Co-reporter:Damien Baud;Jack W. E. Jeffries;Thomas S. Moody;John M. Ward
Green Chemistry (1999-Present) 2017 vol. 19(Issue 4) pp:1134-1143
Publication Date(Web):2017/02/21
DOI:10.1039/C6GC02769E
Transaminase enzymes have significant potential for the sustainable synthesis of amines using mild aqueous reaction conditions. Here a metagenomics mining strategy has been used for new transaminase enzyme discovery. Starting from oral cavity microbiome samples, DNA sequencing and bioinformatics analyses were performed. Subsequent in silico mining of a library of contiguous reads built from the sequencing data identified 11 putative Class III transaminases which were cloned and overexpressed. Several screening protocols were used and three enzymes selected of interest due to activities towards substrates covering a wide structural diversity. Transamination of functionalized cinnamaldehydes was then investigated for the production of valuable amine building blocks.
Co-reporter:Alice Dunbabin;Fabiana Subrizi;John M. Ward;Tom D. Sheppard
Green Chemistry (1999-Present) 2017 vol. 19(Issue 2) pp:397-404
Publication Date(Web):2017/01/23
DOI:10.1039/C6GC02241C
Furfural is recognised as an attractive platform molecule for the production of solvents, plastics, resins and fuel additives. Furfurylamines have many applications as monomers in biopolymer synthesis and for the preparation of pharmacologically active compounds, although preparation via traditional synthetic routes is not straightforward due to by-product formation and sensitivity of the furan ring to reductive conditions. In this work transaminases (TAms) have been investigated as a mild sustainable method for the amination of furfural and derivatives to access furfurylamines. Preliminary screening with a recently reported colorimetric assay highlighted that a range of furfurals were readily accepted by several transaminases and the use of different amine donors was then investigated. Multistep synthetic routes were required to synthesise furfurylamine derivatives for use as analytical standards, highlighting the benefits of using a one step biocatalytic route. To demonstrate the potential of using TAms for the production of furfurals, the amination of selected compounds was then investigated on a preparative scale.
Co-reporter:Sally Higson, Fabiana Subrizi, Tom D. Sheppard and Helen C. Hailes
Green Chemistry 2016 vol. 18(Issue 7) pp:1855-1858
Publication Date(Web):07 Jan 2016
DOI:10.1039/C5GC02935J
One-pot synthetic routes from furfurals to polysubstituted aromatic compounds have been developed in water, without the need for any organic solvents. The reaction proceeds via an uncatalysed, one-pot reaction cascade through formation of a hydrazone derivative, in situ cycloaddition with a dienophile, then aromatisation. A range of substituted phthalimides can be accessed with complete control over the substitution pattern. The reaction was also extended to other dienophiles and the diene 2-furylacrolein. The phthalimide products were further elaborated to produce a variety of polysubstituted benzenes including pharmaceutically relevant compounds.
Co-reporter:Fabiana Subrizi, Max Cárdenas-Fernández, Gary J. Lye, John M. Ward, Paul A. Dalby, Tom D. Sheppard and Helen C. Hailes
Green Chemistry 2016 vol. 18(Issue 10) pp:3158-3165
Publication Date(Web):16 Feb 2016
DOI:10.1039/C5GC02660A
Conversion of biomass using biocatalysis is likely to become a technology that contributes significantly to the future production of chemical building blocks, materials and transport fuels. Here the synthesis of a value-added chemical from L-arabinose, a major component of the carbohydrates in sugar beet pulp (SBP), in a concise and sustainable manner has been investigated. Biocatalytic conversions using transketolase variants have been developed for the efficient, scalable synthesis of a rare naturally occurring ketoheptose, L-gluco-heptulose, from L-arabinose. New active E. coli TK mutants that readily accept L-arabinose were identified using a versatile colorimetric screening assay and the reaction was performed on a preparative scale.
Co-reporter:D. Baud, N. Ladkau, T. S. Moody, J. M. Ward and H. C. Hailes
Chemical Communications 2015 vol. 51(Issue 97) pp:17225-17228
Publication Date(Web):24 Sep 2015
DOI:10.1039/C5CC06817G
A new colorimetric method has been developed to screen transaminases using an inexpensive amine donor. The assay is sensitive, has a low level of background coloration, and can be used to identify and profile transaminase activities against aldehyde and ketone substrates in a high-throughput format. Significantly it is also amendable to solid phase colony screening.
Co-reporter:N. Richter, R. C. Simon, H. Lechner, W. Kroutil, J. M. Ward and H. C. Hailes
Organic & Biomolecular Chemistry 2015 vol. 13(Issue 33) pp:8843-8851
Publication Date(Web):14 Jul 2015
DOI:10.1039/C5OB01204J
The potential of a number of enantiocomplementary ω-transaminases (ω-TAms) in the amination of cyclic ketones has been investigated. After a preliminary screening of several compounds with increasing complexity, different approaches to shift the equilibrium of the reaction to the amine products were studied, and reaction conditions (temperature and pH) optimised. Interestingly, 2-propylamine as an amine donor was tolerated by all five selected ω-TAms, and therefore used in further experiments. Due to the higher conversions observed and interest in chiral amines studies then focused on the amination of α-tetralone and 2-methylcyclohexanone. Both ketones were aminated to give the corresponding amine with at least one of the employed enzymes. Moreover, the amination of 2-methylcyclohexanone was investigated in more detail due to the different stereoselectivities observed with TAms used. The highest yields and stereoselectivities were obtained using the ω-TAm from Chromobacterium violaceum (CV-TAm), producing 2-methylcyclohexylamine with complete stereoselectivity at the (1S)-amine position and up to 24:1 selectivity for the cis:trans [(1S,2R):(1S,2S)] isomer.
Co-reporter:Robert W. Foster;Dr. Christopher J. Tame;Dr. Dejan-Kre&x161;imir Bu&x10d;ar; Helen C. Hailes;Dr. Tom D. Sheppard
Chemistry - A European Journal 2015 Volume 21( Issue 45) pp:15947-15950
Publication Date(Web):
DOI:10.1002/chem.201503510
Abstract
L-Arabinose is an abundant resource available as a waste product of the sugar beet industry. Through use of a hydrazone-based strategy, L-arabinose was selectively dehydrated to form a chiral tetrahydrofuran on a multi-gram scale without the need for protecting groups. This approach was extended to other biomass-derived reducing sugars and the mechanism of the key cyclization investigated. This methodology was applied to the synthesis of a range of functionalized chiral tetrahydrofurans, as well as a formal synthesis of 3R-3-hydroxymuscarine.
Co-reporter:Nina Richter, Robert C. Simon, Wolfgang Kroutil, John M. Ward and Helen C. Hailes
Chemical Communications 2014 vol. 50(Issue 46) pp:6098-6100
Publication Date(Web):19 Feb 2014
DOI:10.1039/C3CC49080G
An efficient and sustainable biocatalytic route for the synthesis of important 17-α-amino steroids has been developed using an ω-transaminase variant from Arthrobacter sp. Optimisation of the reaction conditions facilitated the synthesis of these valuable synthons on a preparative scale, affording excellent isolated yields and stereocontrol.
Co-reporter:S. A. Sanchez-Vazquez, T. D. Sheppard, J. R. G. Evans and H. C. Hailes
RSC Advances 2014 vol. 4(Issue 106) pp:61652-61655
Publication Date(Web):10 Nov 2014
DOI:10.1039/C4RA11558A
Reaction conditions to facilitate the conversion of D-limonene selectively to p,α-dimethylstyrene (DMS) are described, in order to subsequently produce polymeric materials from biomass sourced from food waste. Limonene was dehydrogenated with several palladium catalysts and different solvents and bases, with copper chloride as oxidant at temperatures of 70–120 °C. Reaction conditions were identified using Pd(OAc)2 for the selective formation of only DMS from limonene in 2–5 hours, enabling the facile separation of DMS from unreacted starting material by vacuum distillation.
Co-reporter:Thomas Pesnot;Markus C. Gershater;John M. Ward
Advanced Synthesis & Catalysis 2012 Volume 354( Issue 16) pp:2997-3008
Publication Date(Web):
DOI:10.1002/adsc.201200641
Abstract
The versatility and potential of a norcoclaurine synthase (NCS) from Coptis japonica NCS2 has been investigated, together with the development and application of a novel fluorescence-based high-throughput assay using nearly forty amines/aldehydes. The stereocontrol exerted by CjNCS2 on selected non-natural substrates has been determined, where the tetrahydroisoquinolines (THIAs) were formed as the (1S)-isomer in >95% ee, as observed with the natural product norcoclaurine. Docking calculations involving THIA mechanism intermediates, utilising the reported Thalictrum flavum NCS X-ray crystallographic structure, were carried out and combined with the CjNCS2 screening results to further understand the mode of action of NCS. These findings suggested that in addition to the key active-site residues K122 and E110, D141 is also mechanistically essential for the enzymatic transformation. The exceptional tolerance of NCS towards aldehyde substrates is furthermore supported by our proposed mechanism in which the aldehydes protrude out of the enzymatic pocket.
Co-reporter:James L. Galman, David Steadman, Lisa D. Haigh and Helen C. Hailes
Organic & Biomolecular Chemistry 2012 vol. 10(Issue 13) pp:2621-2628
Publication Date(Web):31 Jan 2012
DOI:10.1039/C2OB06939C
A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate α,α′-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used. Firstly, 13C labelled lithium hydroxypyruvate was synthesised and used to establish where hydroxypyruvate is incorporated in the product. In separate experiments reaction intermediates were also successfully intercepted and structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS. These studies indicated that two mechanisms appear to be operating, one involving the addition of the tertiary amine catalyst to hydroxypyruvate, the other an aldol-based mechanism. Since the first mechanism may enable facial stereodifferentiation in the addition of intermediates to the aldehyde, a preliminary study on the use of chiral catalysts was performed and the first asymmetric organocatalytic synthesis of α,α′-dihydroxy ketones in aqueous media achieved, in up to 50% ee, using a quinine ether catalyst.
Co-reporter:Thomas Pesnot, Markus C. Gershater, John M. Ward and Helen C. Hailes
Chemical Communications 2011 vol. 47(Issue 11) pp:3242-3244
Publication Date(Web):26 Jan 2011
DOI:10.1039/C0CC05282E
A one-pot synthesis of tetrahydroisoquinoline alkaloids in a phosphate buffer has been achieved, and a reaction mechanism proposed. The utilisation of mild reaction conditions readily afforded a range of isoquinolines, including norcoclaurine.
Co-reporter:Valerie G. H. Lafitte, Abil E. Aliev, Elisabetta Greco, Kason Bala, Peter Golding and Helen C. Hailes
New Journal of Chemistry 2011 vol. 35(Issue 7) pp:1522-1527
Publication Date(Web):16 May 2011
DOI:10.1039/C1NJ20162J
A ureidocytosine (UCyt) module with a pendant amine linker at N-1 has been prepared for applications in supramolecular quadruple hydrogen bonded array synthesis. Subsequent conjugation to four amine terminated telechelic polymers led to the formation of oligomeric DDAA arrays, as determined by NMR diffusion measurements, establishing that N-1 as well as N-9 ureidocytosine polymeric arrays can readily be accessed.
Co-reporter:H. C. Hailes
Applied Organometallic Chemistry 2011 Volume 25( Issue 1) pp:
Publication Date(Web):
DOI:10.1002/aoc.1718
No abstract is available for this article.
Co-reporter:Kerry J. Goodworth, Anne-Cécile Hervé, Evangelos Stavropoulos, Gwénaelle Hervé, Isabel Casades, Alison M. Hill, Gordon G. Weingarten, Ricardo E. Tascon, M. Joseph Colston, Helen C. Hailes
Tetrahedron 2011 67(2) pp: 373-382
Publication Date(Web):
DOI:10.1016/j.tet.2010.11.034
Co-reporter:James L. Galman, David Steadman, Sarah Bacon, Phattaraporn Morris, Mark E. B. Smith, John M. Ward, Paul A. Dalby and Helen C. Hailes
Chemical Communications 2010 vol. 46(Issue 40) pp:7608-7610
Publication Date(Web):10 Sep 2010
DOI:10.1039/C0CC02911D
Transketolase mutants have been identified that accept aromatic acceptors with good stereoselectivities, in particular benzaldehyde for which the wild type enzyme showed no activity.
Co-reporter:Armando Cázares, James L. Galman, Lydia G. Crago, Mark E. B. Smith, John Strafford, Leonardo Ríos-Solís, Gary J. Lye, Paul A. Dalby and Helen C. Hailes
Organic & Biomolecular Chemistry 2010 vol. 8(Issue 6) pp:1301-1309
Publication Date(Web):05 Feb 2010
DOI:10.1039/B924144B
Transketolase mutants previously identified for use with the non-phosphorylated aldehyde propanal have been explored with a series of linear and cyclic aliphatic aldehydes, and excellent stereoselectivities observed.
Co-reporter:Elisabetta Greco, Abil E. Aliev, Valerie G. H. Lafitte, Kason Bala, David Duncan, Laura Pilon, Peter Golding and Helen C. Hailes
New Journal of Chemistry 2010 vol. 34(Issue 11) pp:2634-2642
Publication Date(Web):03 Aug 2010
DOI:10.1039/C0NJ00197J
Cytosine modules have been investigated for applications in supramolecular quadruple hydrogen bonded arrays. Notably, the importance of the C-5–H in the formation of unfolded and folded arrays by substitution to C-5–F was established. In addition, the incorporation of different alkyl chain lengths at N-1 and N-9 indicated that longer alkyl chains give rise to more of the unfolded rotamer, with the chain length and degree of unsaturation at N-1 having the major effect. Methyl cytosine modules were also able to readily form hetero-associated Upy–UCyt dimers as efficiently as the hexyl cytosine modules and a polyadipate telechelic polymer was used to prepare cytosine polymers.
Co-reporter:Mark E.B. Smith, Richard M. Gunn, Evelyn Rosivatz, Lok H. Mak, Rüdiger Woscholski, Helen C. Hailes
Bioorganic & Medicinal Chemistry 2010 Volume 18(Issue 14) pp:4917-4927
Publication Date(Web):15 July 2010
DOI:10.1016/j.bmc.2010.06.017
Analogues of the novel inhibitor of the PI3-K/PKB pathway, 2-[5-(2-chloroethyl)-2-acetoxy-benzyl]-4-(2-chloroethyl)-phenyl acetate (E1), have been prepared and preliminary SAR performed. This established that at least one of the chloroethyl para-substituents could be removed or modified and the ability to inhibit PKB/Akt activation retained. Synthetic methodologies were then developed to methylene-linked aryl acetates for use as molecular probes to identify the target of compound E1.Preliminary SAR based on compound E1 was performed, and molecular probes designed and synthesized for applications in studies to identify the target of compound E1.
Co-reporter:Ana Chiva, David E. Williams, Alethea B. Tabor, Helen C. Hailes
Tetrahedron Letters 2010 Volume 51(Issue 20) pp:2720-2723
Publication Date(Web):19 May 2010
DOI:10.1016/j.tetlet.2010.03.040
Several polymeric supports possessing an ester moiety were prepared and a range of enzymes was investigated to hydrolyse the ester linkage and release a signalling group into solution for applications in immunoassays. Pseudomonas lipases were found to most readily cleave the solution-phase analogue and this observation translated well to the corresponding polymeric supports, where the most effective were PEGA resins and the LPOS support PEG-6000.A range of polymeric supports was prepared and investigated for applications in an enzyme cleavable assay.
Co-reporter:Kirsty Smithies, Mark E.B. Smith, Ursula Kaulmann, James L. Galman, John M. Ward, Helen C. Hailes
Tetrahedron: Asymmetry 2009 Volume 20(Issue 5) pp:570-574
Publication Date(Web):25 March 2009
DOI:10.1016/j.tetasy.2009.03.012
The stereoselectivity of a recently isolated ω-transaminase from Chromobacterium violaceum in the amination of 1,3-dihydroxy-1-phenylpropan-2-one has been determined. The enzyme is not enantioselective towards a racemic mixture of 1,3-dihydroxy-1-phenylpropan-2-one but is highly stereoselective forming (2S)-2-amino-1-phenyl-1,3-propanediols in >99% ee.(2S,3R) Ethyl 3-hydroxy-2-(4-nitrophenylsulfonyloxy)-3-phenylpropanoateC17H17NO8SDe ⩾ 70% [(2R,3R)-diastereoisomer present][α]D24=-42.5 (c 3.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)(2R,3R) Ethyl 2-azido-3-hydroxy-3-phenylpropanoateC11H13N3O3De ⩾ 70% [(2S,3R)-diastereoisomer present][α]D24=+9.4 (c 11.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)(1R,2S)-2-Amino-1-phenyl-1,3-propanediolC9H13NO2De ⩾ 70% [(1R,2R)-diastereoisomer present via asymmetric synthesis][α]D20=-14.9 (c 2.0, MeOH)Source of chirality: asymmetric synthesis and biocatalysisAbsolute configuration: (1R,2S)(1S,2S)-2-Acetamido-1-phenylpropane-1,3-diyl diacetateC15H19NO5Ee ⩾ 98% (derivative of commercial sample)[α]D20=+47.1 (c 2.0, CHCl3)Source of chirality: derivative of commercial sample and biocatalysisAbsolute configuration: (1S,2S)(1R,2R)-2-Acetamido-1-phenylpropane-1,3-diyl diacetateC15H19NO5Ee ⩾ 98% (derivative of commercial sample)[α]D20=-61.1 (c 2.0, CHCl3)Source of chirality: derivative of commercial sampleAbsolute configuration: (1R,2R)(1R,2S)-2-Acetamido-1-phenylpropane-1,3-diyl diacetateC15H19NO5De ⩾ 70% [(1R,2R)-diastereoisomer present via asymmetric synthesis][α]D20=-19.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesis and biocatalysisAbsolute configuration: (1R,2S)
Co-reporter:James L. Galman, Helen C. Hailes
Tetrahedron: Asymmetry 2009 Volume 20(Issue 15) pp:1828-1831
Publication Date(Web):12 August 2009
DOI:10.1016/j.tetasy.2009.07.023
The enantiomeric ratio and absolute configuration of products of the transketolase reaction are typically determined by comparison of the specific rotation or derivatisation and HPLC or GC. A Mosher’s ester method has been developed via ester formation at the primary alcohol C-1 which can be used to determine the stereoselectivity of the reaction, as well as the absolute configuration of the product at C-3.(2R,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-2′-oxo-pentyl esterC15H17F3O5De = 55% [(2R,3′S)-major isomer, (2R,3′R) present][α]D20=+13.3 (c 0.15, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2R,3′S)(2S,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-2′-oxo-pentyl esterC15H17F3O5De = 55% [(2S,3′S)-major isomer, (2S,3′R) present][α]D20=-37.0 (c 0.1, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2S,3′S)(2R,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′,4′-dihydroxy-2′-oxo-butyl esterC14H15F3O6De = >95% (2R,3′S)[α]D20=+10.2 (c 0.4, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2R,3′S)(2S,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′,4′-dihydroxy-2′-oxo-butyl esterC14H15F3O6De = >95% (2S,3′S)[α]D20=-14.4 (c 0.5, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2S,3′S)(2R,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-4′-methoxy-2′-oxo-butyl esterC15H17F3O6De = 57% [(2R,3′S)-major isomer, (2R,3′R) present][α]D20=+23.2 (c 0.25, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2R,3′S)(2S,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-4′-methoxy-2′-oxo-butyl esterC15H17F3O6De = 57% [(2S,3′S)-major isomer, (2S,3′R) present][α]D20=-10.6 (c 0.25, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2S,3′S)(3S)-1,3-Dihydroxy-4-methoxybutan-2-oneC5H10O4Ee = 57% [(3S)-major isomer][α]D20=+2.0 (c 2.0, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (3S)
Co-reporter:Mark E.B. Smith;EdwardG. Hibbert;AlexerB. Jones;PaulA. Dalby;HelenC. Hailes
Advanced Synthesis & Catalysis 2008 Volume 350( Issue 16) pp:2631-2638
Publication Date(Web):
DOI:10.1002/adsc.200800489
Abstract
Chiral auxiliary methodology and chiral assays have been developed to establish the enantiomeric purities of erythrulose and 1,3-dihydroxypentan-2-one generated using wild-type (WT) Escherichia coli transketolase (TK). L-Erythrulose was formed in 95% ee and (3S)-1,3-dihydroxypentan-2-one in 58% ee. Since the latter compound was formed in moderate ee, TK libraries were screened to identify higher performing mutants. A colorimetric screen and chiral assay were successfully applied to a 96-well format, and new active TK mutants were identified, which gave 1,3-dihydroxypentan-2-one in high stereoselectivities. Remarkably, active-site single-point mutants were identified that were able to both enhance and reverse the stereoselectivity of TK.
Co-reporter:Christopher A. Hurley, John B. Wong, Jimmy Ho, Michele Writer, Scott A. Irvine, M. Jayne Lawrence, Stephen L. Hart, Alethea B. Tabor and Helen C. Hailes
Organic & Biomolecular Chemistry 2008 vol. 6(Issue 14) pp:2554-2559
Publication Date(Web):30 May 2008
DOI:10.1039/B719702K
A range of monocationic and dicationic dioxyalkylglycerol cytofectins have been synthesised possessing methylene and short n-ethylene glycol spacers. The monocationic compounds were found to be effective in transfections when formulated as lipopolyplexes with peptide and DNA components, in particular with shorter PEG head groups which may have less effect on peptide targeting in the ternary complex.
Co-reporter:John B. Wong, Stephanie Grosse, Alethea B. Tabor, Stephen L. Hart and Helen C. Hailes
Molecular BioSystems 2008 vol. 4(Issue 6) pp:532-541
Publication Date(Web):15 Apr 2008
DOI:10.1039/B719782A
A novel class of pH-sensitive PEG lipids bearing acid-cleavable acetal linkages and short PEG chains have been synthesised and used in ternary vector formulations. The cleavage pH was influenced by structural components including the terminal PEG moiety and spacer length.
Co-reporter:Valérie G. H. Lafitte, Abil E. Aliev, Peter N. Horton, Michael B. Hursthouse and Helen C. Hailes
Chemical Communications 2006 (Issue 20) pp:2173-2175
Publication Date(Web):20 Apr 2006
DOI:10.1039/B600459H
Highly stable cyclic dimers have been assembled through a combination of non-covalent interactions, including multiple hydrogen bonding, parallel stacking and hydrophobic shielding.
Co-reporter:Mark E. B. Smith;Kirsty Smithies;Tarik Senussi;Paul A. Dalby
European Journal of Organic Chemistry 2006 Volume 2006(Issue 5) pp:
Publication Date(Web):24 JAN 2006
DOI:10.1002/ejoc.200500986
Although the biocatalytic formation of acyclic α,α′-dihydroxy ketones by transketolase is well documented in the literature, there is currently no one-pot chemical synthesis of these dihydroxy ketones available. Here, we report preliminary results of an atom-efficient one-pot synthesis of α,α′-dihydroxy ketones in water by a mimic of the transketolase reaction. The formation of a quaternary ammonium enolate is postulated in this tertiary-amine-mediated carbon–carbon bond-forming reaction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Co-reporter:Gwénaëlle Hervé, Dirk Uwe Hahn, Anne-Cécile Hervé, Kerry J. Goodworth, Alison M. Hill and Helen C. Hailes
Organic & Biomolecular Chemistry 2003 vol. 1(Issue 2) pp:427-435
Publication Date(Web):19 Dec 2002
DOI:10.1039/B208649M
Methodologies to access water soluble large ringed calixarenes in good yield using efficient synthetic procedures have been investigated. Symmetrical partial functionalisations at the lower rim are described using activated [n]ethylene glycol chains and the addition behaviour contrasted with that of bromoalkanenitriles which proceeds with no observed regioselectivity. Full functionalisations of the calixarenes bearing hydrophilic groups are then investigated and a two-step procedure established which appears to be generally applicable for the addition of different [n]ethylene glycol chains. Furthermore, difunctionalisation under different reaction conditions are described. Throughout, strategies for the characterisation of these high mass compounds are outlined.
Co-reporter:Maria F. Villegas-Torres, R. Julio Martinez-Torres, Armando Cázares-Körner, Helen Hailes, Frank Baganz, John Ward
Enzyme and Microbial Technology (December 2015) Volume 81() pp:23-30
Publication Date(Web):1 December 2015
DOI:10.1016/j.enzmictec.2015.07.003
•A double-recycling cascade for the synthesis of (2S,3R)-2-amino-1,3,4-butanetriol.•An α-transaminase with a high affinity for a serine donor and keto acid acceptors.•Two ω-transaminases with serine donor activity to make chiral amino alcohols.•Transaminase cascades to make hydroxypyruvate for transketolase reactions.Chiral amino alcohols are structural motifs present in sphingolipids, antibiotics, and antiviral glycosidase inhibitors. Their chemical synthesis presents several challenges in establishing at least two chiral centres. Here a de novo metabolic pathway using a transketolase enzyme coupled with a transaminase enzyme has been assembled. To synthesise this motif one of the strategies to obtain high conversions from the transaminase/transketolase cascade is the use of hydroxypyruvate (HPA) as a two-carbon donor for the transketolase reaction; although commercially available it is relatively expensive limiting application of the pathway on an industrial scale. Alternately, HPA can be synthesised but this introduces a further synthetic step. In this study two different biocatalytic strategies were developed for the synthesis of (2S,3R)-2-amino-1,3,4-butanetriol (ABT) without adding HPA into the reaction. Firstly, a sequential cascade of three enzymatic steps (two transaminases and one transketolase) for the synthesis of ABT from serine, pyruvate and glycolaldehyde as substrates. Secondly, a two-step recycling cascade where serine is used as donor to aminate erythrulose (catalysed by a transketolase) for the simultaneous synthesis of ABT and HPA. In order to test the novel pathways, three new transaminases are described, two ω-transaminases able to accept a broad range of amine acceptors with serine as amine donor; and an α-transaminase, which showed high affinity towards serine (KM: 18 mM) using pyruvate as amine acceptor. After implementation of the above enzymes in the biocatalytic pathways proposed in this paper, the two-step recycling pathway was found to be the most promising for its integration with E. coli metabolism. It was more efficient (10-fold higher conversion), more sustainable and cost-effective (use of low cost natural substrates and only two enzymes), and the reaction could be performed in a one-pot system.
Co-reporter:Christopher A. Hurley, John B. Wong, Jimmy Ho, Michele Writer, Scott A. Irvine, M. Jayne Lawrence, Stephen L. Hart, Alethea B. Tabor and Helen C. Hailes
Organic & Biomolecular Chemistry 2008 - vol. 6(Issue 14) pp:NaN2559-2559
Publication Date(Web):2008/05/30
DOI:10.1039/B719702K
A range of monocationic and dicationic dioxyalkylglycerol cytofectins have been synthesised possessing methylene and short n-ethylene glycol spacers. The monocationic compounds were found to be effective in transfections when formulated as lipopolyplexes with peptide and DNA components, in particular with shorter PEG head groups which may have less effect on peptide targeting in the ternary complex.
Co-reporter:James L. Galman, David Steadman, Lisa D. Haigh and Helen C. Hailes
Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 13) pp:NaN2628-2628
Publication Date(Web):2012/01/31
DOI:10.1039/C2OB06939C
A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate α,α′-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used. Firstly, 13C labelled lithium hydroxypyruvate was synthesised and used to establish where hydroxypyruvate is incorporated in the product. In separate experiments reaction intermediates were also successfully intercepted and structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS. These studies indicated that two mechanisms appear to be operating, one involving the addition of the tertiary amine catalyst to hydroxypyruvate, the other an aldol-based mechanism. Since the first mechanism may enable facial stereodifferentiation in the addition of intermediates to the aldehyde, a preliminary study on the use of chiral catalysts was performed and the first asymmetric organocatalytic synthesis of α,α′-dihydroxy ketones in aqueous media achieved, in up to 50% ee, using a quinine ether catalyst.
Co-reporter:Armando Cázares, James L. Galman, Lydia G. Crago, Mark E. B. Smith, John Strafford, Leonardo Ríos-Solís, Gary J. Lye, Paul A. Dalby and Helen C. Hailes
Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 6) pp:NaN1309-1309
Publication Date(Web):2010/02/05
DOI:10.1039/B924144B
Transketolase mutants previously identified for use with the non-phosphorylated aldehyde propanal have been explored with a series of linear and cyclic aliphatic aldehydes, and excellent stereoselectivities observed.
Co-reporter:James L. Galman, David Steadman, Sarah Bacon, Phattaraporn Morris, Mark E. B. Smith, John M. Ward, Paul A. Dalby and Helen C. Hailes
Chemical Communications 2010 - vol. 46(Issue 40) pp:NaN7610-7610
Publication Date(Web):2010/09/10
DOI:10.1039/C0CC02911D
Transketolase mutants have been identified that accept aromatic acceptors with good stereoselectivities, in particular benzaldehyde for which the wild type enzyme showed no activity.
Co-reporter:Thomas Pesnot, Markus C. Gershater, John M. Ward and Helen C. Hailes
Chemical Communications 2011 - vol. 47(Issue 11) pp:NaN3244-3244
Publication Date(Web):2011/01/26
DOI:10.1039/C0CC05282E
A one-pot synthesis of tetrahydroisoquinoline alkaloids in a phosphate buffer has been achieved, and a reaction mechanism proposed. The utilisation of mild reaction conditions readily afforded a range of isoquinolines, including norcoclaurine.
Co-reporter:Nina Richter, Robert C. Simon, Wolfgang Kroutil, John M. Ward and Helen C. Hailes
Chemical Communications 2014 - vol. 50(Issue 46) pp:NaN6100-6100
Publication Date(Web):2014/02/19
DOI:10.1039/C3CC49080G
An efficient and sustainable biocatalytic route for the synthesis of important 17-α-amino steroids has been developed using an ω-transaminase variant from Arthrobacter sp. Optimisation of the reaction conditions facilitated the synthesis of these valuable synthons on a preparative scale, affording excellent isolated yields and stereocontrol.
Co-reporter:N. Richter, R. C. Simon, H. Lechner, W. Kroutil, J. M. Ward and H. C. Hailes
Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 33) pp:NaN8851-8851
Publication Date(Web):2015/07/14
DOI:10.1039/C5OB01204J
The potential of a number of enantiocomplementary ω-transaminases (ω-TAms) in the amination of cyclic ketones has been investigated. After a preliminary screening of several compounds with increasing complexity, different approaches to shift the equilibrium of the reaction to the amine products were studied, and reaction conditions (temperature and pH) optimised. Interestingly, 2-propylamine as an amine donor was tolerated by all five selected ω-TAms, and therefore used in further experiments. Due to the higher conversions observed and interest in chiral amines studies then focused on the amination of α-tetralone and 2-methylcyclohexanone. Both ketones were aminated to give the corresponding amine with at least one of the employed enzymes. Moreover, the amination of 2-methylcyclohexanone was investigated in more detail due to the different stereoselectivities observed with TAms used. The highest yields and stereoselectivities were obtained using the ω-TAm from Chromobacterium violaceum (CV-TAm), producing 2-methylcyclohexylamine with complete stereoselectivity at the (1S)-amine position and up to 24:1 selectivity for the cis:trans [(1S,2R):(1S,2S)] isomer.
Co-reporter:D. Baud, N. Ladkau, T. S. Moody, J. M. Ward and H. C. Hailes
Chemical Communications 2015 - vol. 51(Issue 97) pp:NaN17228-17228
Publication Date(Web):2015/09/24
DOI:10.1039/C5CC06817G
A new colorimetric method has been developed to screen transaminases using an inexpensive amine donor. The assay is sensitive, has a low level of background coloration, and can be used to identify and profile transaminase activities against aldehyde and ketone substrates in a high-throughput format. Significantly it is also amendable to solid phase colony screening.
![Nonacyclo[43.3.1.13,7.19,13.115,19.121,25.127,31.133,37.139,43]hexapentaconta-1(49),3,5,7(56),9,11,13(55),15,17,19(54),21,23,25(53),27,29,31(52),33,35,37(51),39,41,43(50),45,47-tetracosaene-49,50,51,52,53,54,55,56-octol, 5,11,17,23,29,35,41,47-octakis(1,1-dimethylethyl)-, 49,50,51,52,53,54,55,56-octaacetate](/data/chemimg/3724200/78077-33-5.png)
![Nonacyclo[43.3.1.13,7.19,13.115,19.121,25.127,31.133,37.139,43]hexapentaconta-1(49),3,5,7(56),9,11,13(55),15,17,19(54),21,23,25(53),27,29,31(52),33,35,37(51),39,41,43(50),45,47-tetracosaene-49,50,51,52,53,54,55,56-octol, 5,11,17,23,29,35,41,47-octakis(1,1-dimethylethyl)-, 49,50,51,52,53,54,55,56-octaacetate](/data/chemimg/3724200/78077-33-5_b.png)
![Heptacyclo[31.3.1.13,7.19,13.115,19.121,25.127,31]dotetraconta-1(37),3,5,7(42),9,11,13(41),15,17,19(40),21,23,25(39),27,29,31(38),33,35-octadecaene-37,38,39,40,41,42-hexol, 5,11,17,23,29,35-hexaphenyl-](/data/chemimg/3724200/92887-22-4.png)
![Heptacyclo[31.3.1.13,7.19,13.115,19.121,25.127,31]dotetraconta-1(37),3,5,7(42),9,11,13(41),15,17,19(40),21,23,25(39),27,29,31(38),33,35-octadecaene-37,38,39,40,41,42-hexol, 5,11,17,23,29,35-hexaphenyl-](/data/chemimg/3724200/92887-22-4_b.png)
![Nonacyclo[43.3.1.13,7.19,13.115,19.121,25.127,31.133,37.139,43]hexapentaconta-1(49),3,5,7(56),9,11,13(55),15,17,19(54),21,23,25(53),27,29,31(52),33,35,37(51),39,41,43(50),45,47-tetracosaene-49,50,51,52,53,54,55,56-octol, 5,11,17,23,29,35,41,47-octaphenyl-](/data/chemimg/3724200/92887-20-2.png)
![Nonacyclo[43.3.1.13,7.19,13.115,19.121,25.127,31.133,37.139,43]hexapentaconta-1(49),3,5,7(56),9,11,13(55),15,17,19(54),21,23,25(53),27,29,31(52),33,35,37(51),39,41,43(50),45,47-tetracosaene-49,50,51,52,53,54,55,56-octol, 5,11,17,23,29,35,41,47-octaphenyl-](/data/chemimg/3724200/92887-20-2_b.png)
![Benzaldehyde, 2-[[(2E)-3-phenyl-2-propenyl]oxy]-, oxime](http://img.cochemist.com/ccimg/876700/876609-85-7.png)
![Benzaldehyde, 2-[[(2E)-3-phenyl-2-propenyl]oxy]-, oxime](http://img.cochemist.com/ccimg/876700/876609-85-7_b.png)
![Benzaldehyde, 2-[2-(2-propenyloxy)ethoxy]-, oxime](http://img.cochemist.com/ccimg/876700/876609-93-7.png)
![Benzaldehyde, 2-[2-(2-propenyloxy)ethoxy]-, oxime](http://img.cochemist.com/ccimg/876700/876609-93-7_b.png)
![1-Propanamine, 2,3-bis[(11Z)-11-hexadecenyloxy]-N,N-dimethyl-](http://img.cochemist.com/ccimg/868600/868594-36-9.png)
![1-Propanamine, 2,3-bis[(11Z)-11-hexadecenyloxy]-N,N-dimethyl-](http://img.cochemist.com/ccimg/868600/868594-36-9_b.png)
![Benzaldehyde, 2-[[(2E)-3-phenyl-2-propenyl]amino]-](http://img.cochemist.com/ccimg/876700/876609-91-5.png)
![Benzaldehyde, 2-[[(2E)-3-phenyl-2-propenyl]amino]-](http://img.cochemist.com/ccimg/876700/876609-91-5_b.png)
![Pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-25,26,27,28-tetrol, 5,11,17,23-tetraphenyl-](/data/chemimg/3724200/60705-63-7.png)
![Pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-25,26,27,28-tetrol, 5,11,17,23-tetraphenyl-](/data/chemimg/3724200/60705-63-7_b.png)
![Benzeneacetyl chloride, 4-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-](http://img.cochemist.com/ccimg/850200/850148-61-7.png)
![Benzeneacetyl chloride, 4-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-](http://img.cochemist.com/ccimg/850200/850148-61-7_b.png)
![Acetyl azide, [2-(2-methoxyethoxy)ethoxy]-](http://img.cochemist.com/ccimg/850200/850148-59-3.png)
![Acetyl azide, [2-(2-methoxyethoxy)ethoxy]-](http://img.cochemist.com/ccimg/850200/850148-59-3_b.png)
![Ethane, 1-[2-(isocyanatomethoxy)ethoxy]-2-methoxy-](http://img.cochemist.com/ccimg/850200/850148-53-7.png)
![Ethane, 1-[2-(isocyanatomethoxy)ethoxy]-2-methoxy-](http://img.cochemist.com/ccimg/850200/850148-53-7_b.png)
![Urea, N-[1,4-dihydro-6-(4-nitrophenyl)-4-oxo-2-pyrimidinyl]-N'-hexyl-](http://img.cochemist.com/ccimg/850200/850148-51-5.png)
![Urea, N-[1,4-dihydro-6-(4-nitrophenyl)-4-oxo-2-pyrimidinyl]-N'-hexyl-](http://img.cochemist.com/ccimg/850200/850148-51-5_b.png)
![1-Propanamine, 2,3-bis[(9Z)-9-octadecenyloxy]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-69-1.png)
![1-Propanamine, 2,3-bis[(9Z)-9-octadecenyloxy]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-69-1_b.png)
![1-Propanamine, 2,3-bis[(11Z)-11-tetradecenyloxy]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-65-7.png)
![1-Propanamine, 2,3-bis[(11Z)-11-tetradecenyloxy]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-65-7_b.png)
![2-Propanone, 1-[(1R,2S)-3-hydroxy-2-(2Z)-2-pentenylcyclopentyl]-, rel-](http://img.cochemist.com/ccimg/403700/403664-51-7.png)
![2-Propanone, 1-[(1R,2S)-3-hydroxy-2-(2Z)-2-pentenylcyclopentyl]-, rel-](http://img.cochemist.com/ccimg/403700/403664-51-7_b.png)
![1-Propanamine, 2,3-bis[(9Z)-9-octadecenyloxy]-](http://img.cochemist.com/ccimg/396800/396728-08-8.png)
![1-Propanamine, 2,3-bis[(9Z)-9-octadecenyloxy]-](http://img.cochemist.com/ccimg/396800/396728-08-8_b.png)
![1,2-Propanediol, 3-[(phenylmethylene)amino]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-75-9.png)
![1,2-Propanediol, 3-[(phenylmethylene)amino]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-75-9_b.png)
![ETHANOL, 2-[2-(2-BROMOETHOXY)ETHOXY]-](http://img.cochemist.com/ccimg/57700/57641-67-5.png)
![ETHANOL, 2-[2-(2-BROMOETHOXY)ETHOXY]-](http://img.cochemist.com/ccimg/57700/57641-67-5_b.png)
![BENZENEACETYL AZIDE, 4-[2-[2-(2-METHOXYETHOXY)ETHOXY]ETHOXY]-](http://img.cochemist.com/ccimg/850200/850148-62-8.png)
![BENZENEACETYL AZIDE, 4-[2-[2-(2-METHOXYETHOXY)ETHOXY]ETHOXY]-](http://img.cochemist.com/ccimg/850200/850148-62-8_b.png)
![BENZALDEHYDE, 2-[2-(2-PROPENYLOXY)ETHOXY]-](http://img.cochemist.com/ccimg/876700/876609-92-6.png)
![BENZALDEHYDE, 2-[2-(2-PROPENYLOXY)ETHOXY]-](http://img.cochemist.com/ccimg/876700/876609-92-6_b.png)
![UREA, N-[6-(4-AMINOPHENYL)-1,4-DIHYDRO-4-OXO-2-PYRIMIDINYL]-N'-HEXYL-](http://img.cochemist.com/ccimg/850200/850148-50-4.png)
![UREA, N-[6-(4-AMINOPHENYL)-1,4-DIHYDRO-4-OXO-2-PYRIMIDINYL]-N'-HEXYL-](http://img.cochemist.com/ccimg/850200/850148-50-4_b.png)
![BENZENEACETIC ACID, 4-[2-[2-(2-METHOXYETHOXY)ETHOXY]ETHOXY]-](http://img.cochemist.com/ccimg/850200/850148-60-6.png)
![BENZENEACETIC ACID, 4-[2-[2-(2-METHOXYETHOXY)ETHOXY]ETHOXY]-](http://img.cochemist.com/ccimg/850200/850148-60-6_b.png)
![1-PROPANAMINE, N,N-DIMETHYL-2,3-BIS[(9Z)-9-OCTADECENYLOXY]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-78-2.png)
![1-PROPANAMINE, N,N-DIMETHYL-2,3-BIS[(9Z)-9-OCTADECENYLOXY]-, (2R)-](http://img.cochemist.com/ccimg/666300/666234-78-2_b.png)
![1-PROPANAMINE, 2,3-BIS[(11Z)-11-TETRADECENYLOXY]-, (2S)-](http://img.cochemist.com/ccimg/666300/666234-66-8.png)
![1-PROPANAMINE, 2,3-BIS[(11Z)-11-TETRADECENYLOXY]-, (2S)-](http://img.cochemist.com/ccimg/666300/666234-66-8_b.png)
![1-PROPANAMINE, 2,3-BIS[(11Z)-11-HEXADECENYLOXY]-N,N-DIMETHYL-, (2S)-](http://img.cochemist.com/ccimg/666300/666234-80-6.png)
![1-PROPANAMINE, 2,3-BIS[(11Z)-11-HEXADECENYLOXY]-N,N-DIMETHYL-, (2S)-](http://img.cochemist.com/ccimg/666300/666234-80-6_b.png)
![BENZENEMETHANOL, 2-[[(2E)-3-PHENYL-2-PROPENYL]AMINO]-](http://img.cochemist.com/ccimg/876700/876609-90-4.png)
![BENZENEMETHANOL, 2-[[(2E)-3-PHENYL-2-PROPENYL]AMINO]-](http://img.cochemist.com/ccimg/876700/876609-90-4_b.png)
![BENZALDEHYDE, 2-[[(2E)-3-PHENYL-2-PROPENYL]AMINO]-, OXIME](http://img.cochemist.com/ccimg/876700/876609-86-8.png)
![BENZALDEHYDE, 2-[[(2E)-3-PHENYL-2-PROPENYL]AMINO]-, OXIME](http://img.cochemist.com/ccimg/876700/876609-86-8_b.png)
![NONACYCLO[43.3.1.13,7.19,13.115,19.121,25.127,31.133,37.139,43]HEXAPENTACONTA-1(49),3,5,7(56),9,11,13(55),15,17,19(54),21,23,25(53),27,29,31(52),33,35,37(51),39,41,43(50),45,47-TETRACOSAENE-49,50,51,52,53,54,55,56-OCTOL, 5,11,17,23,29,35,41,47-OCTAKIS(1,1,3,3-TETRAMETHYLBUTYL)-](http://img.cochemist.com/ccimg/82500/82452-92-4.png)
![NONACYCLO[43.3.1.13,7.19,13.115,19.121,25.127,31.133,37.139,43]HEXAPENTACONTA-1(49),3,5,7(56),9,11,13(55),15,17,19(54),21,23,25(53),27,29,31(52),33,35,37(51),39,41,43(50),45,47-TETRACOSAENE-49,50,51,52,53,54,55,56-OCTOL, 5,11,17,23,29,35,41,47-OCTAKIS(1,1,3,3-TETRAMETHYLBUTYL)-](http://img.cochemist.com/ccimg/82500/82452-92-4_b.png)
![1-PROPANAMINE, 2,3-BIS[(9Z)-9-OCTADECENYLOXY]-, (2S)-](http://img.cochemist.com/ccimg/666300/666234-70-4.png)
![1-PROPANAMINE, 2,3-BIS[(9Z)-9-OCTADECENYLOXY]-, (2S)-](http://img.cochemist.com/ccimg/666300/666234-70-4_b.png)
![2-[2-[2-(2-Bromoethoxy)ethoxy]ethoxy]-ethanol](http://img.cochemist.com/ccimg/85200/85141-94-2.png)
![2-[2-[2-(2-Bromoethoxy)ethoxy]ethoxy]-ethanol](http://img.cochemist.com/ccimg/85200/85141-94-2_b.png)
amine](http://img.cochemist.com/ccimg/114200/114105-51-0.png)
amine](http://img.cochemist.com/ccimg/114200/114105-51-0_b.png)
![Carbamic acid, [6-[(methylsulfonyl)oxy]hexyl]-, phenylmethyl ester](http://img.cochemist.com/ccimg/76000/75937-26-7.png)
![Carbamic acid, [6-[(methylsulfonyl)oxy]hexyl]-, phenylmethyl ester](http://img.cochemist.com/ccimg/76000/75937-26-7_b.png)
![1,3-Propanediol, 2,2-bis[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-](http://img.cochemist.com/ccimg/843700/843646-97-9.png)
![1,3-Propanediol, 2,2-bis[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-](http://img.cochemist.com/ccimg/843700/843646-97-9_b.png)
![4H-Imidazol-4-one,3,5-dihydro-5-[(4-hydroxyphenyl)methylene]-2,3-dimethyl-](http://img.cochemist.com/ccimg/184400/184302-39-4.png)
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![Benzenamine, 2-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-](http://img.cochemist.com/ccimg/68900/68847-33-6.png)
![Benzenamine, 2-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-](http://img.cochemist.com/ccimg/68900/68847-33-6_b.png)
![9-Octadecenoic acid(9Z)-, 1,1'-[1-[[[(2-aminoethoxy)hydroxyphosphinyl]oxy]methyl]-1,2-ethanediyl]ester](http://img.cochemist.com/ccimg/2500/2462-63-7.png)
![9-Octadecenoic acid(9Z)-, 1,1'-[1-[[[(2-aminoethoxy)hydroxyphosphinyl]oxy]methyl]-1,2-ethanediyl]ester](http://img.cochemist.com/ccimg/2500/2462-63-7_b.png)
![Acetyl chloride, [2-(2-methoxyethoxy)ethoxy]-](http://img.cochemist.com/ccimg/63900/63881-16-3.png)
![Acetyl chloride, [2-(2-methoxyethoxy)ethoxy]-](http://img.cochemist.com/ccimg/63900/63881-16-3_b.png)
![Hexanoic acid, 6-[(tetrahydro-2H-pyran-2-yl)oxy]-](http://img.cochemist.com/ccimg/32500/32437-88-0.png)
![Hexanoic acid, 6-[(tetrahydro-2H-pyran-2-yl)oxy]-](http://img.cochemist.com/ccimg/32500/32437-88-0_b.png)
![6,7-Isoquinolinediol, 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-,(1S)-](http://img.cochemist.com/ccimg/22700/22672-77-1.png)
![6,7-Isoquinolinediol, 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-,(1S)-](http://img.cochemist.com/ccimg/22700/22672-77-1_b.png)
![[3-[HYDROXY(2-HYDROXYETHOXY)PHOSPHORYL]OXY-2-[(E)-OCTADEC-9-ENOYL]OXYPROPYL] (E)-OCTADEC-9-ENOATE](http://img.cochemist.com/ccimg/76400/76391-83-8.png)
![[3-[HYDROXY(2-HYDROXYETHOXY)PHOSPHORYL]OXY-2-[(E)-OCTADEC-9-ENOYL]OXYPROPYL] (E)-OCTADEC-9-ENOATE](http://img.cochemist.com/ccimg/76400/76391-83-8_b.png)
![O-(2-Aminoethyl)-O’-[2-(Boc-amino)ethyl]tetraethylene Glycol](http://img.cochemist.com/ccimg/189300/189209-27-6.png)
![O-(2-Aminoethyl)-O’-[2-(Boc-amino)ethyl]tetraethylene Glycol](http://img.cochemist.com/ccimg/189300/189209-27-6_b.png)
![Ruthenium,chloro[(1,2,5,6-h)-1,5-cyclooctadiene][(1,2,3,4,5-h)-1,2,3,4,5-pentamethyl-2,4-cyclopentadien-1-yl]-](http://img.cochemist.com/ccimg/92400/92390-26-6.png)
![Ruthenium,chloro[(1,2,5,6-h)-1,5-cyclooctadiene][(1,2,3,4,5-h)-1,2,3,4,5-pentamethyl-2,4-cyclopentadien-1-yl]-](http://img.cochemist.com/ccimg/92400/92390-26-6_b.png)
![METHANESULFONIC ACID;2-[2-(2-METHOXYETHOXY)ETHOXY]ETHANOL](http://img.cochemist.com/ccimg/74700/74654-05-0.png)
![METHANESULFONIC ACID;2-[2-(2-METHOXYETHOXY)ETHOXY]ETHANOL](http://img.cochemist.com/ccimg/74700/74654-05-0_b.png)
![2-(2-[2-(2-HYDROXY-ETHOXY)-ETHOXY]-ETHYL)-ISOINDOLE-1,3-DIONE](http://img.cochemist.com/ccimg/75100/75001-08-0.png)
![2-(2-[2-(2-HYDROXY-ETHOXY)-ETHOXY]-ETHYL)-ISOINDOLE-1,3-DIONE](http://img.cochemist.com/ccimg/75100/75001-08-0_b.png)
![1-(2-BROMOETHOXY)-2-[2-(2-BROMOETHOXY)ETHOXY]ETHANE](http://img.cochemist.com/ccimg/31300/31255-26-2.png)
![1-(2-BROMOETHOXY)-2-[2-(2-BROMOETHOXY)ETHOXY]ETHANE](http://img.cochemist.com/ccimg/31300/31255-26-2_b.png)
![Ethanol, 2-[2-[2-(triphenylmethoxy)ethoxy]ethoxy]-](http://img.cochemist.com/ccimg/133700/133699-09-9.png)
![Ethanol, 2-[2-[2-(triphenylmethoxy)ethoxy]ethoxy]-](http://img.cochemist.com/ccimg/133700/133699-09-9_b.png)
![4-[(2E)-3-CHLORO-2-PROPEN-1-YL]-1-DODECANAMINE](http://img.cochemist.com/ccimg/400/300-54-9.png)
![4-[(2E)-3-CHLORO-2-PROPEN-1-YL]-1-DODECANAMINE](http://img.cochemist.com/ccimg/400/300-54-9_b.png)
![2-{[(2E)-3-Phenylprop-2-enyl]oxy}benzaldehyde](http://img.cochemist.com/ccimg/28900/28809-06-5.png)
![2-{[(2E)-3-Phenylprop-2-enyl]oxy}benzaldehyde](http://img.cochemist.com/ccimg/28900/28809-06-5_b.png)
![9-Octadecenoic acid(9Z)-,1,1'-[(1R)-1-[[[(2-aminoethoxy)hydroxyphosphinyl]oxy]methyl]-1,2-ethanediyl]ester](http://img.cochemist.com/ccimg/4100/4004-05-1.png)
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![1H-Pyrrole-2,5-dione,1-[(4-methylphenyl)methyl]-](http://img.cochemist.com/ccimg/42900/42867-34-5.png)
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![4,7,11,14,18,21-Hexaazatetracosanediamide,N1,N24-bis(2-aminoethyl)-4,21-bis[3-[(2-aminoethyl)amino]-3-oxopropyl]-11,14-bis[3-[[2-[bis[3-[(2-aminoethyl)amino]-3-oxopropyl]amino]ethyl]amino]-3-oxopropyl]-8,17-dioxo-](http://img.cochemist.com/ccimg/143000/142986-44-5_b.png)
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