An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
A new method for the discovery of amphiphiles by using high-throughput (HT) methods to synthesise... more A new method for the discovery of amphiphiles by using high-throughput (HT) methods to synthesise and characterise a library of galactose-and glucose-containing amphiphilic compounds is presented. The copper-catalysed azide-alkyne cycloaddition (CuAAC) "click" reaction between azide-tethered simple sugars and alkyne-substituted hydrophobic tails was employed to synthesise a library of compounds with systematic variations in chain length and unsaturation in a 24-vial array format. The liquid-crystalline phase behaviour was characterised in a HT manner by using synchrotron small-angle X-ray scattering (SSAXS). The observed structural variation with respect to chain parameters, including chain length and degree of unsaturation, is discussed, as well as hydration effects and degree of hydrogen bonding between head groups. The validity of our HT screening approach was verified by resynthesising a shortchain glucose amphiphile. A separate phase analysis of this compound confirmed the presence of numerous lyotropic liquid-crystalline phases.
Beilstein Journal of Organic Chemistry, Jul 10, 2014
Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystal... more Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the coppercatalysed azide-alkyne cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.
Acta Crystallographica Section C-crystal Structure Communications, Nov 18, 2009
The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxid... more The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxide, C(9)H(15)NO(3)S, was found to crystallize with two molecules in the asymmetric unit. The structure was solved in both the approximately orthogonal and the oblique settings of space group No. 14, viz. P2(1)/n and P2(1)/c, respectively. A comparison of these results clearly displayed an increase in the correlation between coordinates in the ac plane for the oblique cell. The increase in the corresponding covariances makes a significant contribution to the standard uncertainties of derived parameters, e.g. bond lengths. Since there is yet no CIF definition for the full variance-covariance matrix, there are clear advantages to reporting the structure in the nonstandard space-group setting.
The Intramolecular Amination of Allenes.-Rhodium-bound nitrenoids are trapped by tethered allenes... more The Intramolecular Amination of Allenes.-Rhodium-bound nitrenoids are trapped by tethered allenes generating a variety of structures such as aminocyclopropanes (III) and methylene aziridines (IX). The aminocyclopropanes undergo substitution of the acetoxy group by a variety of nucleophiles, cf. formation of products (X) and (XII).-(FEAST, G. C.;
Colloids and Surfaces B: Biointerfaces, Mar 1, 2017
The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high... more The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using highthroughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200 g mL −1 .
Single crystal X-ray diffraction data were obtained using a Nonius Kappa-CCD area detector diffra... more Single crystal X-ray diffraction data were obtained using a Nonius Kappa-CCD area detector diffractometer, with graphite-monochromated Mo-K! radiation (! = 0.71073 Å) at 150 K. Cell parameters and intensity data were processed using the DENZO-SMN package 1 and reflection intensities were corrected for absorption effects by the multi-scan method, based on multiple scans of identical and Laue equivalent reflections. The structures were solved by direct methods using SIR92 2 and refined by full-matrix least squares on F 2 using the CRYSTALS suite 3 as per the details in the CIF.
This thesis describes the synthesis and reactivity of previously unprecedented bicyclic methylene... more This thesis describes the synthesis and reactivity of previously unprecedented bicyclic methylene aziridines via rhodium(II) catalysed cyclisation of α-allenic N-tosyloxycarbamates. These aziridines undergo reaction with organocuprates to give cis- disubstituted oxazolidinones by nucleophillic attack at the vinylic centre; plausible mechanisms for this process are discussed.Similar rhodium(II) catalysed cyclisations of β-allenic sulfamates afford cyclic enamines, aminocyclopropanes or bicyclic methylene aziridines; the product ratio depends on the allene substitution pattern. Suitably-designed substrates undergo trapping of the proposed intermediate amino allyl cation by internal nucleophiles or by cycloaddition.Finally, thermally-induced intramolecular cycloadditions of γ-allenic azides are described that give triazolines or [1,2,3]-triazoles.</p
An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol eth... more An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol ether spiroacetal isolated from Chrysanthemum boreale. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot-Chodkiewicz cross-coupling to install the bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward.
An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol et... more An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol ether spiroacetal isolated from <i>Chrysanthemum boreale</i>. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot–Chodkiewicz cross-coupling to install the bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
wR(F 2) = 0.093 S = 1.01 2321 reflections 118 parameters 4320 measured reflections 2321 independe... more wR(F 2) = 0.093 S = 1.01 2321 reflections 118 parameters 4320 measured reflections 2321 independent reflections 2094 reflections with I>2 (I) R int = 0.021 2 restraints H-atom parameters constrained max = 0.36 e A ˚ 3 min = 0.38 e A ˚ 3 Key indicators: single-crystal X-ray study; T = 150 K; mean (C–C) = 0.002 A˚; R factor = 0.035; wR factor = 0.093; data-to-parameter ratio = 19.7. X-ray crystallography was used to confirm the structure of the enantio-enriched title compound, C10H12Cl2O, a bicylic enol ether. A bridged boat-like structure is adopted and the dichloromethylene C atom is positioned significantly removed from the core bicyclic unit. In the crystal structure, molecules pack to form sheets approximately perpendicular to the a and c axes. Related literature
The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high... more The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using highthroughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200 g mL −1 .
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
A new method for the discovery of amphiphiles by using high-throughput (HT) methods to synthesise... more A new method for the discovery of amphiphiles by using high-throughput (HT) methods to synthesise and characterise a library of galactose-and glucose-containing amphiphilic compounds is presented. The copper-catalysed azide-alkyne cycloaddition (CuAAC) "click" reaction between azide-tethered simple sugars and alkyne-substituted hydrophobic tails was employed to synthesise a library of compounds with systematic variations in chain length and unsaturation in a 24-vial array format. The liquid-crystalline phase behaviour was characterised in a HT manner by using synchrotron small-angle X-ray scattering (SSAXS). The observed structural variation with respect to chain parameters, including chain length and degree of unsaturation, is discussed, as well as hydration effects and degree of hydrogen bonding between head groups. The validity of our HT screening approach was verified by resynthesising a shortchain glucose amphiphile. A separate phase analysis of this compound confirmed the presence of numerous lyotropic liquid-crystalline phases.
Beilstein Journal of Organic Chemistry, Jul 10, 2014
Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystal... more Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the coppercatalysed azide-alkyne cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.
Acta Crystallographica Section C-crystal Structure Communications, Nov 18, 2009
The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxid... more The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxide, C(9)H(15)NO(3)S, was found to crystallize with two molecules in the asymmetric unit. The structure was solved in both the approximately orthogonal and the oblique settings of space group No. 14, viz. P2(1)/n and P2(1)/c, respectively. A comparison of these results clearly displayed an increase in the correlation between coordinates in the ac plane for the oblique cell. The increase in the corresponding covariances makes a significant contribution to the standard uncertainties of derived parameters, e.g. bond lengths. Since there is yet no CIF definition for the full variance-covariance matrix, there are clear advantages to reporting the structure in the nonstandard space-group setting.
The Intramolecular Amination of Allenes.-Rhodium-bound nitrenoids are trapped by tethered allenes... more The Intramolecular Amination of Allenes.-Rhodium-bound nitrenoids are trapped by tethered allenes generating a variety of structures such as aminocyclopropanes (III) and methylene aziridines (IX). The aminocyclopropanes undergo substitution of the acetoxy group by a variety of nucleophiles, cf. formation of products (X) and (XII).-(FEAST, G. C.;
Colloids and Surfaces B: Biointerfaces, Mar 1, 2017
The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high... more The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using highthroughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200 g mL −1 .
Single crystal X-ray diffraction data were obtained using a Nonius Kappa-CCD area detector diffra... more Single crystal X-ray diffraction data were obtained using a Nonius Kappa-CCD area detector diffractometer, with graphite-monochromated Mo-K! radiation (! = 0.71073 Å) at 150 K. Cell parameters and intensity data were processed using the DENZO-SMN package 1 and reflection intensities were corrected for absorption effects by the multi-scan method, based on multiple scans of identical and Laue equivalent reflections. The structures were solved by direct methods using SIR92 2 and refined by full-matrix least squares on F 2 using the CRYSTALS suite 3 as per the details in the CIF.
This thesis describes the synthesis and reactivity of previously unprecedented bicyclic methylene... more This thesis describes the synthesis and reactivity of previously unprecedented bicyclic methylene aziridines via rhodium(II) catalysed cyclisation of α-allenic N-tosyloxycarbamates. These aziridines undergo reaction with organocuprates to give cis- disubstituted oxazolidinones by nucleophillic attack at the vinylic centre; plausible mechanisms for this process are discussed.Similar rhodium(II) catalysed cyclisations of β-allenic sulfamates afford cyclic enamines, aminocyclopropanes or bicyclic methylene aziridines; the product ratio depends on the allene substitution pattern. Suitably-designed substrates undergo trapping of the proposed intermediate amino allyl cation by internal nucleophiles or by cycloaddition.Finally, thermally-induced intramolecular cycloadditions of γ-allenic azides are described that give triazolines or [1,2,3]-triazoles.</p
An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol eth... more An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol ether spiroacetal isolated from Chrysanthemum boreale. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot-Chodkiewicz cross-coupling to install the bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward.
An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol et... more An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol ether spiroacetal isolated from <i>Chrysanthemum boreale</i>. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot–Chodkiewicz cross-coupling to install the bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
wR(F 2) = 0.093 S = 1.01 2321 reflections 118 parameters 4320 measured reflections 2321 independe... more wR(F 2) = 0.093 S = 1.01 2321 reflections 118 parameters 4320 measured reflections 2321 independent reflections 2094 reflections with I>2 (I) R int = 0.021 2 restraints H-atom parameters constrained max = 0.36 e A ˚ 3 min = 0.38 e A ˚ 3 Key indicators: single-crystal X-ray study; T = 150 K; mean (C–C) = 0.002 A˚; R factor = 0.035; wR factor = 0.093; data-to-parameter ratio = 19.7. X-ray crystallography was used to confirm the structure of the enantio-enriched title compound, C10H12Cl2O, a bicylic enol ether. A bridged boat-like structure is adopted and the dichloromethylene C atom is positioned significantly removed from the core bicyclic unit. In the crystal structure, molecules pack to form sheets approximately perpendicular to the a and c axes. Related literature
The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high... more The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using highthroughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200 g mL −1 .
Uploads
Papers by George Feast