The Experts below are selected from a list of 440769 Experts worldwide ranked by ideXlab platform
Stephen G. Pyne - One of the best experts on this subject based on the ideXlab platform.
-
Asymmetric synthesis of (-)-swainsonine, (+)-1,2-di-epi-swainsonine, and (+)-1,2,8-tri-epi-swainsonine.
Journal of Organic Chemistry, 2002Co-Authors: Karl B. Lindsay, Stephen G. PyneAbstract:The asymmetric synthesis of (−)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective Cis-Dihydroxylation using AD-mix-α. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.
-
asymmetric synthesis of swainsonine 1 2 di epi swainsonine and 1 2 8 tri epi swainsonine
Journal of Organic Chemistry, 2002Co-Authors: Karl B. Lindsay, Stephen G. PyneAbstract:The asymmetric synthesis of (−)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective Cis-Dihydroxylation using AD-mix-α. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.
Christopher C. R. Allen - One of the best experts on this subject based on the ideXlab platform.
-
biphenyl dioxygenase catalysed cis dihydroxylation of tricyclic azaarenes chemoenzymatic synthesis of arene oxide metabolites and furoquinoline alkaloids
RSC Advances, 2013Co-Authors: Derek R. Boyd, Jonathan G Carroll, Pui L Loke, Colin Odowd, Narain D. Sharma, Christopher C. R. AllenAbstract:Biotransformation of acridine, dictamnine and 4-chlorofuro[2,3-b]quinolone, using whole cells of Sphingomonas yanoikuyae B8/36, yielded five enantiopure cyclic cis-dihydrodiols, from biphenyl dioxygenase-catalysed dihydroxylation of the carbocyclic rings. Cis-Dihydroxylation of the furan ring in dictamnine and 4-chlorofuro[2,3-b]quinoline, followed by ring opening and reduction, yielded two exocyclic diols. The structures and absolute configurations of metabolites have been determined by spectroscopy and stereochemical correlation methods. Enantiopure arene oxide metabolites of acridine and dictamnine have been synthesised, from the corresponding cis-dihydrodiols. The achiral furoquinoline alkaloids robustine, γ-fagarine, haplopine, isohaplopine-3,3′-dimethylallylether and pteleine have been obtained, from either cis-dihydrodiol, catechol or arene oxide metabolites of dictamnine.
-
Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from substituted benzene substrates.
Organic and Biomolecular Chemistry, 2013Co-Authors: Derek R. Boyd, Vera Ljubez, Peter K. M. Mcgeehin, Marine Blain, Paul J. Stevenson, Narain D. Sharma, Christopher C. R. AllenAbstract:Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Arene hydrates have also been synthesised, in enantiopure form, from the corresponding dihydroarene oxide or trans-bromoacetate precursors. Biotransformation of one arene hydrate enantiomer resulted in a toluene-dioxygenase catalysed Cis-Dihydroxylation to yield a benzene cis-triol metabolite.
-
dioxygenase catalysed cis dihydroxylation of meta substituted phenols to yield cyclohexenone cis diol and derived enantiopure cis triol metabolites
Organic and Biomolecular Chemistry, 2011Co-Authors: Derek R. Boyd, Marine Blain, Paul J. Stevenson, Narain D. Sharma, John T. G Hamilton, Colin Mcroberts, Jose M Argudo, Harpinder Mundi, Leonid Kulakov, Christopher C. R. AllenAbstract:Cis-Dihydroxylation of meta-substituted phenol (m-phenol) substrates, to yield the corresponding cyclohexenonecis-diol metabolites, was catalysed by arene dioxygenases present in mutant and recombinant bacterial strains. The presence of cyclohexenonecis-diol metabolites and several of their cyclohexene and cyclohexane cis-triol derivatives was detected by LC-TOFMS analysis and confirmed by NMR spectroscopy. Structural and stereochemical analyses of chiral ketodiol bioproducts, was carried out using NMR and CD spectroscopy and stereochemical correlation methods. The formation of enantiopure cyclohexenonecis-diol metabolites is discussed in the context of postulated binding interactions of the m-phenol substrates at the active site of toluene dioxygenase (TDO).
-
new families of enantiopure cyclohexenone cis diol o quinol dimer and hydrate metabolites from dioxygenase catalysed dihydroxylation of phenols
Chemical Communications, 2009Co-Authors: Derek R. Boyd, John F. Malone, Narain D. Sharma, Christopher C. R. AllenAbstract:Toluene dioxygenase-catalysed Cis-Dihydroxylation of phenols has led to the discovery of new enantiopure cyclohexenonecis-diol, o-quinol dimer and phenol hydrate metabolites having synthetic potential.
-
cis dihydrodiol arene oxide and phenol metabolites of dictamnine key intermediates in the biodegradation and biosynthesis of furoquinoline alkaloids
Chemical Communications, 2005Co-Authors: Derek R. Boyd, Jonathan G Carroll, Pui L Loke, Colin Odowd, Narain D. Sharma, Christopher C. R. AllenAbstract:Biotransformation of the parent furoquinoline alkaloid dictamnine and its 4-chlorofuroquinoline precursor, using the B8/36 bacterial mutant strain of Sphingomonas yanoikuyae, yielded, via biphenyl dioxygenase-catalysed dihydroxylation, the first isolable alkaloid cis-dihydrodiol metabolites; these metabolites were used in the chemoenzymatic synthesis of postulated arene oxide and phenol intermediates, and a range of derived furoquinoline alkaloids.
Derek R. Boyd - One of the best experts on this subject based on the ideXlab platform.
-
biphenyl dioxygenase catalysed cis dihydroxylation of tricyclic azaarenes chemoenzymatic synthesis of arene oxide metabolites and furoquinoline alkaloids
RSC Advances, 2013Co-Authors: Derek R. Boyd, Jonathan G Carroll, Pui L Loke, Colin Odowd, Narain D. Sharma, Christopher C. R. AllenAbstract:Biotransformation of acridine, dictamnine and 4-chlorofuro[2,3-b]quinolone, using whole cells of Sphingomonas yanoikuyae B8/36, yielded five enantiopure cyclic cis-dihydrodiols, from biphenyl dioxygenase-catalysed dihydroxylation of the carbocyclic rings. Cis-Dihydroxylation of the furan ring in dictamnine and 4-chlorofuro[2,3-b]quinoline, followed by ring opening and reduction, yielded two exocyclic diols. The structures and absolute configurations of metabolites have been determined by spectroscopy and stereochemical correlation methods. Enantiopure arene oxide metabolites of acridine and dictamnine have been synthesised, from the corresponding cis-dihydrodiols. The achiral furoquinoline alkaloids robustine, γ-fagarine, haplopine, isohaplopine-3,3′-dimethylallylether and pteleine have been obtained, from either cis-dihydrodiol, catechol or arene oxide metabolites of dictamnine.
-
Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from substituted benzene substrates.
Organic and Biomolecular Chemistry, 2013Co-Authors: Derek R. Boyd, Vera Ljubez, Peter K. M. Mcgeehin, Marine Blain, Paul J. Stevenson, Narain D. Sharma, Christopher C. R. AllenAbstract:Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Arene hydrates have also been synthesised, in enantiopure form, from the corresponding dihydroarene oxide or trans-bromoacetate precursors. Biotransformation of one arene hydrate enantiomer resulted in a toluene-dioxygenase catalysed Cis-Dihydroxylation to yield a benzene cis-triol metabolite.
-
dioxygenase catalysed cis dihydroxylation of meta substituted phenols to yield cyclohexenone cis diol and derived enantiopure cis triol metabolites
Organic and Biomolecular Chemistry, 2011Co-Authors: Derek R. Boyd, Marine Blain, Paul J. Stevenson, Narain D. Sharma, John T. G Hamilton, Colin Mcroberts, Jose M Argudo, Harpinder Mundi, Leonid Kulakov, Christopher C. R. AllenAbstract:Cis-Dihydroxylation of meta-substituted phenol (m-phenol) substrates, to yield the corresponding cyclohexenonecis-diol metabolites, was catalysed by arene dioxygenases present in mutant and recombinant bacterial strains. The presence of cyclohexenonecis-diol metabolites and several of their cyclohexene and cyclohexane cis-triol derivatives was detected by LC-TOFMS analysis and confirmed by NMR spectroscopy. Structural and stereochemical analyses of chiral ketodiol bioproducts, was carried out using NMR and CD spectroscopy and stereochemical correlation methods. The formation of enantiopure cyclohexenonecis-diol metabolites is discussed in the context of postulated binding interactions of the m-phenol substrates at the active site of toluene dioxygenase (TDO).
-
new families of enantiopure cyclohexenone cis diol o quinol dimer and hydrate metabolites from dioxygenase catalysed dihydroxylation of phenols
Chemical Communications, 2009Co-Authors: Derek R. Boyd, John F. Malone, Narain D. Sharma, Christopher C. R. AllenAbstract:Toluene dioxygenase-catalysed Cis-Dihydroxylation of phenols has led to the discovery of new enantiopure cyclohexenonecis-diol, o-quinol dimer and phenol hydrate metabolites having synthetic potential.
-
Dioxygenase-catalysed oxidation of disubstituted benzene substrates : benzylic monohydroxylation versus aryl Cis-Dihydroxylation and the meta effect
Organic & biomolecular chemistry, 2006Co-Authors: Derek R. Boyd, Narain D. Sharma, Nigel I. Bowers, Howard Dalton, John S. Harrison, Mark D. Garrett, Gary N. SheldrakeAbstract:Biotransformations of a series of ortho-, meta- and para-substituted ethylbenzene and propylbenzene substrates have been carried out, using Pseudomonas putida UV4, a source of toluene dioxygenase (TDO). The ortho- and para-substituted alkylbenzene substrates yielded, exclusively, the corresponding enantiopure cis-dihydrodiols of the same absolute configuration. However, the meta isomers, generally, gave benzylic alcohol bioproducts, in addition to the cis-dihydrodiols (the meta effect). The benzylic alcohols were of identical (R) absolute configuration but enantiomeric excess values were variable. The similar (2R) absolute configurations of the cis-dihydrodiols are consistent with both the ethyl and propyl groups having dominant stereodirecting effects over the other substituents. The model used earlier, to predict the regio- and stereo-chemistry of cis-dihydrodiol bioproducts derived from substituted benzene substrates has been refined, to take account of non-symmetric subsituents like ethyl or propyl groups. The formation of benzylic hydroxylation products, from meta-substituted benzene substrates, without further Cis-Dihydroxylation to yield triols provides a further example of the meta effect during toluene dioxygenase-catalysed oxidations.
Karl B. Lindsay - One of the best experts on this subject based on the ideXlab platform.
-
Asymmetric synthesis of (-)-swainsonine, (+)-1,2-di-epi-swainsonine, and (+)-1,2,8-tri-epi-swainsonine.
Journal of Organic Chemistry, 2002Co-Authors: Karl B. Lindsay, Stephen G. PyneAbstract:The asymmetric synthesis of (−)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective Cis-Dihydroxylation using AD-mix-α. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.
-
asymmetric synthesis of swainsonine 1 2 di epi swainsonine and 1 2 8 tri epi swainsonine
Journal of Organic Chemistry, 2002Co-Authors: Karl B. Lindsay, Stephen G. PyneAbstract:The asymmetric synthesis of (−)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective Cis-Dihydroxylation using AD-mix-α. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.
David T Gibson - One of the best experts on this subject based on the ideXlab platform.
-
Regio- and stereo-selective dioxygenase-catalysed Cis-Dihydroxylation of fjord-region polycyclic arenes
Journal of The Chemical Society-perkin Transactions 1, 2001Co-Authors: Derek R. Boyd, Martina A. Kennedy, Narain D. Sharma, Christopher C. R. Allen, John S. Harrison, David T GibsonAbstract:Bacterial dioxygenase-catalysed Cis-Dihydroxylation of the tetracyclic arenes benzo[c]phenanthrene 2, and the isosteric compounds benzo[b]naphtho[1,2-d]furan 8, and benzo[b]naphtho[1,2-d]thiophene 9, has been found to occur exclusively at fjord-region bonds. The resulting cis-dihydrodiols 7, 10 and 11 were found to be enantiopure and of similar absolute configuration. Cis-Dihydroxylation was also observed in the pseudo-fjord region of the 8,9,10,11-tetrahydro-precursors (12 and 13) of benzo[b]naphtho[1,2-d]furan 8, and benzo[b]naphtho[1,2-d]thiophene 9, to yield the corresponding enantiopure hexahydro cis-diols 14 and 15. A novel tandem Cis-Dihydroxylation and bis-desaturation of the tetrahydro-substrate, tetrahydrobenzo[b]naphtho[1,2-d]thiophene 13, catalysed by biphenyl dioxygenase, was found to yield the fjord-region cis-dihydrodiol 17 of benzo[b]naphtho[1,2-d]thiophene 9.
-
substrate specificity of naphthalene dioxygenase effect of specific amino acids at the active site of the enzyme
Journal of Bacteriology, 2000Co-Authors: Rebecca E Parales, Sol M Resnick, Haiyan Jiang, Daniel J Lessner, David T GibsonAbstract:The three-component naphthalene dioxygenase (NDO) enzyme system carries out the first step in the aerobic degradation of naphthalene by Pseudomonas sp. strain NCIB 9816-4. The three-dimensional structure of NDO revealed that several of the amino acids at the active site of the oxygenase are hydrophobic, which is consistent with the enzyme's preference for aromatic hydrocarbon substrates. Although NDO catalyzes Cis-Dihydroxylation of a wide range of substrates, it is highly regio- and enantioselective. Site-directed mutagenesis was used to determine the contributions of several active-site residues to these aspects of catalysis. Amino acid substitutions at Asn-201, Phe-202, Val-260, Trp-316, Thr-351, Trp-358, and Met-366 had little or no effect on product formation with naphthalene or biphenyl as substrates and had slight but significant effects on product formation from phenanthrene. Amino acid substitutions at Phe-352 resulted in the formation of cis-naphthalene dihydrodiol with altered stereochemistry [92 to 96% (+)-1R,2S], compared to the enantiomerically pure [>99% (+)-1R,2S] product formed by the wild-type enzyme. Substitutions at position 352 changed the site of oxidation of biphenyl and phenanthrene. Substitution of alanine for Asp-362, a ligand to the active-site iron, resulted in a completely inactive enzyme.
-
bis-cis-dihydrodiols: A new class of metabolites resulting from biphenyl dioxygenase-catalyzed sequential asymmetric Cis-Dihydroxylation of polycyclic arenes and heteroarenes
Journal of Organic Chemistry, 1999Co-Authors: Derek R. Boyd, Francis Hempenstall, Martina A. Kennedy, John F. Malone, Narain D. Sharma, Christopher C. R. Allen, Sol M Resnick, David T GibsonAbstract:The biphenyl dioxygenase-catalyzed asymmetric mono-Cis-Dihydroxylation of the tetracyclic arenes chrysene 1A, benzo[c]phenanthridine 1B, and benzo[b]naphtho[2,1-d]thiophene 1C, has been observed to occur exclusively at the bay or pseudo-bay region using the bacterium Sphingomonas yanoikuyae B8/36. The mono-cis-dihydrodiol derivatives 2A and 2C, obtained from chrysene 1A by oxidation at the 3,4-bond (2A) and benzo[b]naphtho[2,1-d]thiophene 1C by oxidation at the 1,2-bond (2C), respectively, have been observed to undergo a further dioxygenase-catalyzed asymmetric Cis-Dihydroxylation at a second bay or pseudo-bay region bond to yield the corresponding bis-cis-dihydrodiols (cis-tetraols) 4A and 4C, the first members of a new class of microbial metabolites in the polycyclic arene series. The enantiopurities and absolute configurations of the new mono-cis-dihydrodiols 2B, 2C, and 3B were determined by 1H NMR analyses of the corresponding (R)- and (S)-2-(1-methoxyethyl)benzeneboronate (MPBA) ester derivatives. T...
-
desaturation and oxygenation of 1 2 dihydronaphthalene by toluene and naphthalene dioxygenase
Journal of Bacteriology, 1995Co-Authors: D S Torok, J M Brand, Diana L Cruden, Sol M Resnick, David T GibsonAbstract:Bacterial strains expressing toluene and naphthalene dioxygenase were used to examine the sequence of reactions involved in the oxidation of 1,2-dihydronaphthalene. Toluene dioxygenase of Pseudomonas putida F39/D oxidizes 1,2-dihydronaphthalene to (+)-cis-(1S,2R)-dihydroxy-1,2,3,4-tetrahydronaphthalene, (+)-(1R)-hydroxy-1,2-dihydronaphthalene, and (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. In contrast, naphthalene dioxygenase of Pseudomonas sp. strain NCIB 9816/11 oxidizes 1,2-dihydronaphthalene to the opposite enantiomer, (-)-cis-(1R,2S)-dihydroxy-1,2,3,4-tetrahydronaphthalene and the identical (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. Recombinant Escherichia coli strains expressing the structural genes for toluene and naphthalene dioxygenases confirmed the involvement of these enzymes in the reactions catalyzed by strains F39/D and NCIB 9816/11. 1-Hydroxy-1,2-dihydronaphthalene was not formed by strains expressing naphthalene dioxygenase. These results coupled with time course studies and deuterium labelling experiments indicate that, in addition to direct dioxygenation of the olefin, both enzymes have the ability to desaturate (dehydrogenate) 1,2-dihydronaphthalene to naphthalene, which serves as a substrate for cis dihydroxylation.