3), disturbed by the ready interchange of a to jS forms in a cylic system in which tautomerism is presumably impossible, proposed the following theory: "The three carbon atoms and the three sulfur atoms in 1, 3, 5- trithiane molecules do not lie in one plane, but may be regarded as 'boat' and 'chair' structures, the interconversion then being readily explained. According to this explanation, the a- and /3-forms of trithioacetaldehyde, for example, are either both cis- or both trans- forms; the isomeric change is due to a change of 'boat' into 'chair' structures, or vice versa. This new theory demands a greater number of isomers than have, so far, been isolated, but it is not thereby neces- sarily invalidated, for some isomers (7-forms) have occasionally been described, which have been attributed inter alia to polymorphism or the occurrence of eutectic mixtures.
    [Show full text]
  • Rising Importance of Organosulfur Species for Aerosol Properties and Future 2 Air Quality
    1 Rising Importance of Organosulfur Species for Aerosol Properties and Future 2 Air Quality 3 M. Riva1,#,¥,*, Y. Chen1,¥, Y. Zhang1,2, Z. Lei3, N. E. Olson4, H. C. Boyer Chelmo5, S. Narayan5, 4 L. D. Yee6, H. S. Green1,‡, T. Cui1, Z. Zhang1, K. Baumann7, M. Fort7, E. Edgerton7, S. H. 5 Budisulistiorini1,†, C. A. Rose1, I. O. Ribeiro8, R. L. e Oliveira8, E. O. dos Santos9, C. M. D. 6 Machado9, S. Szopa10, Y. Zhao11,§, E. G. Alves12, S. S. de Sá13, W. Hu14, E. M. Knipping15, S. L. 7 Shaw16, S. Duvoisin Junior8, R. A. F. de Souza8, B.B. Palm,14 J. L. Jimenez14, M. Glasius17, A. 8 H. Goldstein6, H. O. T. Pye1,18, A. Gold1, B. J. Turpin1, W. Vizuete1, S. T. Martin13,19, J. A. 10 5 3,4* 1* 9 Thornton , C. S. Dutcher , A. P. Ault , and J. D. Surratt 10 Affiliations: 11 1 Department of Environmental Sciences and Engineering, Gillings School of Global Public 12 Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 13 2 Aerodyne Research Inc., Billerica, MA, USA. 14 3 Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA. 15 4 Department of Chemistry, University of Michigan, Ann Arbor, MI, USA. 16 5 Department of Mechanical Engineering, University of Minnesota-Twin Cities, Minneapolis, 17 MN, USA. 18 6 Department of Environmental Science, Policy, and Management, University of California, 19 Berkeley, CA, USA. 20 7 Atmospheric Research & Analysis, Inc., Cary, NC, USA. 21 8 Escola Superior de Tecnologia, Universidade do Estado do Amazonas, Manaus, Amazonas, 22 Brasil.
    [Show full text]
  • Allicin in Blood.Pdf
    European Journal of Medicinal Chemistry 45 (2010) 1912–1918 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech Original article Reaction mechanisms of allicin and allyl-mixed disulfides with proteins and small thiol molecules Talia Miron a,*, Irving Listowsky b, Meir Wilchek a a Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel b Department of Biochemistry, Albert-Einstein College of Medicine, Bronx, NY, USA article info abstract Article history: Allylsulfides from garlic are chemopreventive agents. Entering cells they are expected to initially interact Received 15 October 2009 with glutathione. Accordingly, reaction mechanisms of the product, S-allylthio-glutathione, with model Received in revised form proteins and thiols were analyzed in cell free systems. With glutathionyl, cysteinyl or captopril repre- 14 January 2010 senting S-allyl aliphatic adducts, the reaction with sulfhydryl groups resulted in mixed disulfide Accepted 15 January 2010 mixtures, formed by both, S-allyl and aliphatic moieties. Available online 21 January 2010 To improve conventional prodrug treatment of blood pressure, cancer and intestinal inflammation S-allylthio prodrugs, such as S-allylthio-6-mercaptopurine and S-allylthio-captopril were synthesized. Keywords: Allicin Synergistic activities of the 2 constituents, as well as increased cell permeability allow for efficient in vivo Glutathione activity. Upon reaction of these derivatives with glutathione, S-allylthio-glutathione is formed, while S-Allylthio-mixed disulfide 6-mercaptopurine is the leaving group. Excess cellular glutathione enables several cycles of sulfhydryl- Prodrug disulfide exchange reactions to occur, extending the hybrid drug’s pharmacodynamics. Mechanism of action Ó 2010 Elsevier Masson SAS.
    [Show full text]
  • Unit One Part 2: Naming and Functional Groups
    gjr-–- 1 Unit One Part 2: naming and functional groups • To write and interpret IUPAC names for small, simple molecules • Identify some common functional groups found in organic molecules O CH3 H3C N H N O N N O H3C S N O N H3C viagra™ (trade name) sildenafil (trivial name) 5-(2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl)-1-methyl-3-propyl-1H- pyrazolo[4,3-d] pyrimidin-7(6H)-one dr gareth rowlands; [email protected]; science tower a4.12 http://www.massey.ac.nz/~gjrowlan gjr-–- 2 Systematic (IUPAC) naming PREFIX PARENT SUFFIX substituents / minor number of C principal functional functional groups AND multiple bond group index • Comprises of three main parts • Note: multiple bond index is always incorporated in parent section No. Carbons Root No. Carbons Root Multiple-bond 1 meth 6 hex Bond index 2 eth 7 hept C–C an(e) 3 prop 8 oct C=C en(e) 4 but 9 non C≡C yn(e) 5 pent 10 dec gjr-–- 3 Systematic (IUPAC) naming: functional groups Functional group Structure Suffix Prefix General form O –oic acid acid –carboxylic acid carboxy R-COOH R OH O O –oic anhydride anhydride –carboxylic anhydride R-C(O)OC(O)-R R O R O –oyl chloride acyl chloride -carbonyl chloride chlorocarbonyl R-COCl R Cl O –oate ester –carboxylate alkoxycarbonyl R-COOR R OR O –amide amide –carboxamide carbamoyl R-CONH2 R NH2 nitrile R N –nitrile cyano R-C≡N O –al aldehyde –carbaldehyde oxo R-CHO R H O ketone –one oxo R-CO-R R R alcohol R OH –ol hydroxy R-OH amine R NH2 –amine amino R-NH2 O ether R R –ether alkoxy R-O-R alkyl bromide bromo R-Br (alkyl halide) R Br (halo) (R-X) gjr-–- 4 Nomenclature rules 1.
    [Show full text]
  • Polymeric Reagents with Propane-1,3-Dithiol Functions and Their Precursors for Supported Organic Syntheses
    J. Org. Chem. 2000, 65, 4839-4842 4839 Polymeric Reagents with Propane-1,3-dithiol Functions and Their Precursors for Supported Organic Syntheses Vincenzo Bertini,*,† Francesco Lucchesini,† Marco Pocci,† and Angela De Munno‡ Dipartimento di Chimica e Tecnologie Farmaceutiche ed Alimentari, Universita´ di Genova, Via Brigata Salerno, I-16147 Genova, Italy, and Dipartimento di Chimica e Chimica Industriale, Universita´ di Pisa, Via Risorgimento, 35, I-56126 Pisa, Italy [email protected] Received January 19, 2000 Reliable completely odorless syntheses of soluble copolymeric reagents of styrene type containing propane-1,3-dithiol functions able to convert carbonyl compounds into 1,3-dithiane derivatives and to support other useful transformations are reported together with their progenitor copolymers containing benzenesulfonate or thioacetate groups perfectly stable in open air and suitable for unlimited storage. The effectiveness of the prepared reagents as tools for polymer-supported syntheses to produce ketones by aldehyde umpolung and alkylation is tested in the conversion of benzaldehyde to phenyl n-hexyl ketone starting from copolymers with different contents of active units and molecular weights. To facilitate the adaptation of the prepared soluble copolymeric reagents to other possible applications, a table of solvents and nonsolvents is presented. Introduction Scheme 1 Recently we have reported in a preliminary com- munication1 how to harness the great synthetic potenti- alities of thioacetals and thioketals by preparing, with a completely odorless synthesis, polymeric reagents2,3 of styrene type containing propane-1,3-dithiol functions effective in producing ketones by aldehyde umpolung and alkylation after the formation of 1,3-dithiane derivatives. Such polymeric reagents were obtained through a pro- cedure based on the use of the difunctional monomer 1 prepared from commercial 4-vinylbenzyl chloride (Scheme 1), its copolymerization with styrene, and chemical modification of its copolymers.
    [Show full text]
  • WIIINIPEG, I{ANI1.Oba October 1971
    THE UNTVERSITY OF FJAI,TTTOBA STTIDIES ON TSOTHTÁ.ZOIIU}.I SÂLTS AND REIATED CO},IPOUI{DS by GART ED}¡ARD BACIIERS A T}MSIS SIMÌ,1TTTED TO TI{E FACULTY OF GR]I.DUÀTE STIIDIES ÏN PIIRÎI/iL FULIi'TIJ'&Til'r OF TI# REQUTREI.Tiü{TS TÇR TI.III DEGREE I'IÂSTER 0F SCIEÎIICE DEPARTI'ÎE]VT 0F CI{EI,IISTRY WIIINIPEG, I{ANI1.oBA October 1971 üF fi "*i¡l,''ÉËR$$iY LT BRARY ACIOTOIILEDGH,ÍTÍüTS : The research degcribed in thís thesis has been undertaken at tho suggestion of Dr. D. Id. McKínnon, for v¡hose guidance, advice, æd ass*stance ï exprees r¡\y sincere appreciation" My gratitud.e ie also due the National Research CounciÌ of Canada for the scholarships provid.ed. d.uring the course of this research, and the University of }ianitoba for the provisíon of laboratory facilities. Finally, I should like to thank rny colleaguee, I'fiss Sheena Loosmore, Ivlr. Joe Buchsbriber, Iilr. Pat Ma, a¡rd. Mr. Jack Wong. Their forbearance during several unusually od.or-ous experiments was admirable. 11 TA3I,E 0F.coNTlNTS ABSTRACT.......... o.. ó..... o. ...:. r. o õ i.. o.... o.......iii INTRODUCTION Ggngial.. - - . ô. :.' ..... o. ... .. .. .. .. r. .. o. .. .... 1 fsothiazoles. o r . c o. o . ... .. o. ¡. 2 ' I s o thi azo 1 um s s i al t . c . o . c . , . , . , o . ! 4-rsothiazoline-3-thiones... o... ô........ o.... r........ 13 . 3-Isothiazoline-l-thiones....o.....,r........er........18 Thiothiophthenes and an aza arialogue.. o...... c o. o... .,.19 DISCUSSION Purpose of resgarch...... c.. o...^... r.............. o., o..2J Reaction of isothiazolium salts ç¡ittr sutf:p¡ ¡ o o.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0220346A1 Heller Et Al
    US 20140220346A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0220346A1 Heller et al. (43) Pub. Date: Aug. 7, 2014 (54) MODULAR POLYMER HYDROGEL (22) Filed: Dec. 4, 2013 NANOPARTICLES AND METHODS OF THER MANUFACTURE Related U.S. Application Data (60) Provisional application No. 61/733,366, filed on Dec. (71) Applicants: Memorial Sloan-Kettering Cancer 4, 2012. Center, New York, NY (US); Massachusetts Institute of Technology, Publication Classification Cambridge, MA (US) (51) Int. Cl. (72) Inventors: Daniel A. Heller, New York, NY (US); A647/48 (2006.01) Jasmine Wallas, New York, NY (US); A614.9/00 (2006.01) Yair Levi, Cambridge, MA (US); (52) U.S. Cl. George W. Pratt, Waban, MA (US); CPC ......... A61K 47/4823 (2013.01); A61K 49/0054 Daniel G. Anderson, Sudbury, MA (2013.01); A61K 49/0073 (2013.01) (US); Robert Langer, Newton, MA USPC .............................. 428/402:536/51:536/112 (US) (57) ABSTRACT (73) Assignees: Memorial Sloan-Kettering Cancer In certain embodiments, a nano-sized vehicle (e.g., a nanogel Center, New York, NY (US); comprising nanoparticles) is provided herein for drug deliv Massachusetts Institute of Technology, ery with tunable biodistribution, low toxicity, and degradabil Cambridge, MA (US) ity, and with demonstrated targeting to bone. The composi tion is useful, for example, in the treatment of bone disease, particularly bone metastases from cancers such as breast, (21) Appl. No.: 14/097,212 prostate, or lung cancer. Patent Application Publication Aug. 7, 2014 Sheet 1 of 36 US 2014/0220346 A1 N Patent Application Publication Aug. 7, 2014 Sheet 2 of 36 US 2014/0220346 A1 8],'04- Patent Application Publication Aug.
    [Show full text]
  • Mechanism and Selectivity of Rhodium-Catalyzed 1:2 Coupling Of
    Article pubs.acs.org/JACS Terms of Use Mechanism and Selectivity of Rhodium-Catalyzed 1:2 Coupling of Aldehydes and Allenes Genping Huang, Marcin Kalek, and Fahmi Himo* Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden *S Supporting Information ABSTRACT: The rhodium-catalyzed highly regioselective 1:2 coupling of aldehydes and allenes was investigated by means of density functional theory calculations. Full free energy profiles were calculated, and several possible reaction pathways were evaluated. It is shown that the energetically most plausible catalytic cycle is initiated by oxidative coupling of the two allenes, which was found to be the rate-determining step of the overall reaction. Importantly, Rh−allyl complexes that are able to adopt both η3 and η1 configurations were identified as key intermediates present throughout the catalytic cycle with profound implications for the selectivity of the reaction. The calculations reproduced and rationalized the experimentally observed selectivities and provided an explanation for the remarkable alteration in the product distribution when the catalyst precursor is changed from [RhCl(nbd)]2 (nbd = norbornadiene) to complexes containing noncoordinating counterions ([Rh(cod)2X]; X = OTf, BF4,PF6; cod = 1,5-cyclooctadiene). It turns out that the overall selectivity of the reaction is controlled by a combination of the inherent selectivities of several of the elementary steps and that both the mechanism and the nature of the selectivity-determining steps change when the catalyst is changed. 1. INTRODUCTION comes from the laboratory of Murakami and consists of a 1:2 6 Rhodium(I) complexes are well-established catalysts for three- coupling of aldehydes and allenes (Scheme 2b).
    [Show full text]
  • Selected Reactions of Thiocarbonyl Compounds Oac O Ncy Oac CN 2 Shyam Krishnan Me Meo Monday, June 12, 2006 Me H Me N O H 8 P.M
    OH S Me S O O N SEt TBSO Ph O Me Me N OH BnO S Selected Reactions of Thiocarbonyl Compounds OAc O NCy OAc CN 2 Shyam Krishnan Me MeO Monday, June 12, 2006 Me H Me N O H 8 p.m. N O Me 147 Noyes H O O O HN O H H S Me S S H H BnO BnO N N i) ICH2CO2Et, CHCl3 S ii) PPh , DABCO, 3 CO2Et CHCl3, reflux (92% yield) I I OMe OMe Selected Reactions of Thiocarbonyl Compounds 1) Thiocarbonyl compounds: nomenclature and structural properties 2) Methods of Synthesis 3) Reactions of thiocarbonyl compounds and their application in the synthesis of functionalized molecules 1) Reactions of carbanions derived from Thiocarbonyl compounds. 2) Carbanion addition to the thiocarbonyl group. 3) Reactions with electrophiles - the Eschenmoser sulfide contraction. 4) Radical mediated reactions. 5) [3,3] sigmatropic rearrangements - the thio-Claisen rearrangement. 6) [4+2] cycloaddition reactions. 7) [3+2] Dipolar cycloadditions. 8) Summary and future directions. Reviews: General review: Metzner, P. Top. Curr. Chem. 1999, 204, 127. General review: Metzner, P. Synthesis 1992, 1185. Synthesis of heterocycles: Jagodzinski, T.S. Chem. Rev. 2003, 103, 197. Radical chemistry: Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413. Photochemistry: Coyle, J. D. Tetrahedron 1985, 41, 5393. Thiocarbonyl Compounds Structures, Nomenclature and Stability Thiocarbonyl compounds possess a carbon-sulfur double bond Thiocarbonyl compounds with at least one organic group bound to the thiocarbonyl carbon: O S S S S S S R H R R' R OR R NR2 R SR R R' Thioaldehyde Thioketone Thionoester Thioamide Dithioester Sulfine/Thiocarbonyl oxide Typically display greater reactivity than their carbonyl (oxygen) analogs • Larger covalent radius of sulfur vs oxygen (104.9 nm vs 70.2 nm), less efficient overlap in S3p-C2p π-bond • Dissociation energy of C=S (115 kcal/mol) is significantly lower than for C=O (162 kcal/mol).
    [Show full text]