Carla Marchioro - Academia.edu (original) (raw)
Papers by Carla Marchioro
Journal of Organic Chemistry, Sep 19, 2002
To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA ... more To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding alpha amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.
Tetrahedron-asymmetry, Mar 1, 1997
The title compound was obtained with high regioisomeric and enantiomeric
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Journal of combinatorial chemistry, Oct 2, 2003
Different arene Cr(CO)(3) complexes were supported on a polystyrene isonitrile resin by photochem... more Different arene Cr(CO)(3) complexes were supported on a polystyrene isonitrile resin by photochemical-promoted replacement of a chromium carbonyl ligand by the NC group. The supported complexes proved to be stable and were successfully used for further transformations. In particular, the reactivity of dichlorobenzene complexes to different nucleophiles was investigated and found to be comparable with that of the parent Cr(CO)(3) complexes.
Farmaco, Sep 1, 2003
A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was desi... more A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was designed and evaluated by superimposition with the pharmacophore model of the glycine binding site. To fully explore the SAR of this class of compounds and to allow the preparation of new different compounds at the C-3 position, appropriate synthetic routes were set up. The benzoazepines were evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. This further analysis confirmed the preliminary results previously reported and that compound 27 is the most promising compound (Ki=32 nM, ED(50)=0.09 mg/kg, i.v.) in this series. Significant neuroprotective effect was observed after both pre- and post-ischaemia administration in the MCAo model. In particular, after post-ischaemia administration, it was found to be still effective when the administration was delayed up to 6 h after occlusion of the middle cerebral artery.
Organic preparations and procedures international, Feb 1, 1992
... WITH SODIUM BOROHYDRIDE Submitted by (W/08/9 1) Daniele Donati', Carla Marchioro, Bruno ... more ... WITH SODIUM BOROHYDRIDE Submitted by (W/08/9 1) Daniele Donati', Carla Marchioro, Bruno Tamburini and Antonella Ursini Glaxo Research Laboratories, Via A. Fleming 2,37100 Verona, ITALY ... COOH 1 COOR 3 COOR 2 py-P 0 I 4 COOR COOR 3 OH 4 \ COOR ...
Bioorganic & Medicinal Chemistry Letters, Sep 1, 2011
Magnetic Resonance in Chemistry, 2001
The gradient‐enhanced 1H,29Si HMQC experiment was applied to tetra‐TMS‐α‐O‐methyl‐D‐glucopyranose... more The gradient‐enhanced 1H,29Si HMQC experiment was applied to tetra‐TMS‐α‐O‐methyl‐D‐glucopyranose and tetra‐TES‐α‐O‐methyl‐D‐glucopyranose as test samples. All the expected 2J(1H, 29Si) and 3J (1H,29Si) cross peaks were observed, allowing the full 29Si NMR assignment. An analysis of the trend of 29Si chemical shifts depending on the position of the silylating group in the sugar ring and on the different hindrances of TMS and TES groups is also reported. Copyright © 2001 John Wiley & Sons, Ltd.
Journal of the Chemical Society, 1997
... Carla Marchioro,* Giorgio Pentassuglia,* Alcide Perboni and Daniele Donati ... Gaviraghi, A. ... more ... Carla Marchioro,* Giorgio Pentassuglia,* Alcide Perboni and Daniele Donati ... Gaviraghi, A. Perboni, A. Pezzoli, T. Rossi, B. Tamburini and A. Ursini, J. Antibiot., 1995, 48, 399; (d) TN Salzmann, FP DiNinno, ML Greenlee, RN Guthikonda, ML Quesada, SM Schmitt, JJ Herrmann ...
Farmaco, Jul 1, 1999
The asymmetric synthesis of carboxyphenyl prolines was performed according to Schöllkopf methodol... more The asymmetric synthesis of carboxyphenyl prolines was performed according to Schöllkopf methodology, to prepare possible antagonists of the metabotropic glutamate receptor mGluR1.
ChemInform, Aug 4, 2010
5-and 7-Oxa Trinems: Their Synthesis and Biological Evaluation.-Novel oxa derivatives of trinems ... more 5-and 7-Oxa Trinems: Their Synthesis and Biological Evaluation.-Novel oxa derivatives of trinems are synthesized and tested for their antimicrobial activity. Preliminary results support the idea that introduction of the oxygen can exert a positive influence on the biological profile. Among the derivatives prepared, compounds (VI) and (XII) are the most active compounds.-(ANDREOTTI, D.;
ChemInform, Jun 12, 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.
Journal of Heterocyclic Chemistry, Jul 1, 1994
ABSTRACT The synthesis of a series of 6,6-disubstituted penems starting from penicillanate 5a is ... more ABSTRACT The synthesis of a series of 6,6-disubstituted penems starting from penicillanate 5a is described. These penems were isolated and characterized as their pivaloyloxy methyl ester.
Journal of combinatorial chemistry, Jun 11, 1999
This paper describes the successful transfer of benzotriazole-based chemistry on solid support. T... more This paper describes the successful transfer of benzotriazole-based chemistry on solid support. The strategy followed to anchor this peculiar heterocycle on solid phase and the full analytical characterization of the various supported benzotriazoles are herein described. The chemistry assessment process on solid phase, the preparation of discrete libraries by parallel synthesis, the semiautomated purification procedures, and the complete analytical characterization of the library components are also presented and discussed.
Journal of Organic Chemistry, Mar 1, 1997
ABSTRACT (2S)-2-Methoxycyclohexanone [(2S)-6], reacts with the 4-acetoxyazetidinone 3a in the pre... more ABSTRACT (2S)-2-Methoxycyclohexanone [(2S)-6], reacts with the 4-acetoxyazetidinone 3a in the presence of SnCl4 and a tertiary amine base (such as N,N-diisopropylethylamine) to give the ketoazetidinone 5 (a key intermediate in the synthesis of the broad-spectrum antibiotic sanfetrinem 2a) with high yield and diastereoselectivity. Low-temperature NMR studies of the reaction indicated the formation of a 1:1 chelate complex 11 between SnCl4 and (2S)-6 which, on addition of the base is transformed into the highly reactive chelated tin enolate 12. The formation of compound 11 has been confirmed by single-crystal X-ray analysis. The high diastereoselectivity observed is believed to derive from an open transition state where the chelated SnCl4 amplifies the stereochemical influence of the methoxy group. This reaction offers considerable advantages over all existing syntheses of the ketoazetidinone 5 and is currently under evaluation for inclusion in the industrial synthesis of sanfetrinem.
Tetrahedron-asymmetry, Aug 1, 1998
The unexpected (3S,4R)-3-[(R)-1-(hydroxy)ethyl]-4-[(2 R,6 S)-1-oxo-2-(N-benzyloxy-N-methyl)aminoc... more The unexpected (3S,4R)-3-[(R)-1-(hydroxy)ethyl]-4-[(2 R,6 S)-1-oxo-2-(N-benzyloxy-N-methyl)aminocyclohexen-6-yl]-1-(t-butyl-dimethylsilyl)azetidin-2-one was one of the main reaction products of the Lewis acid catalysed condensation of (3S,4R)-3-[(R)-1-(t-butyl-dimethylsilyloxy)ethyl]-4-acetoxyazetidin-2-one with 1-trimethylsilyloxy-6-(N-benzyloxycarbonyl-N-methylamino)cyclohexene. Its absolute configuration was established by NMR experiments on the corresponding, conformationally rigid, acetonide derivative.
Journal of Pharmaceutical and Biomedical Analysis, Nov 1, 2010
Vestipitant (1) is a novel NK1 antagonist currently under investigation for the treatment of CNS ... more Vestipitant (1) is a novel NK1 antagonist currently under investigation for the treatment of CNS disorders and emesis. The first synthetic step comprised a Grignard synthesis. An impurity was identified and initially expected to be a symmetric biphenyl. This paper reports the work to synthesise the supposed structure and the spectroscopic analyses (LC-NMR and HR-NMR) to correctly identify the real structure and understand the chemical pathway of the impurity.
Bioorganic & Medicinal Chemistry, Jul 1, 2011
ABSTRACT This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureid... more ABSTRACT This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 was replaced with more hydrophilic substituents, like alkyl groups bearing basic functions. In some cases, the resolution of the racemic key intermediates 3-amino-benzodiazepines was also accomplished. Among the compounds synthesized and characterised so far in this class, the 5-morpholinoethyl derivative 54, was selected as potential follow up of GV150013 and submitted for further evaluation.
Journal of Organic Chemistry, Sep 19, 2002
To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA ... more To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding alpha amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.
Tetrahedron-asymmetry, Mar 1, 1997
The title compound was obtained with high regioisomeric and enantiomeric
Journal of combinatorial chemistry, Oct 2, 2003
Different arene Cr(CO)(3) complexes were supported on a polystyrene isonitrile resin by photochem... more Different arene Cr(CO)(3) complexes were supported on a polystyrene isonitrile resin by photochemical-promoted replacement of a chromium carbonyl ligand by the NC group. The supported complexes proved to be stable and were successfully used for further transformations. In particular, the reactivity of dichlorobenzene complexes to different nucleophiles was investigated and found to be comparable with that of the parent Cr(CO)(3) complexes.
Farmaco, Sep 1, 2003
A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was desi... more A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was designed and evaluated by superimposition with the pharmacophore model of the glycine binding site. To fully explore the SAR of this class of compounds and to allow the preparation of new different compounds at the C-3 position, appropriate synthetic routes were set up. The benzoazepines were evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. This further analysis confirmed the preliminary results previously reported and that compound 27 is the most promising compound (Ki=32 nM, ED(50)=0.09 mg/kg, i.v.) in this series. Significant neuroprotective effect was observed after both pre- and post-ischaemia administration in the MCAo model. In particular, after post-ischaemia administration, it was found to be still effective when the administration was delayed up to 6 h after occlusion of the middle cerebral artery.
Organic preparations and procedures international, Feb 1, 1992
... WITH SODIUM BOROHYDRIDE Submitted by (W/08/9 1) Daniele Donati', Carla Marchioro, Bruno ... more ... WITH SODIUM BOROHYDRIDE Submitted by (W/08/9 1) Daniele Donati', Carla Marchioro, Bruno Tamburini and Antonella Ursini Glaxo Research Laboratories, Via A. Fleming 2,37100 Verona, ITALY ... COOH 1 COOR 3 COOR 2 py-P 0 I 4 COOR COOR 3 OH 4 \ COOR ...
Bioorganic & Medicinal Chemistry Letters, Sep 1, 2011
Magnetic Resonance in Chemistry, 2001
The gradient‐enhanced 1H,29Si HMQC experiment was applied to tetra‐TMS‐α‐O‐methyl‐D‐glucopyranose... more The gradient‐enhanced 1H,29Si HMQC experiment was applied to tetra‐TMS‐α‐O‐methyl‐D‐glucopyranose and tetra‐TES‐α‐O‐methyl‐D‐glucopyranose as test samples. All the expected 2J(1H, 29Si) and 3J (1H,29Si) cross peaks were observed, allowing the full 29Si NMR assignment. An analysis of the trend of 29Si chemical shifts depending on the position of the silylating group in the sugar ring and on the different hindrances of TMS and TES groups is also reported. Copyright © 2001 John Wiley & Sons, Ltd.
Journal of the Chemical Society, 1997
... Carla Marchioro,* Giorgio Pentassuglia,* Alcide Perboni and Daniele Donati ... Gaviraghi, A. ... more ... Carla Marchioro,* Giorgio Pentassuglia,* Alcide Perboni and Daniele Donati ... Gaviraghi, A. Perboni, A. Pezzoli, T. Rossi, B. Tamburini and A. Ursini, J. Antibiot., 1995, 48, 399; (d) TN Salzmann, FP DiNinno, ML Greenlee, RN Guthikonda, ML Quesada, SM Schmitt, JJ Herrmann ...
Farmaco, Jul 1, 1999
The asymmetric synthesis of carboxyphenyl prolines was performed according to Schöllkopf methodol... more The asymmetric synthesis of carboxyphenyl prolines was performed according to Schöllkopf methodology, to prepare possible antagonists of the metabotropic glutamate receptor mGluR1.
ChemInform, Aug 4, 2010
5-and 7-Oxa Trinems: Their Synthesis and Biological Evaluation.-Novel oxa derivatives of trinems ... more 5-and 7-Oxa Trinems: Their Synthesis and Biological Evaluation.-Novel oxa derivatives of trinems are synthesized and tested for their antimicrobial activity. Preliminary results support the idea that introduction of the oxygen can exert a positive influence on the biological profile. Among the derivatives prepared, compounds (VI) and (XII) are the most active compounds.-(ANDREOTTI, D.;
ChemInform, Jun 12, 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.
Journal of Heterocyclic Chemistry, Jul 1, 1994
ABSTRACT The synthesis of a series of 6,6-disubstituted penems starting from penicillanate 5a is ... more ABSTRACT The synthesis of a series of 6,6-disubstituted penems starting from penicillanate 5a is described. These penems were isolated and characterized as their pivaloyloxy methyl ester.
Journal of combinatorial chemistry, Jun 11, 1999
This paper describes the successful transfer of benzotriazole-based chemistry on solid support. T... more This paper describes the successful transfer of benzotriazole-based chemistry on solid support. The strategy followed to anchor this peculiar heterocycle on solid phase and the full analytical characterization of the various supported benzotriazoles are herein described. The chemistry assessment process on solid phase, the preparation of discrete libraries by parallel synthesis, the semiautomated purification procedures, and the complete analytical characterization of the library components are also presented and discussed.
Journal of Organic Chemistry, Mar 1, 1997
ABSTRACT (2S)-2-Methoxycyclohexanone [(2S)-6], reacts with the 4-acetoxyazetidinone 3a in the pre... more ABSTRACT (2S)-2-Methoxycyclohexanone [(2S)-6], reacts with the 4-acetoxyazetidinone 3a in the presence of SnCl4 and a tertiary amine base (such as N,N-diisopropylethylamine) to give the ketoazetidinone 5 (a key intermediate in the synthesis of the broad-spectrum antibiotic sanfetrinem 2a) with high yield and diastereoselectivity. Low-temperature NMR studies of the reaction indicated the formation of a 1:1 chelate complex 11 between SnCl4 and (2S)-6 which, on addition of the base is transformed into the highly reactive chelated tin enolate 12. The formation of compound 11 has been confirmed by single-crystal X-ray analysis. The high diastereoselectivity observed is believed to derive from an open transition state where the chelated SnCl4 amplifies the stereochemical influence of the methoxy group. This reaction offers considerable advantages over all existing syntheses of the ketoazetidinone 5 and is currently under evaluation for inclusion in the industrial synthesis of sanfetrinem.
Tetrahedron-asymmetry, Aug 1, 1998
The unexpected (3S,4R)-3-[(R)-1-(hydroxy)ethyl]-4-[(2 R,6 S)-1-oxo-2-(N-benzyloxy-N-methyl)aminoc... more The unexpected (3S,4R)-3-[(R)-1-(hydroxy)ethyl]-4-[(2 R,6 S)-1-oxo-2-(N-benzyloxy-N-methyl)aminocyclohexen-6-yl]-1-(t-butyl-dimethylsilyl)azetidin-2-one was one of the main reaction products of the Lewis acid catalysed condensation of (3S,4R)-3-[(R)-1-(t-butyl-dimethylsilyloxy)ethyl]-4-acetoxyazetidin-2-one with 1-trimethylsilyloxy-6-(N-benzyloxycarbonyl-N-methylamino)cyclohexene. Its absolute configuration was established by NMR experiments on the corresponding, conformationally rigid, acetonide derivative.
Journal of Pharmaceutical and Biomedical Analysis, Nov 1, 2010
Vestipitant (1) is a novel NK1 antagonist currently under investigation for the treatment of CNS ... more Vestipitant (1) is a novel NK1 antagonist currently under investigation for the treatment of CNS disorders and emesis. The first synthetic step comprised a Grignard synthesis. An impurity was identified and initially expected to be a symmetric biphenyl. This paper reports the work to synthesise the supposed structure and the spectroscopic analyses (LC-NMR and HR-NMR) to correctly identify the real structure and understand the chemical pathway of the impurity.
Bioorganic & Medicinal Chemistry, Jul 1, 2011
ABSTRACT This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureid... more ABSTRACT This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 was replaced with more hydrophilic substituents, like alkyl groups bearing basic functions. In some cases, the resolution of the racemic key intermediates 3-amino-benzodiazepines was also accomplished. Among the compounds synthesized and characterised so far in this class, the 5-morpholinoethyl derivative 54, was selected as potential follow up of GV150013 and submitted for further evaluation.