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Papers by Antonin Tuynman

Nitric Oxide-biology and Chemistry, 2003

A series of isomeric methoxyindazoles has been evaluated as inhibitors of purified recombinant ne... more A series of isomeric methoxyindazoles has been evaluated as inhibitors of purified recombinant neuronal, inducible, and endothelial nitric oxide synthases (NOS). 7-Methoxyindazole (7-MI) was the most active compound of this series and displayed selectivity toward the constitutive neuronal (NOS I) and endothelial (NOS III) NOS isoforms, the inducible NOS II being almost insensitive to this inhibitor. 6-, 5-, and 4-Methoxyindazoles were almost inactive against all three NOS isoforms. Inhibition of NO and citrulline formation catalyzed by neuronal NOS in the presence of 7-MI appeared to be competitive versus both substrate L-arginine (L-arg) and (6R)-5,6,7,8-tetrahydrobiopterin (BH(4)) cofactor. 7-MI only slightly inhibited NADPH oxidase activity and was inactive against the cytochrome c (cyt c) reductase activity of neuronal NOS at concentrations up to 100-fold higher than its IC(50) value for inhibition of citrulline formation. UV/Vis and EPR studies indicated that 7-MI interacts with the oxygenase domain of neuronal NOS (NOS I(oxy)) in an identical manner but with a much lower affinity than 7-nitroindazole (7-NI). These results demonstrate that an indazole derivative bearing an electron-rich substituent in the 7-position is also a NOS I inhibitor and that such a compound presents strong similarities with the mechanism of inhibition of 7-NI.

Tetrahedron, 1996

ABSTRACT The syntheses of three bicyclic guanidines as model compounds for the guanidine alkaloid... more ABSTRACT The syntheses of three bicyclic guanidines as model compounds for the guanidine alkaloid ptilomycalin A are described. The guanidines are prepared from pyrrolidin-2-one via an N-acyliminium ion coupling reaction with silyl enol ethers and a direct guanylation with bis-Boc-thiourea and HgCl2 as the key steps.

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tetrahedron Letters, 1996

Studies Towards the Synthesis of Guanidine Alkaloids; Synthesis of a Tricyclic Guanidine from Suc... more Studies Towards the Synthesis of Guanidine Alkaloids; Synthesis of a Tricyclic Guanidine from Succinimide. -As part of a research towards the total synthesis of ptilomycalin A, the synthesis of the tricyclic guanidine (I) as a model compound is described. -(LOUWRIER, S.; OSTENDORF, M.; TUYNMAN, A.; HIEMSTRA, H.; Tetrahedron Lett. 37 (1996) 6, 905-908; Lab. Org. Chem., Amsterdam Inst. Mol. Stud., Univ. Amsterdam, NL-1018 WS Amsterdam, Neth.; EN)

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

European Journal of Biochemistry, 1998

Using both stopped-flow and conventional spectroscopy, the oxygenation of methyl phenyl sulphide ... more Using both stopped-flow and conventional spectroscopy, the oxygenation of methyl phenyl sulphide by both lactoperoxidase (LPO) and Coprinus cinereus peroxidase (CiP) was monitored. Controlled continuous addition of H 2 O 2 during turnover and monitoring the presence of native enzymes, compounds I, II and III, led to formation of the sulphoxide in high yield and enantioselectivity. Under those conditions, LPO catalysed the formation of (R) methyl phenyl sulphoxide with a yield of 85% and an enantiomeric excess (e.e.) of 80%. CiP catalysed the formation of (S) methyl phenyl sulphoxide with a yield of 84% and an e.e. of 73%. The enantioselective performance was markedly influenced by the purity of the enzymes used. Presence of compound III during turnover led to rapid inactivation of the peroxidases and, therefore, to both a lower yield of the sulphoxides and a lower enantioselectivity. Stopped-flow kinetic data show that, for both LPO and CiP, the transition of compound I to compound II depends on the concentration of the methyl phenyl sulphide, suggesting an oxygen-rebound mechanism. In line with this mechanism, a methyl phenyl sulphide radical cation was detected by EPR during turnover for LPO.

Journal of Biological Chemistry, 2000

Coprinus cinereus peroxidase (CiP) catalyze the enantioselective epoxidation of styrene and a num... more Coprinus cinereus peroxidase (CiP) catalyze the enantioselective epoxidation of styrene and a number of substituted derivatives with a reasonable enantiomeric excess (up to 80%) and in a moderate yield. Three major differences with respect to the chloroperoxidase from Caldariomyces fumago (CPO) are observed in the reactivity of MPO and CiP toward styrene derivatives. First, in contrast to CPO, MPO and CiP produced the (S)isomers of the epoxides in enantiomeric excess. Second, for MPO and CiP the H 2 O 2 had to be added very slowly (10 eq in 16 h) to prevent accumulation of catalytically inactive enzyme intermediates. Under these conditions, CPO hardly showed any epoxidizing activity; only with a high influx of H 2 O 2 (300 eq in 1.6 h) was epoxidation observed. Third, both MPO and CiP formed significant amounts of (substituted) benzaldehydes as side products as a consequence of C-␣-C-␤ bond cleavage of the styrene derivatives, whereas for CPO and cytochrome c peroxidase this activity is not observed. C-␣-C-␤ cleavage was the most prominent reaction catalyzed by CiP, whereas with MPO the relative amount of epoxide formed was higher. This is the first report of peroxidases catalyzing both epoxidation reactions and carboncarbon bond cleavage. The results are discussed in terms of mechanisms involving ferryl oxygen transfer and electron transfer, respectively.

Monatshefte Fur Chemie, 2000

Horseradish peroxidase (HRP), myeloperoxidase (MPO), and manganese peroxidase (MnP) have been sh... more Horseradish peroxidase (HRP), myeloperoxidase (MPO), and manganese peroxidase (MnP) have been shown to catalyze the asymmetric sulfoxidation of thioanisole. When H2O2 was added stepwise to MPO, a maximal yield of 78% was obtained at pH 5 (ee 23%), whereas an optimum in the enantiomeric excess (32%, (R)-sulfoxide) was found at pH 6 (60% yield). For MnP a yield of 18% and a high enantiomeric excess of 91% of the (S)-sulfoxide were obtained at pH 5 and a yield of 36% and an ee of 87% at pH 7.0. Optimization of the conversion catalyzed by horseradish peroxidase at pH 7.0 by controlled continuous addition of hydrogen peroxide during turnover and monitoring the presence of native enzyme as well as of intermediates I, II, and III led to the formation of the sulfoxide in high yield (100%) and moderate enantioselectivity (60%, (S)-sulfoxide).

Inorganic Chemistry, 1998

Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypoha... more Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypohalous acid. We demonstrate that these enzymes also slowly mediate the enantioselective oxidation of organic sulfides (methyl phenyl sulfide, methyl p-tolyl sulfide, and 1-methoxy-4 (methylthio)benzene) to the corresponding sulfoxides (turnover frequency 1 min(-)(1)). The vanadium bromoperoxidase from the brown seaweed Ascophyllum nodosum converts methyl phenyl sulfide to the (R)-enantiomer of the sulfoxide (55% yield and 85% enantiomeric excess (ee)). At low peroxide concentrations a selectivity of 91% can be attained. The enzyme catalyzes the selective sulfoxidation reaction over a broad pH range with an optimum around pH 5-6 and remains completely functional during the reaction. When the vanadium bromoperoxidase from the red seaweed Corallina pilulifera is used the (S)-enantiomer (18% yield and 55% ee) is formed. In contrast, the vanadium chloroperoxidase from the fungus Curvularia inaequalis catalyzes the production of a racemic mixture (54% yield), which seems to be an intrinsic characteristic of this enzyme.

Nitric Oxide-biology and Chemistry, 2003

A series of isomeric methoxyindazoles has been evaluated as inhibitors of purified recombinant ne... more A series of isomeric methoxyindazoles has been evaluated as inhibitors of purified recombinant neuronal, inducible, and endothelial nitric oxide synthases (NOS). 7-Methoxyindazole (7-MI) was the most active compound of this series and displayed selectivity toward the constitutive neuronal (NOS I) and endothelial (NOS III) NOS isoforms, the inducible NOS II being almost insensitive to this inhibitor. 6-, 5-, and 4-Methoxyindazoles were almost inactive against all three NOS isoforms. Inhibition of NO and citrulline formation catalyzed by neuronal NOS in the presence of 7-MI appeared to be competitive versus both substrate L-arginine (L-arg) and (6R)-5,6,7,8-tetrahydrobiopterin (BH(4)) cofactor. 7-MI only slightly inhibited NADPH oxidase activity and was inactive against the cytochrome c (cyt c) reductase activity of neuronal NOS at concentrations up to 100-fold higher than its IC(50) value for inhibition of citrulline formation. UV/Vis and EPR studies indicated that 7-MI interacts with the oxygenase domain of neuronal NOS (NOS I(oxy)) in an identical manner but with a much lower affinity than 7-nitroindazole (7-NI). These results demonstrate that an indazole derivative bearing an electron-rich substituent in the 7-position is also a NOS I inhibitor and that such a compound presents strong similarities with the mechanism of inhibition of 7-NI.

Tetrahedron, 1996

ABSTRACT The syntheses of three bicyclic guanidines as model compounds for the guanidine alkaloid... more ABSTRACT The syntheses of three bicyclic guanidines as model compounds for the guanidine alkaloid ptilomycalin A are described. The guanidines are prepared from pyrrolidin-2-one via an N-acyliminium ion coupling reaction with silyl enol ethers and a direct guanylation with bis-Boc-thiourea and HgCl2 as the key steps.

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tetrahedron Letters, 1996

Studies Towards the Synthesis of Guanidine Alkaloids; Synthesis of a Tricyclic Guanidine from Suc... more Studies Towards the Synthesis of Guanidine Alkaloids; Synthesis of a Tricyclic Guanidine from Succinimide. -As part of a research towards the total synthesis of ptilomycalin A, the synthesis of the tricyclic guanidine (I) as a model compound is described. -(LOUWRIER, S.; OSTENDORF, M.; TUYNMAN, A.; HIEMSTRA, H.; Tetrahedron Lett. 37 (1996) 6, 905-908; Lab. Org. Chem., Amsterdam Inst. Mol. Stud., Univ. Amsterdam, NL-1018 WS Amsterdam, Neth.; EN)

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

European Journal of Biochemistry, 1998

Using both stopped-flow and conventional spectroscopy, the oxygenation of methyl phenyl sulphide ... more Using both stopped-flow and conventional spectroscopy, the oxygenation of methyl phenyl sulphide by both lactoperoxidase (LPO) and Coprinus cinereus peroxidase (CiP) was monitored. Controlled continuous addition of H 2 O 2 during turnover and monitoring the presence of native enzymes, compounds I, II and III, led to formation of the sulphoxide in high yield and enantioselectivity. Under those conditions, LPO catalysed the formation of (R) methyl phenyl sulphoxide with a yield of 85% and an enantiomeric excess (e.e.) of 80%. CiP catalysed the formation of (S) methyl phenyl sulphoxide with a yield of 84% and an e.e. of 73%. The enantioselective performance was markedly influenced by the purity of the enzymes used. Presence of compound III during turnover led to rapid inactivation of the peroxidases and, therefore, to both a lower yield of the sulphoxides and a lower enantioselectivity. Stopped-flow kinetic data show that, for both LPO and CiP, the transition of compound I to compound II depends on the concentration of the methyl phenyl sulphide, suggesting an oxygen-rebound mechanism. In line with this mechanism, a methyl phenyl sulphide radical cation was detected by EPR during turnover for LPO.

Journal of Biological Chemistry, 2000

Coprinus cinereus peroxidase (CiP) catalyze the enantioselective epoxidation of styrene and a num... more Coprinus cinereus peroxidase (CiP) catalyze the enantioselective epoxidation of styrene and a number of substituted derivatives with a reasonable enantiomeric excess (up to 80%) and in a moderate yield. Three major differences with respect to the chloroperoxidase from Caldariomyces fumago (CPO) are observed in the reactivity of MPO and CiP toward styrene derivatives. First, in contrast to CPO, MPO and CiP produced the (S)isomers of the epoxides in enantiomeric excess. Second, for MPO and CiP the H 2 O 2 had to be added very slowly (10 eq in 16 h) to prevent accumulation of catalytically inactive enzyme intermediates. Under these conditions, CPO hardly showed any epoxidizing activity; only with a high influx of H 2 O 2 (300 eq in 1.6 h) was epoxidation observed. Third, both MPO and CiP formed significant amounts of (substituted) benzaldehydes as side products as a consequence of C-␣-C-␤ bond cleavage of the styrene derivatives, whereas for CPO and cytochrome c peroxidase this activity is not observed. C-␣-C-␤ cleavage was the most prominent reaction catalyzed by CiP, whereas with MPO the relative amount of epoxide formed was higher. This is the first report of peroxidases catalyzing both epoxidation reactions and carboncarbon bond cleavage. The results are discussed in terms of mechanisms involving ferryl oxygen transfer and electron transfer, respectively.

Monatshefte Fur Chemie, 2000

Horseradish peroxidase (HRP), myeloperoxidase (MPO), and manganese peroxidase (MnP) have been sh... more Horseradish peroxidase (HRP), myeloperoxidase (MPO), and manganese peroxidase (MnP) have been shown to catalyze the asymmetric sulfoxidation of thioanisole. When H2O2 was added stepwise to MPO, a maximal yield of 78% was obtained at pH 5 (ee 23%), whereas an optimum in the enantiomeric excess (32%, (R)-sulfoxide) was found at pH 6 (60% yield). For MnP a yield of 18% and a high enantiomeric excess of 91% of the (S)-sulfoxide were obtained at pH 5 and a yield of 36% and an ee of 87% at pH 7.0. Optimization of the conversion catalyzed by horseradish peroxidase at pH 7.0 by controlled continuous addition of hydrogen peroxide during turnover and monitoring the presence of native enzyme as well as of intermediates I, II, and III led to the formation of the sulfoxide in high yield (100%) and moderate enantioselectivity (60%, (S)-sulfoxide).

Inorganic Chemistry, 1998

Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypoha... more Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypohalous acid. We demonstrate that these enzymes also slowly mediate the enantioselective oxidation of organic sulfides (methyl phenyl sulfide, methyl p-tolyl sulfide, and 1-methoxy-4 (methylthio)benzene) to the corresponding sulfoxides (turnover frequency 1 min(-)(1)). The vanadium bromoperoxidase from the brown seaweed Ascophyllum nodosum converts methyl phenyl sulfide to the (R)-enantiomer of the sulfoxide (55% yield and 85% enantiomeric excess (ee)). At low peroxide concentrations a selectivity of 91% can be attained. The enzyme catalyzes the selective sulfoxidation reaction over a broad pH range with an optimum around pH 5-6 and remains completely functional during the reaction. When the vanadium bromoperoxidase from the red seaweed Corallina pilulifera is used the (S)-enantiomer (18% yield and 55% ee) is formed. In contrast, the vanadium chloroperoxidase from the fungus Curvularia inaequalis catalyzes the production of a racemic mixture (54% yield), which seems to be an intrinsic characteristic of this enzyme.