Co-reporter:Frederic Wagner;Klaus Harms
European Journal of Organic Chemistry 2017 Volume 2017(Issue 47) pp:7107-7121
Publication Date(Web):2017/12/22
DOI:10.1002/ejoc.201701540
The use of cross-coupling reactions for the synthesis of methylene-bridged bisnaphthalenes bearing two nitro groups on one naphthalene and two amino groups on the other has been investigated. A Hauser–Heck reaction was used to prepare the substituted naphthalene building blocks. It was not possible to install a transmetallating function in the benzylic position due to side reactions with the nitro and the amino groups. A successful Suzuki reaction was achieved by using naphthyl trifluoroborates and bromomethyl naphthalenes. The resulting dinaphthyl methanes could be useful for the synthesis of push–pull substituted pentacenes.
Co-reporter:Paul Nikodemiak
Advanced Synthesis & Catalysis 2017 Volume 359(Issue 10) pp:1708-1716
Publication Date(Web):2017/05/17
DOI:10.1002/adsc.201601378
AbstractThe metal-catalyzed cycloaddition of silyl nitronates and nitriles leading to 1,2,4-oxadiazoles is described. Silver(I) triflate (AgOTf) and and ytterbium(III) triflate [Yb(OTf)3] are suitable catalysts. A variety of functional groups is tolerated in the nitrile. The reaction works well for alkenyl and aryl silyl nitronates while the use of alkyl silyl nitronates is less efficient. Mechanistic studies are in favour of an elimination of tert-butyl(dimethyl)silanol (TBSOH) after the cycloaddition step. The new approach has also been applied for the synthesis of the drug ataluren.
Co-reporter:Niels Münster, Paul Nikodemiak, and Ulrich Koert
Organic Letters 2016 Volume 18(Issue 17) pp:4296-4299
Publication Date(Web):August 18, 2016
DOI:10.1021/acs.orglett.6b02048
Ethynylcyclooctynes and diazides were synthesized and applied for a chemoselective sequence of copper(I)-catalyzed azide–alkyne cycloadditions and strain-promoted azide–alkyne cycloadditions. Chemoselectivity within the reaction sequence was achieved by balancing three factors: Cu-catalysis/ring strain/steric shielding. A cholic acid derived triazide was subjected to the cycloaddition sequence as a model system for a layer-by-layer synthesis on surfaces.
Co-reporter:Michel Fischer, Klaus Harms, and Ulrich Koert
Organic Letters 2016 Volume 18(Issue 21) pp:5692-5695
Publication Date(Web):October 18, 2016
DOI:10.1021/acs.orglett.6b02922
An efficient stereoselective synthetic approach to 7–20 oxa-bridged abietane type natural products is reported. Key steps are an asymmetric Mukaiyama aldol addition to construct the C3 stereocenter and an intramolecular organocatalyzed Stetter-type Michael addition followed by a Tishchenko reaction. An intramolecular lactone–enolate arylation delivers the tetracyclic skeleton. This synthetic strategy was applied for the first total synthesis of (+)-elevenol, an antihepatitis C active compound from Fluegga virosa, and the first total synthesis of (+)-przewalskin.
Co-reporter:Marcel Reutzel, Niels Münster, Marcus A. Lipponer, Christian Länger, Ulrich Höfer, Ulrich Koert, and Michael Dürr
The Journal of Physical Chemistry C 2016 Volume 120(Issue 46) pp:26284-26289
Publication Date(Web):September 15, 2016
DOI:10.1021/acs.jpcc.6b07501
Controlled organic functionalization of silicon surfaces as an integral part of semiconductor technology offers new perspectives for a wide range of applications. The high reactivity of the silicon dangling bonds, however, presents a major hindrance for the first basic reaction step of such a functionalization, that is, the chemoselective attachment of bifunctional organic molecules on the pristine silicon surface. We overcome this problem by employing cyclooctyne as the major building block of our strategy. Functionalized cyclooctynes are shown to react on Si(001) selectively via the strained cyclooctyne triple bond while leaving the side groups intact. The achieved selectivity originates from the distinctly different adsorption dynamics of the separate functionalities: A direct adsorption pathway is demonstrated for cyclooctyne as opposed to the vast majority of other organic functional groups. The latter ones react on Si(001) via a metastable intermediate, which makes them effectively unreactive in competition with the direct pathway of cyclooctyne’s strained triple bond.
Co-reporter:Frederic Wagner, Klaus Harms, and Ulrich Koert
Organic Letters 2015 Volume 17(Issue 22) pp:5670-5673
Publication Date(Web):November 4, 2015
DOI:10.1021/acs.orglett.5b02952
γ-Aryl-β-ketoesters can be prepared in one step from aryl bromides and bis(trimethylsilyl) enol ethers using catalytic amounts of Pd(dba)2/t-Bu3P and stoichiometric amounts of Bu3SnF. The wide range of γ-(hetero)aryl-β-ketoesters that can be obtained illustrate the scope and limitations of this novel Hauser–Heck combination. γ-Aryl-β-ketoesters with a 1,3-dioxane acetal in the ortho position can easily be transformed into the hydroxy naphthoate in very good yield. Aqueous formic acid at 65 °C provides optimal conditions for this deprotective aromatization.
Co-reporter:Jan Roßbach, Klaus Harms, and Ulrich Koert
Organic Letters 2015 Volume 17(Issue 12) pp:3122-3125
Publication Date(Web):June 4, 2015
DOI:10.1021/acs.orglett.5b01427
The stereospecific BF3-mediated α-ketol rearrangement of β-hydroxy-α-ketoamides yields isolable 2-difluoroboranyloxy-3-keto-amides. X-ray and NMR analysis reveal a carbonyl coordination of the boron by the amide not the ketone. The boron complexes are air-stable solids, can be purified by silica gel chromatography, and exhibit novel reactivity in bromination and superior stereoselectivity in dipolar cycloaddition reactions.
Co-reporter:Niels Münster;Laura Werel;Georg Alexer Rennar;Klaus Harms
European Journal of Organic Chemistry 2015 Volume 2015( Issue 35) pp:7775-7784
Publication Date(Web):
DOI:10.1002/ejoc.201501136
Abstract
α-Bromosulfones have been synthesized diastereoselectively by reaction of β-hydroxy gem-dibromides with aromatic sulfinates. More steric demanding groups in the β-position led to increased stereoselectivity in these SN2 reactions. Lithiated α-bromosulfones react diastereoselectively with alkylating agents, aldehydes, and ketones. No configurational stability of the lithiated α-bromosulfones was observed except fast equilibration towards a chelate-stabilized intermediate. Treatment of the α-bromosulfone with methylcuprate resulted in substitution of the bromine by a methyl group.
Co-reporter:Jan Roßbach;Klaus Harms
European Journal of Organic Chemistry 2014 Volume 2014( Issue 5) pp:993-1006
Publication Date(Web):
DOI:10.1002/ejoc.201301548
Abstract
The Passerini reaction of vic-diketo amides with a variety of isocyanides and carboxylic acids has been examined. α-Acyloxy β-keto carboxamides were formed regioselectively as the major products. For the Passerini reactions with electron-withdrawing-group-substituted acetic acids, a one-pot Passerini–Knoevenagel reaction was accomplished by the addition of triethylamine.
Co-reporter:Julia Schütte;Frank Kilgenstein;Michel Fischer
European Journal of Organic Chemistry 2014 Volume 2014( Issue 24) pp:5302-5311
Publication Date(Web):
DOI:10.1002/ejoc.201402531
Abstract
A 2-unsubstituted indole adds under Cu-box-catalysis to mesoxalic ester amides with high enantioselectivity, whereas low enantiomeric excess is obtained for 2-substituted indoles. A mesoxalic ester amide is used as key component in the total syntheses of alkaloids cladoniamide G and cladoniamide F. The natural product syntheses involve Suzuki cross-coupling to a 2,2′-biindole, arylation of the vic-tricarbonyl compound, and intramolecular lactam formation.
Co-reporter:Dipl.-Chem. Mike Dischmann;Dr. Timo Frassetto;Dr. M. André Breuning ;Dr. Ulrich Koert
Chemistry - A European Journal 2014 Volume 20( Issue 36) pp:11300-11302
Publication Date(Web):
DOI:10.1002/chem.201403880
Abstract
The total synthesis of the heptacyclic natural product isoquinocyclinone has been achieved. A Hauser annulation was used to assemble the anthraquinone core structure. The unique 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole substructure was prepared by alkyne addition to a lactone intermediate and subsequent Ni0-mediated cyanide addition, the conversion of an O,O- into an N,O-acetal, and final intramolecular N-alkylation.
Co-reporter:Philipp Reiß and Ulrich Koert
Accounts of Chemical Research 2013 Volume 46(Issue 12) pp:2773
Publication Date(Web):May 7, 2013
DOI:10.1021/ar400007w
Ion channels provide a conductance pathway for the passive transport of ions across membranes. These functional molecules perform key tasks in biological systems such as neuronal signaling, muscular control, and sensing. Recently, function-oriented synthesis researchers began to focus on ion channels with the goal of modifying the function of existing ion channels (ion selectivity, gating) or creating new channels with novel functions. Both approaches, ion channel engineering and de novo design, have involved synthetic chemists, biochemists, structural biologists, and neurochemists.Researchers characterize the function of ion channels by measuring their conductance in samples of biological membranes (patch clamp) or artificial membranes (planar lipid bilayers). At the single molecule level, these measurements require special attention to the purity of the sample, a challenge that synthetic chemists should be aware of. Ideally, researchers study the function of channels while also acquiring structural data (X-ray, NMR) to understand and predict how synthetic modifications alter channel function.Long-term oriented researchers would like to apply synthetic ion channels to single molecule sensing and to implantat these synthetic systems in living organisms as tools or for the treatment of channelopathies. In this Account, we discuss our own work on synthetic ion channels and explain the shift of our research focus from a de novo design of oligo-THFs and oligo-THF-amino acids to ion channel engineering. We introduce details about two biological lead structures for ion channel engineering: the gramicidin β6,3 helix as an example of a channel with a narrow ion conductance pathway and the outer membrane porins (OmpF, OmpG) with their open β-barrel structure. The increase and the reversal of ion selectivity of these systems and the hydrophobic match/mismatch of the channel with the phospholipid bilayer are of particular interest. For engineering ion channels, we need to supplement the single-point attachment of a synthetic modulator with the synthesis of a more challenging two-point attachment.The successful function-oriented synthesis of ion channels will require interdisciplinary efforts that include new electrophysiology techniques, efficient synthesis (peptide/protein/organic), and good structural analysis.
Co-reporter:Ruben Bartholomäus;Janina Bachmann;Christian Mang;Lars Ole Haustedt;Klaus Harms
European Journal of Organic Chemistry 2013 Volume 2013( Issue 1) pp:180-190
Publication Date(Web):
DOI:10.1002/ejoc.201201279
Abstract
A synthesis of the AB-ring substructure of granaticin A was developed. The pyranolactone moiety was stereoselectively accessed by Sharpless asymmetric dihydroxylation and subsequent oxa-Pictet–Spengler cyclization. The use of BF3·OEt2 resulted in the formation of the cis pyranolactone, whereas the combination of BF3·OEt2 with trifluoroacetic acid led to the trans isomer. The resulting hydroquinones were cleaved selectively by ozonolysis to dicarboxylic acids. An aryl Grignard reagent could be regioselectively added to unsymmetrical anhydrides. As an alternative strategy for the construction of the B-ring, a benzyne–furan cycloaddition could be established.
Co-reporter:Jan Roßbach;Julia Baumeister;Klaus Harms
European Journal of Organic Chemistry 2013 Volume 2013( Issue 4) pp:662-665
Publication Date(Web):
DOI:10.1002/ejoc.201201517
Abstract
Crotylboration of vic-diketoamides and vic-diketo esters was achieved with high diastereoselectivity and complementary regioselectivity. Whereas (E)-crotylboration of α,β-diketoamides resulted in high yields (91–99 %) of β-crotylated products obtained as a single diastereomer (anti), Lewis acid promoted crotylboration of α,β-diketo esters yielded the α-crotylated species with the anti product as main diastereomer.
Co-reporter:Jonas Schwaben;Niels Münster;Tobias Breuer;Michael Klues;Klaus Harms;Gregor Witte
European Journal of Organic Chemistry 2013 Volume 2013( Issue 9) pp:1639-1643
Publication Date(Web):
DOI:10.1002/ejoc.201201714
Abstract
6,13-Disubstituted pentacenes were synthesized. Their electrochemical and optical properties, in addition to their packing motifs in the solid state, were determined. Treatment of pentacenequinone with TMSCF3 (Ruppert's reagent) and deprotection led to 6,13-bis(trifluoromethyl)pentacene-6,13-diol, which was aromatized to 6,13-bis(trifluoromethyl)pentacene by using PBr3. 6,13-Dialkoxypentacenes were accessible by alkylation of the corresponding hydroquinopentacenes by using dialkyl sulfates. 6,13-Bis(trifluoromethyl)pentacene and 6,13-dimethoxypentacene exhibit slipped face-to-face π stacking in the solid state, whereas 6,13-diethoxypentacene forms pairs of π-stacking molecules in the solid state.
Co-reporter:Ruben Bartholomäus;Fabian Dommershausen;Dr. Markus Thiele;Narayan S. Karanjule;Dr. Klaus Harms ;Dr. Ulrich Koert
Chemistry - A European Journal 2013 Volume 19( Issue 23) pp:7423-7436
Publication Date(Web):
DOI:10.1002/chem.201204545
Abstract
A total synthesis of the proposed structures of fulicineroside and its aglycone fulicinerine is reported. The tetrasubstituted dibenzofuran substructure was accessible either through a Pd-mediated ortho-metalation or by an Ir-catalyzed meta-borylation. The synthesis of the β,β,α-linked trisaccharide consisting of D-olivose, L-rhodinose, and L-rhamnose was challenged by the unprecedented β-linked rhodinose. A Pd-catalyzed β-selective glycosylation of a 4-epi-rhodinose and a subsequent Mitsunobu inversion provided selectively the β-linked L-rhodinose-L-rhamnose disaccharide. Comparison with the reported data for the natural product and the aglycone suggests a misassignment of the structure of the natural product.
Co-reporter:Tobias Burckhardt, Klaus Harms, and Ulrich Koert
Organic Letters 2012 Volume 14(Issue 17) pp:4674-4677
Publication Date(Web):August 21, 2012
DOI:10.1021/ol302121w
A convergent total synthesis of the structurally unprecedented alkaloid lodopyridone was achieved using a cross-coupling of an iodopyridone fragment with a quinolinethiazolylstannane. Key features of the syntheses of the pentasubstituted 4-pyridone were a regioselective bromination of a 4-pyridone derived from kojic acid, a subsequent Cu-mediated introduction of the thioether, and a directed lithiation/iodination step. A chemoselective Negishi cross-coupling of a dibromothiazole and a quinolinylzinc reagent was used to assemble the chloroquinolinethiazol moiety.
Co-reporter:Niels Münster, Klaus Harms and Ulrich Koert
Chemical Communications 2012 vol. 48(Issue 13) pp:1866-1867
Publication Date(Web):20 Dec 2011
DOI:10.1039/C2CC17599A
A novel directed SN2 reaction of conformationally biased gem-dibromides and an arenesulfinate anion is described. The reaction results in the diastereoselective formation of α-bromosulfones. The selectivity originates from pre-coordination of the nucleophile to a free hydroxyl group in the γ-position.
Co-reporter:Malte Wohlfahrt;Klaus Harms
European Journal of Organic Chemistry 2012 Volume 2012( Issue 11) pp:2260-2265
Publication Date(Web):
DOI:10.1002/ejoc.201200059
Abstract
The total synthesis of (+)-awajanomycin has been achieved by asymmetric allylboration of a vicinal tricarbonyl compound as the key step. A substrate-controlled dihydroxylation and subsequent differentiation of diastereotopic ester groups were used to synthesize the γ-lactone substructure. After formation of the δ-lactam, the bicyclic core structure was established. The synthetic strategy and overall efficacy is compared with Huang's route to awajanomycin.
Co-reporter:Janina Bachmann;Christian Mang;Lars Ole Haustedt;Klaus Harms
European Journal of Organic Chemistry 2012 Volume 2012( Issue 33) pp:6562-6569
Publication Date(Web):
DOI:10.1002/ejoc.201201104
Abstract
The BCD-ring substructure of granaticin A was synthesised following a new approach for the construction of the naphthoquinone moiety. The 2-oxabicyclo[2.2.2]oct-5-ene substructure was accessible stereoselectively using a Sharpless asymmetric dihydroxylation and a diastereoselective ketone reduction in combination with Yoshii's route. The naphthoquinone B-ring was prepared by addition of an aryllithium intermediate to an anhydride followed by a Friedel–Crafts cyclisation mediated by AlCl3 and Mg(OTf)2. The success of the Friedel–Crafts cyclisation relied on the conversion of the ketone-carboxylic acid into a lactone acetal.
Co-reporter:M. André Breuning, Klaus Harms, and Ulrich Koert
Organic Letters 2011 Volume 13(Issue 6) pp:1402-1405
Publication Date(Web):February 21, 2011
DOI:10.1021/ol200085g
A convergent and effective synthesis of the pyrrolopyrrole substructure (CDEFG) of the isoquinocyclines is reported. A key step is a tin−lithium exchange of an imidato-alkenyltin compound (a ring G equivalent) and the subsequent acylation with a lactone. The resulting acetal is used successfully for the ring F closure to the pyrrolopyrrole. The sole formation of the isoquinocycline N,O-acetal epimer is in accordance with the proposed mechanism for the isomerization of quinocyclines to isoquinocyclines.
Co-reporter:Katharina Gries;Kathrin Bubel;Malte Wohlfahrt;Seema Agarwal;Andreas Greiner
Macromolecular Chemistry and Physics 2011 Volume 212( Issue 23) pp:
Publication Date(Web):
DOI:10.1002/macp.201100449
Abstract
Poly(L-menthyl methacrylate) (PMenMA) is synthesized by atom transfer radical polymerization (ATRP) of methyl L-mentholacrylate using bis[2-(2-bromoisobutyrooxy)ethyl]disulfide] ((BiBOE)2)S2) as the ATRP coinitiator. Reduction of hydrogen tetrachloroaureate(III) (HAuCl4 ·3 H2O) by Super-Hydride in the presence of PMenMA yields gold nanoparticles (AuNP)–PMenMA conjugates in the size range of 2–20 nm, depending on the ratio of PMenMA and HAuCl4. AuNP–PMenMA is characterized by TEM, NMR, IR-, and UV-spectroscopy. The correlation of the ratio of (AuNP)–PMenMA conjugates and free PMenMA is analyzed by gel permeation chromatography (GPC).
Co-reporter:Katharina Gries;Kathrin Bubel;Malte Wohlfahrt;Seema Agarwal;Andreas Greiner
Macromolecular Chemistry and Physics 2011 Volume 212( Issue 23) pp:
Publication Date(Web):
DOI:10.1002/macp.201190050
Co-reporter:Dr. Johannes SchulzeWischeler;Dong Sun;Nicola U. Sner;Dr. Uwe Linne;Dr. Andreas Heine;Dr. Ulrich Koert;Dr. Gerhard Klebe
Chemistry - A European Journal 2011 Volume 17( Issue 21) pp:5842-5851
Publication Date(Web):
DOI:10.1002/chem.201002437
Abstract
The carbonic anhydrase II mutant His64Cys was prepared and applied to tethered alkyne/azide cycloaddition reactions. The azide component could be tethered to the enzyme surface through a disulfide bridge, while the alkyne component was reversibly coordinated through a sulfonamide anchor to the zinc ion in the original catalytic center of the enzyme. The incipient orientation of the reactants in the binding site and of the formed triazole product were characterized by crystallography. The reaction progression could be monitored by HPLC-MS analysis.
Co-reporter:Dipl.-Chem. Malte Wohlfahrt;Dr. Klaus Harms ;Dr. Ulrich Koert
Angewandte Chemie 2011 Volume 123( Issue 36) pp:8554-8556
Publication Date(Web):
DOI:10.1002/ange.201103679
Co-reporter:Dipl.-Chem. Malte Wohlfahrt;Dr. Klaus Harms ;Dr. Ulrich Koert
Angewandte Chemie International Edition 2011 Volume 50( Issue 36) pp:8404-8406
Publication Date(Web):
DOI:10.1002/anie.201103679
Co-reporter:Wolfgang Grosse; Dr. Lars-Oliver Essen ; Dr. Ulrich Koert
ChemBioChem 2011 Volume 12( Issue 6) pp:830-839
Publication Date(Web):
DOI:10.1002/cbic.201000793
Abstract
Membranes form natural barriers that need to be permeable to diverse matter like ions and substrates. This permeability is controlled by ion-channel proteins, which have attracted great interest for pharmaceutical applications. Ion-channel engineering (ICE) modifies biological ion channels by chemical/biological synthetis means. The goal is to obtain ion channels with modified or novel functionality. Three functional strategies exist. The first is the manipulation of the wider pores with robust β-barrel structures, such as those of α-hemolysin and porins. The second engineering approach focuses on the modification of narrow (mostly α-helical) pores to understand selectivity and modes of action. A third functional approach addresses channel gating by (photo)triggering the biological receptor that controls the channel. Several synthetis strategies have been developed and successfully utilized for the synthetic modification of biological ion-channels: the S-alkylation of specifically introduced Cys, protein semisynthesis by native chemical ligation, protein semisynthesis by protein trans-splicing, as well as nonsense-suppression methods. Structural studies (X-ray crystallography, NMR spectroscopy) are necessary to support the functional studies and to afford predictable engineering. The reprogramming and re-engineering of channels can be used for sensing applications, treatment of channelopathies, chemical neurobiology, and providing novel lead compounds for targeting ion channels.
Co-reporter:Jens Cordes, Klaus Harms and Ulrich Koert
Organic Letters 2010 Volume 12(Issue 17) pp:3808-3811
Publication Date(Web):August 10, 2010
DOI:10.1021/ol101500k
The synthesis of the pyrrolopyrrole substructure of the isoquinocyclines is reported. The pentacyclic (CDEFG) substructure of isoquinocycline A and B, which contains an unusual 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole (FG) connected via an N,O-spiro acetal to the anthraquinoid core of the isoquinocycline aglycon has been synthesized. Key steps were a nickel(0)-mediated hydrocyanation of an alkynone, the conversion of an O,O-acetal into an N,O-acetal, and an intramolecular amidine alkylation.
Co-reporter:Wolfgang Grosse, Philipp Reiß, Simon Reitz, Menekse Çebi, Wolger Lübben, Ulrich Koert, Lars-Oliver Essen
Bioorganic & Medicinal Chemistry 2010 Volume 18(Issue 22) pp:7716-7723
Publication Date(Web):15 November 2010
DOI:10.1016/j.bmc.2010.03.044
Chemical modification of ion channels has recently attracted attention due to their potential use in stochastic sensing and neurobiology. Among the available channel templates stable β-barrel proteins have shown their potential for large scale chemical modifications due to their wide pore lumen. Ion-channel hybrids using the outer membrane protein OmpG were generated by S-alkylation with a synthetic modulator and functionally as well as structurally characterized. The dansyl moiety of the used modulator resulted in partial blockage of current though the OmpG channel with its gating characteristics mainly unaffected. The crystal structure of an OmpG–dansyl hybrid at 2.4 Å resolution correlates this finding by showing that the modulator lines the inner walling of the OmpG pore. These results underline the suitability of OmpG as a structural base for the construction of stochastic sensors.The first structure of the OmpG porin covalently modified by a synthetic compound is reported. Intimate lining of the modulator to the pore interior leads to partial current blockage.
Co-reporter:Björn Gebhardt Dr.;ChristianM. König Dr.;Cornelia Schleth Dr.;Mario Dauber Dr.
Chemistry - A European Journal 2010 Volume 16( Issue 20) pp:5934-5941
Publication Date(Web):
DOI:10.1002/chem.201000104
Abstract
The importance for the right order of functional group introduction and manipulation (good timing) was demonstrated in the course of a total synthesis of phoslactomycin A. The synthetic strategy comprised a CuI–thiophene carboxylate (CuTC, Liebeskind’s reagent)-mediated coupling to introduce the Z,Z-diene at the final stage of the synthesis in the presence of a protected phosphate. Key features for the assembly of the C1–C13 fragment were an asymmetric dihydroxylation, an Evans-aldol reaction and an advanced protective group strategy. The C14–C21 fragment was accessible via an asymmetric 1,2-addition to cyclohexenone and a subsequent diastereoselective ketone reduction. One crucial task was the dihydroxylation of the C8–C9 alkene, the introduction of the C6–C7 double bond and the generation of the C25-nitrogen functionality. A second example consisted of the best sequence for the generation of the functional groups in the core part (first phosphorylation, second iodo-olefination, third azide/carbamate conversion). The synthetic solutions from this approach are compared with the already existing contributions in the phoslactomycin area.
Co-reporter:Christian M. König, Björn Gebhardt, Cornelia Schleth, Mario Dauber and Ulrich Koert
Organic Letters 2009 Volume 11(Issue 13) pp:2728-2731
Publication Date(Web):June 1, 2009
DOI:10.1021/ol900757k
A convergent total synthesis of the PP2A-inhibitor phoslactomycin A was achieved using a CuTC-mediated coupling of an alkenyl iodide C1−C13 fragment with an C14−C21 alkenyl stannane in the presence of a protected phosphate. Key features for the assembly of the C1−C13 fragment were an asymmetric dihydroxylation, an Evans−Aldol reaction, and a well-balanced protective group strategy. An asymmetric 1,4-addition to cyclohexenone was the key step in the preparation of the C14−C21 fragment.
Co-reporter:Simon Reitz;Menekse Cebi;Philipp Reiß;Gregor Studnik;Uwe Linne, Dr. ;Lars-Oliver Essen Dr.
Angewandte Chemie International Edition 2009 Volume 48( Issue 26) pp:
Publication Date(Web):
DOI:10.1002/anie.200990133
Co-reporter:Simon Reitz;Menekse Cebi;Philipp Reiß;Gregor Studnik;Uwe Linne, Dr. ;Lars-Oliver Essen Dr.
Angewandte Chemie 2009 Volume 121( Issue 26) pp:4947-4951
Publication Date(Web):
DOI:10.1002/ange.200900457
Co-reporter:Simon Reitz;Menekse Cebi;Philipp Reiß;Gregor Studnik;Uwe Linne, Dr. ;Lars-Oliver Essen Dr.
Angewandte Chemie 2009 Volume 121( Issue 26) pp:
Publication Date(Web):
DOI:10.1002/ange.200990135
Co-reporter:Steffen Brenzel;Menekse Cebi Dr.;Philipp Reiß Dr. Dr.;Henning D. Mootz Dr.
ChemBioChem 2009 Volume 10( Issue 6) pp:983-986
Publication Date(Web):
DOI:10.1002/cbic.200900039
Co-reporter:Simon Reitz;Menekse Cebi;Philipp Reiß;Gregor Studnik;Uwe Linne, Dr. ;Lars-Oliver Essen Dr.
Angewandte Chemie International Edition 2009 Volume 48( Issue 26) pp:4853-4857
Publication Date(Web):
DOI:10.1002/anie.200900457
Co-reporter:Philipp Reiß Dr.;Loay Al-Momani Dr. Dr.
ChemBioChem 2008 Volume 9( Issue 3) pp:377-379
Publication Date(Web):
DOI:10.1002/cbic.200700519
Co-reporter:Ute Fröhlich;M.-Elisa Juarez Garcia
European Journal of Organic Chemistry 2007 Volume 2007(Issue 12) pp:1991-1999
Publication Date(Web):2 MAR 2007
DOI:10.1002/ejoc.200700068
A ring-closing olefin metathesis (RCM) to an eight-membered ring is suitable to induce a conformational switch of a 2,3,6,7-tetrasubstituted cis-decalin. The double-ring flip of the decalin scaffold can be reversed by a ring-opening metathesis. The corresponding RCM to a 14-membered ring does not force the double ring flip to occur. A ring-size competition experiment resulted in the exclusive formation of an eight-membered ring. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Co-reporter:Michael Rommel;Alexer Ernst and
European Journal of Organic Chemistry 2007 Volume 2007(Issue 26) pp:4408-4430
Publication Date(Web):3 JUL 2007
DOI:10.1002/ejoc.200700333
Efficient syntheses of three novel scaffolds for potential β-glycosidase inhibitors were developed: The first consists of a 2,7-dioxabicyclo[2.2.1]heptane derivative, which was prepared by an intramolecular ketalisation. The second scaffold consists of a hydroxylated cyclopentylamine, which could be synthesised stereoselectively from 2-azabicyclo[2.2.1]hept-5-en-3-one. The third scaffold, a 4,5-dihydroxynicotinic acid, was accessible through a sequence of substituent directed ortho-lithiations. Selected compounds were tested as inhibitors for a number of glycosidases. Three nicotinic acid derivatives were found to be selective β-glucosidase inhibitors.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Co-reporter:Menekse Cebi Dr.
ChemBioChem 2007 Volume 8(Issue 9) pp:
Publication Date(Web):10 MAY 2007
DOI:10.1002/cbic.200700113
Taste the seasoning. Sensing of the pungent principles of mustard and horseradish is caused by a covalent protein modification that activates the ion-channel receptor involved rather than a direct lock-and-key mechanism.
Co-reporter:Sabine Schröder;Anna K. Schrey;Andrea Knoll;Philipp Reiß;Burkhard Ziemer
European Journal of Organic Chemistry 2006 Volume 2006(Issue 12) pp:
Publication Date(Web):10 APR 2006
DOI:10.1002/ejoc.200600068
The stereoselective synthesis of a cis-2,6-disubstituted tetrahydropyran bearing a δ-amino acid has been achieved starting from N-Boc-leucinal. The THP amino acid was incorporated into peptide sequences and the structural consequences were studied by X-ray crystallography and NMR analysis. Single-channel current measurements showed that the THP amino acid is a suitable substitute for positions 11 and 12 of the gramicidin ion channel. The resulting hybrid ion channel revealed Eisenman I ion selectivity and an ion-dependence of the channel dwell time. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Co-reporter:J. René Backes
European Journal of Organic Chemistry 2006 Volume 2006(Issue 12) pp:
Publication Date(Web):10 APR 2006
DOI:10.1002/ejoc.200600106
The monomeric unit of the macrodiolide SCH 351448 has been synthesized from three building blocks. Strategic disconnections were chosen between C21–C22 (Wittig) and C10–C11 (stereoselective aldol). The cis configuration of both 2,6-disubstituted tetrahydropyran rings was established by a stereoselective cationic reduction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Co-reporter:Peter T. Daniel Dr. Dr.;Julia Schuppan Dr.
Angewandte Chemie 2006 Volume 118(Issue 6) pp:
Publication Date(Web):11 JAN 2006
DOI:10.1002/ange.200502698
Der Naturstoff Apoptolidin führt selektiv bei bestimmten Krebszelllinien zum programmierten Zelltod. Dieser auch als Apoptose bezeichnete Vorgang ist ein wichtiger zellbiologischer Mechanismus zur Regulation von Homöostase und Morphogenese. Apoptotische Fehlregulationen sind mit verschiedenen Krankheiten verknüpft, insbesondere Krebs. Der extrinsische Weg zur Apoptose führt über Todesliganden und Todesrezeptoren zur Aktivierung einer Caspase-Kaskade, die den proteolytischen Abbau der Zellarchitektur bewirkt. Die intrinsisch ausgelöste Apoptose beginnt mit der Übermittlung von Schäden im Zellinnern an das Mitochondrium, das seine strukturelle Integrität verliert und ein Apoptosom bildet, das die Caspase-Kaskade auslöst. Apoptoseregulierende Verbindungen sind von großer medizinischer Bedeutung. Viele Naturstoffe regulieren apoptotische Abläufe, so auch Apoptolidin. Die bekannten synthetischen Zugänge zu Apoptolidin werden in diesem Aufsatz beschrieben und verglichen. Weitere apoptoseregulierende Naturstoffe werden ebenfalls kurz vorgestellt.
Co-reporter:Hermut Wehlan Dr.;Mario Dauber;M. Teresa Mujica Fernaud Dr.;Julia Schuppan Dr.;Sonja Keiper Dr.;Rainer Mahrwald Priv.-Doz. Dr.;M.-Elisa Juarez Garcia Dipl.-Chem. Dr.
Chemistry - A European Journal 2006 Volume 12(Issue 28) pp:
Publication Date(Web):25 JUL 2006
DOI:10.1002/chem.200600462
The total synthesis of apoptolidin A is described employing an early glycosylation strategy. Strategic disconnections were chosen between C11–C12 (cross-coupling) and C19O–C1 (macrocyclization). The cis-selective glycosylation at C9-OH was achieved with the new SIBA protective group at O2/O3 of the L-glucose residue. Auxiliary substitutents at the 2-position of the 2-deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide. The cross-coupling of the glycosylated northern half with the glycosylated southern half was achieved with CuI-thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20-membered macrolide selectively. H2SiF6 was suitable for the final deprotection of the silyl ethers and the conversion of the C21 methylketal into the hemiketal. The synthetic flexibility of the approach was proven by the synthesis of some glycovariants.
Co-reporter:Julia Schuppan Dr.;Hermut Wehlan Dr.;Sonja Keiper Dr. Dr.
Chemistry - A European Journal 2006 Volume 12(Issue 28) pp:
Publication Date(Web):25 JUL 2006
DOI:10.1002/chem.200600461
An efficient stereocontrolled synthesis of apoptolidinone A, the aglycone of apoptolidin A is described. The synthetic strategy relies on a cross coupling between C11/C12 of a northern half (C1–C11) and a southern part (C12–C28) followed by a ring-size selective macrolactonization. Key steps for the introduction of the southern half stereocenters are a stereoselective aldol reaction, a substrate controlled dihydroxylation and a chelation-controlled Grignard/aldehyde addition. The conjugated triene of the northern half was built up successively by E-selective Wittig reactions. L-Malic acid was chosen as the chiral pool source for the C8/C9 stereocenters. The final cleavage of the silyl ethers and the conversion of the C21 methyl ketal into the hemiketal was achieved by HF⋅pyridine.
Co-reporter:Jochen R. Pfeifer, Philipp Reiß,Ulrich Koert
Angewandte Chemie International Edition 2006 45(3) pp:501-504
Publication Date(Web):
DOI:10.1002/anie.200502570
Co-reporter:Peter T. Daniel, Ulrich Koert,Julia Schuppan
Angewandte Chemie International Edition 2006 45(6) pp:872-893
Publication Date(Web):
DOI:10.1002/anie.200502698
Co-reporter:Jochen R. Pfeifer Dipl.-Chem.;Philipp Reiß Dr. Dr.
Angewandte Chemie 2006 Volume 118(Issue 3) pp:
Publication Date(Web):8 DEC 2005
DOI:10.1002/ange.200502570
Kanal mit Ionenwahl: Eine vorhersagbare Ionenselektivität ist für den Einsatz synthetischer Ionenkanäle in biologischen Systemen unabdingbar. Gramicidin A ist eine geeignete Leitstruktur für das Design solcher Kanäle. Das im Bild gezeigte Kronenether-Gramicidin-Hybrid bildet Ionenkanäle, die eine höhere Ionenselektivität für K+ als für Cs+ aufweisen.
Co-reporter: Dr. Ulrich Koert
Physical Chemistry Chemical Physics 2005 vol. 7(Issue 7) pp:1501-1506
Publication Date(Web):07 Mar 2005
DOI:10.1039/B418561G
Various synthetic ion channels were derived from the gramicidin A β-helix-lead structure. The ion transport through these channels was studied by single-channel current measurements in planar lipid bilayers. For asymmetric THF-gramicidin hybrids a selective insertion into the phospholipid bilayer was observed. Ion-selectivity could be achieved by the use of synthetic cyclohexyl-ether amino acids as channel building blocks. The balance between the desolvation energy and the binding energy inside the channel is discussed. For minigramicidins, the hydrophobic coupling of the channel with membranes of different thickness was studied by dwelltime analysis. A conformational switch of a double stranded β-helix into a single stranded β-helix was observed upon addition of Cs+-ions.
Co-reporter:Hermut Wehlan Dipl.-Chem.;Mario Dauber;M.-Teresa Mujica Fernaud Dr.;Julia Schuppan Dr.;Rainer Mahrwald Priv.-Doz. Dr.;Burkhard Ziemer Dr.;M.-Elisa Juarez Garcia Dipl.-Chem. Dr.
Angewandte Chemie 2004 Volume 116(Issue 35) pp:
Publication Date(Web):1 SEP 2004
DOI:10.1002/ange.200460172
Eine ringgrößenselektive Makrolactonisierung und die frühe Einführung der Zuckerbausteine sind die Hauptmerkmale einer Totalsynthese des 20-gliedrigen Makrolids Apoptolidin (siehe Bild), das bei transformierten Ratten-Gliazellen spezifisch den Zelltod auslösen kann.
Co-reporter:Daniel Garbe;Stephan A. Sieber Dr.;Nina G. Bur ;Mohamed A. Marahiel
ChemBioChem 2004 Volume 5(Issue 7) pp:
Publication Date(Web):1 JUL 2004
DOI:10.1002/cbic.200400042
A key to the development of new antibiotics with increased efficiency can be found in (E)-alkene dipeptide isosteres. Here we report on the incorporation of such a dipeptide isostere into a linear peptide precursor by chemical synthesis in combination with enzymatic cyclisation.
Co-reporter:Hans-Dieter Arndt Dr.;Rüdiger Welz Dr.;Sabine Müller Dr.;Burkhart Ziemer Dr. Dr.
Chemistry - A European Journal 2004 Volume 10(Issue 16) pp:
Publication Date(Web):28 JUN 2004
DOI:10.1002/chem.200400181
The 2,5-trans-substituted oligopyrrolidines constitute a promising class of novel RNA-binding agents as well as potential building blocks for artificial anion channels. A convergent synthesis of terpyrrolidine 1 and pyrrolidino-THF-pyrrolidine 2 is reported, relying upon convergent coupling of 2,5-trans-pyrrolidinecarboxaldehydes through bridging alkyne units under Felkin–Anh control and subsequent closure of the central ring. After complete deprotection, the free polyamine products were isolated in excellent yield and purity. Crystal structure analyses of a terpyrrolidine and a pyrrolidino-THF-pyrrolidine documented their helical privileged conformations. The compounds were then screened for RNA cleavage activity. Unlike the only weakly active simple polyamines, p-nitrosulfonamide 33 was found to induce cleavage at mM concentrations under physiologically relevant conditions.
Co-reporter:Ulrich Koert Dr.
Angewandte Chemie 2004 Volume 116(Issue 42) pp:
Publication Date(Web):20 OCT 2004
DOI:10.1002/ange.200461097
Eine nicht ungefährliche Ernährung: Die hochtoxische Substanz Tetrodotoxin (siehe Bild) ist im Körper des Kugelfisches enthalten, der als kulinarische Spezialität gilt. Die Synthese dieses Giftes ist eine schwierige präparative Aufgabe, die nun allerdings von drei Gruppen mithilfe unterschiedlicher Strategien gelöst worden ist.
Co-reporter:Ulrich Koert Dr.
Angewandte Chemie International Edition 2004 Volume 43(Issue 42) pp:
Publication Date(Web):20 OCT 2004
DOI:10.1002/anie.200461097
A meal of carefully prepared puffer fish, which hopefully does not contain the toxic livers and ovaries, tests the courage of gourmets and cooks. Tetrodotoxin (formula shown), the poisonous principle of the puffer fish, presents a challenge for synthesis, which has been mastered by three teams using different strategies and key steps.
Co-reporter:Hermut Wehlan Dipl.-Chem.;Mario Dauber;M.-Teresa Mujica Fernaud Dr.;Julia Schuppan Dr.;Rainer Mahrwald Priv.-Doz. Dr.;Burkhard Ziemer Dr.;M.-Elisa Juarez Garcia Dipl.-Chem. Dr.
Angewandte Chemie International Edition 2004 Volume 43(Issue 35) pp:
Publication Date(Web):1 SEP 2004
DOI:10.1002/anie.200460172
A ring-size-selective macrolactonization and the early introduction of the saccharide portions are the main features of a total synthesis of the 20-membered macrolide apoptolidin (see formula), which induces apoptosis in rat glia cells transformed with oncogenes.
Co-reporter:Andrea Vescovi, Andrea Knoll and Ulrich Koert
Organic & Biomolecular Chemistry 2003 vol. 1(Issue 16) pp:2983-2997
Publication Date(Web):11 Jul 2003
DOI:10.1039/B303249N
THF–gramicidin hybrids 2–4 with the L-THF amino acid 1 in positions 11 and 12 and compounds 5–8 with the D-THF amino acid ent-1 in positions 10 and 11 were synthesized and their ion channel properties were studied by single-channel-current analysis. The replacement of positions 11 and 12 by the L-THF amino acid 1 gave a strongly reduced channel performance. In contrast, replacement of positions 10 and 11 by the D-THF amino acid ent-1 gave rise to new and interesting channel properties. For the permeability ratios, the ion selectivity shifts from Eisenman I towards Eisenman III selectivity and the channels display ms-dynamics. Most remarkable is the asymmetric compound 8, which inserts selectively into a DPhPC membrane and displays voltage-directed gating dynamics.
Co-reporter:Michael Karle Dipl.-Chem.;Dirk Bockelmann Dipl.-Chem.;Dirk Schumann Dipl.-Chem.;Christian Griesinger Dr. Dr.
Angewandte Chemie 2003 Volume 115(Issue 37) pp:
Publication Date(Web):25 SEP 2003
DOI:10.1002/ange.200352130
Über ein 14-gliedriges Bislactam gelang die Kupplung zweier konformativ schaltbarer Decalineinheiten (siehe Molekülstruktur, TBDPS=tert-Butyldiphenylsilyl). Das Lösen einer Bisacetalklammer am linken Molekülende führt zu einem Doppelringflip in der linken Decalineinheit, der durch konformative Kupplung über das 14-gliedrige Bislactam einen Doppelringflip in der rechten Decalineinheit induziert.
Co-reporter:Michael Karle Dipl.-Chem.;Dirk Bockelmann Dipl.-Chem.;Dirk Schumann Dipl.-Chem.;Christian Griesinger Dr. Dr.
Angewandte Chemie International Edition 2003 Volume 42(Issue 37) pp:
Publication Date(Web):25 SEP 2003
DOI:10.1002/anie.200352130
Passing on information. Two conformational switches, decalin units, were coupled to a 14-membered bislactam ring (see formula, TBDPS=tert-butyldiphenylsilyl). Removal of a bisacetal clamp on the left side of the molecule resulted in a double ring-flip of the left decalin unit. Conformational coupling through the bislactam unit led to a double ring-flip in the right decalin unit.
Co-reporter:Ulrich Koert, Philipp Reiß
Journal of Supramolecular Chemistry 2002 Volume 2(1–3) pp:29-37
Publication Date(Web):January–June 2002
DOI:10.1016/S1472-7862(02)00070-9
Co-reporter:Hans-Dieter Arndt Dr.;Dirk Bockelmann Dipl.-Chem.;Andrea Knoll Dr.;Stefanie Lamberth Dr.;Christian Griesinger Dr. Dr.
Angewandte Chemie International Edition 2002 Volume 41(Issue 21) pp:
Publication Date(Web):31 OCT 2002
DOI:10.1002/1521-3773(20021104)41:21<4062::AID-ANIE4062>3.0.CO;2-U
Variable ion channels: A 22mer peptide derived from the D,L-peptide gramicidin A changes from an inactive to a highly ion-channel-active conformation (see picture). The helical structure of the active and inactive conformations was characterized by NMR spectroscopy and circular dichroism; conductance measurements led to the conclusion that there are two symmetrical binding sites for the Cs atom in the active form.
Co-reporter:Hans-Dieter Arndt Dr.;Dirk Bockelmann Dipl.-Chem.;Andrea Knoll Dr.;Stefanie Lamberth Dr.;Christian Griesinger Dr. Dr.
Angewandte Chemie 2002 Volume 114(Issue 21) pp:
Publication Date(Web):31 OCT 2002
DOI:10.1002/1521-3757(20021104)114:21<4234::AID-ANGE4234>3.0.CO;2-S
Verwandelbarer Ionenkanal: Ein 22mer-Peptid, das vom D,L-Peptid Gramicidin A abgeleitet wurde, wandelt sich bei Zugabe von Cs+ aus einer inaktiven in eine höchst ionenkanalaktive Konformation um (siehe Bild). Die helicalen Strukturen der aktiven und inaktiven Form wurden durch NMR-Spektroskopie und Circulardichroismus charakterisiert; Leitfähigkeitsmessungen ließen auf zwei symmetrische Bindungsstellen für die Cs-Atome in der aktiven Form schließen.
Co-reporter:Niels Münster, Klaus Harms and Ulrich Koert
Chemical Communications 2012 - vol. 48(Issue 13) pp:NaN1867-1867
Publication Date(Web):2011/12/20
DOI:10.1039/C2CC17599A
A novel directed SN2 reaction of conformationally biased gem-dibromides and an arenesulfinate anion is described. The reaction results in the diastereoselective formation of α-bromosulfones. The selectivity originates from pre-coordination of the nucleophile to a free hydroxyl group in the γ-position.
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![Stannane,tributyl[(1E)-3-[(4-methoxyphenyl)methoxy]-1-methyl-1-propenyl]-](http://img.cochemist.com/ccimg/145300/145222-50-0_b.png)
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![Quinoline, 2-[[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]oxy]methyl]-](http://img.cochemist.com/ccimg/142900/142820-33-5_b.png)
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![Cyclohexanone, 3-[2-(tributylstannyl)ethenyl]-, (Z)-](/data/chemimg/1116300/141262-53-5_b.png)
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![[(S)-BINAPRuCl(benzene)]Cl](http://img.cochemist.com/ccimg/126300/126251-92-1.png)
![[(S)-BINAPRuCl(benzene)]Cl](http://img.cochemist.com/ccimg/126300/126251-92-1_b.png)
![Hexahydro-furo[3,2-b]furan-3,6-diamine](http://img.cochemist.com/ccimg/125400/125335-70-8.png)
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![2(5H)-Furanone,3-[(2R,13R)-2,13-dihydroxy-13-[(2S,2'S,5R,5'R)-octahydro-5'-[(1S)-1-hydroxyundecyl][2,2'-bifuran]-5-yl]tridecyl]-5-methyl-,(5S)-](http://img.cochemist.com/ccimg/111100/111056-97-4_b.png)
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![(2S,3R,4S,5R)-2-[[(4R,6S,6AR,9S)-2-HYDROXY-3,6,9-TRIMETHYL-4-(2-METHYLPROP-1-ENYL)-5,6,6A,7,8,9-HEXAHYDRO-4H-PHENALEN-1-YL]OXY]OXANE-3,4,5-TRIOL](http://img.cochemist.com/data/images/104855-20-1_b.png)
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![1H-Isoindole-1,3(2H)-dione, 2-[2-(2-bromoethoxy)ethyl]-](http://img.cochemist.com/ccimg/87000/86927-03-9.png)
![1H-Isoindole-1,3(2H)-dione, 2-[2-(2-bromoethoxy)ethyl]-](http://img.cochemist.com/ccimg/87000/86927-03-9_b.png)
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![2-{[(dodecyloxy)(hydroxy)phosphoryl]oxy}-N,N,N-trimethylethanaminium chloride](http://img.cochemist.com/ccimg/54000/53949-18-1_b.png)
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![Spiro[1,4-methanoanthra[2,3-d]oxepin-2(1H),2'(1'H)-pyrrolo[2,3-b]pyrrole]-7,12-dione,5-[[2,6-dideoxy-4-C-(1-hydroxyethyl)-a-L-xylo-hexopyranosyl]oxy]-4,4',5,5'-tetrahydro-8,13-dihydroxy-4-methyl-,(1S,2R,4R,5R)-](http://img.cochemist.com/ccimg/37400/37332-17-5_b.png)
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![3,5,9-Trioxa-4-phosphaheptacos-18-en-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[[(9Z)-1-oxo-9-octadecen-1-yl]oxy]-, innersalt, 4-oxide, (7R,18Z)-](http://img.cochemist.com/ccimg/4300/4235-95-4_b.png)
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![(3r,3ar,6s,6as)-6-[tert-butyl(dimethyl)silyl]oxy-2,3,3a,5,6,6a-he Xahydrofuro[3,2-b]furan-3-ol](http://img.cochemist.com/ccimg/205000/204909-70-6.png)
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![Propanoic acid,2-methyl-,(1S,3R)-3-[(1Z,3Z,5R,7R,8R,9E)-8-(2-aminoethyl)-10-[(2S,3S)-3-ethyl-3,6-dihydro-6-oxo-2H-pyran-2-yl]-5,8-dihydroxy-7-(phosphonooxy)-1,3,9-decatrien-1-yl]cyclohexylester](http://img.cochemist.com/ccimg/122900/122856-25-1.png)
![Propanoic acid,2-methyl-,(1S,3R)-3-[(1Z,3Z,5R,7R,8R,9E)-8-(2-aminoethyl)-10-[(2S,3S)-3-ethyl-3,6-dihydro-6-oxo-2H-pyran-2-yl]-5,8-dihydroxy-7-(phosphonooxy)-1,3,9-decatrien-1-yl]cyclohexylester](http://img.cochemist.com/ccimg/122900/122856-25-1_b.png)
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