TY  - JOUR
AU  - Ferjancic, Zorana
AU  - Bihelovic, Filip
AU  - Vulovic, Bojan
AU  - Matovic, Radomir
AU  - Trmcic, Milena
AU  - Jankovic, Aleksandar
AU  - Pavlovic, Milos
AU  - Djurkovic, Filip
AU  - Prodanovic, Radivoje
AU  - Djurdjevic Djelmas, Aleksandra
AU  - Kalicanin, Nevena
AU  - Zlatovic, Mario
AU  - Sladic, Dusan
AU  - Vallet, Thomas
AU  - Vignuzzi, Marco
AU  - Saicic, Radomir N.
PY  - 2024
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6475
AB  - We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.
PB  - Taylor and Francis Group
T2  - Journal of Enzyme Inhibition and Medicinal Chemistry
T1  - Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies
VL  - 39
IS  - 1
SP  - 2289007
DO  - 10.1080/14756366.2023.2289007
ER  - 

@article{
author = "Ferjancic, Zorana and Bihelovic, Filip and Vulovic, Bojan and Matovic, Radomir and Trmcic, Milena and Jankovic, Aleksandar and Pavlovic, Milos and Djurkovic, Filip and Prodanovic, Radivoje and Djurdjevic Djelmas, Aleksandra and Kalicanin, Nevena and Zlatovic, Mario and Sladic, Dusan and Vallet, Thomas and Vignuzzi, Marco and Saicic, Radomir N.",
year = "2024",
abstract = "We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections.",
publisher = "Taylor and Francis Group",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
title = "Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies",
volume = "39",
number = "1",
pages = "2289007",
doi = "10.1080/14756366.2023.2289007"
}

Ferjancic, Z., Bihelovic, F., Vulovic, B., Matovic, R., Trmcic, M., Jankovic, A., Pavlovic, M., Djurkovic, F., Prodanovic, R., Djurdjevic Djelmas, A., Kalicanin, N., Zlatovic, M., Sladic, D., Vallet, T., Vignuzzi, M.,& Saicic, R. N.. (2024). Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies. in Journal of Enzyme Inhibition and Medicinal Chemistry
Taylor and Francis Group., 39(1), 2289007.
https://doi.org/10.1080/14756366.2023.2289007

Ferjancic Z, Bihelovic F, Vulovic B, Matovic R, Trmcic M, Jankovic A, Pavlovic M, Djurkovic F, Prodanovic R, Djurdjevic Djelmas A, Kalicanin N, Zlatovic M, Sladic D, Vallet T, Vignuzzi M, Saicic RN. Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2024;39(1):2289007.
doi:10.1080/14756366.2023.2289007 .

Ferjancic, Zorana, Bihelovic, Filip, Vulovic, Bojan, Matovic, Radomir, Trmcic, Milena, Jankovic, Aleksandar, Pavlovic, Milos, Djurkovic, Filip, Prodanovic, Radivoje, Djurdjevic Djelmas, Aleksandra, Kalicanin, Nevena, Zlatovic, Mario, Sladic, Dusan, Vallet, Thomas, Vignuzzi, Marco, Saicic, Radomir N., "Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies" in Journal of Enzyme Inhibition and Medicinal Chemistry, 39, no. 1 (2024):2289007,
https://doi.org/10.1080/14756366.2023.2289007 . .

TY  - JOUR
AU  - Saičić, Radomir
AU  - Trmčić, Milena
PY  - 2021
UR  - http://www.doiserbia.nb.rs/Article.aspx?id=0352-51392100099S
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5044
AB  - An attempt to synthesize the cyclohexane core of antibiotic abyssomicin C is described. The initial, protecting group-free approach (relying on internal protection) failed and had to be modified, in order to allow for efficient deprotection of the acid-sensitive cyclization precursor in the penultimate synthetic step. Thus, a pyranoside structural unit was used as a latent lactone/ester functionality, which was deprotected via thioacetalization/hydrolysis/oxidation sequence, to give the δ-valerolactone-type cyclization precursor. Unfortunately, the key cyclization reaction was not feasible, even after structural modification of the cyclization precursor. Reluctance towards cyclization turned out to be a general property of (at least some) Δ7-unsaturated esters, which required the development of a new strategy for this type of transformation.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - A study towards the synthesis of (-)-atrop-abyssomicin C core
VL  - 86
IS  - 12
SP  - 1305
EP  - 1315
DO  - 10.2298/JSC211001099S
ER  - 

@article{
author = "Saičić, Radomir and Trmčić, Milena",
year = "2021",
abstract = "An attempt to synthesize the cyclohexane core of antibiotic abyssomicin C is described. The initial, protecting group-free approach (relying on internal protection) failed and had to be modified, in order to allow for efficient deprotection of the acid-sensitive cyclization precursor in the penultimate synthetic step. Thus, a pyranoside structural unit was used as a latent lactone/ester functionality, which was deprotected via thioacetalization/hydrolysis/oxidation sequence, to give the δ-valerolactone-type cyclization precursor. Unfortunately, the key cyclization reaction was not feasible, even after structural modification of the cyclization precursor. Reluctance towards cyclization turned out to be a general property of (at least some) Δ7-unsaturated esters, which required the development of a new strategy for this type of transformation.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society, Journal of the Serbian Chemical Society",
title = "A study towards the synthesis of (-)-atrop-abyssomicin C core",
volume = "86",
number = "12",
pages = "1305-1315",
doi = "10.2298/JSC211001099S"
}

Saičić, R.,& Trmčić, M.. (2021). A study towards the synthesis of (-)-atrop-abyssomicin C core. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 86(12), 1305-1315.
https://doi.org/10.2298/JSC211001099S

Saičić R, Trmčić M. A study towards the synthesis of (-)-atrop-abyssomicin C core. in Journal of the Serbian Chemical Society. 2021;86(12):1305-1315.
doi:10.2298/JSC211001099S .

Saičić, Radomir, Trmčić, Milena, "A study towards the synthesis of (-)-atrop-abyssomicin C core" in Journal of the Serbian Chemical Society, 86, no. 12 (2021):1305-1315,
https://doi.org/10.2298/JSC211001099S . .

TY  - JOUR
AU  - Vulović, Bojan
AU  - Trmčić, Milena
AU  - Matović, Radomir
AU  - Saičić, Radomir
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3819
AB  - Unsaturated oxyallyl cations with a suitably positioned alkene bond undergo 5-exo-cyclization with the formation of vinylcyclopentane derivatives. Alkyne analogues provide allenes. The reaction proceeds with a moderate to excellent level of stereoselectivity and allows for asymmetric induction in the reaction with chiral substrate.
PB  - ACS
T2  - Organic Letters
T1  - Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation
VL  - 21
IS  - 23
SP  - 9618
EP  - 9621
DO  - 10.1021/acs.orglett.9b03791
ER  - 

@article{
author = "Vulović, Bojan and Trmčić, Milena and Matović, Radomir and Saičić, Radomir",
year = "2019",
abstract = "Unsaturated oxyallyl cations with a suitably positioned alkene bond undergo 5-exo-cyclization with the formation of vinylcyclopentane derivatives. Alkyne analogues provide allenes. The reaction proceeds with a moderate to excellent level of stereoselectivity and allows for asymmetric induction in the reaction with chiral substrate.",
publisher = "ACS",
journal = "Organic Letters",
title = "Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation",
volume = "21",
number = "23",
pages = "9618-9621",
doi = "10.1021/acs.orglett.9b03791"
}

Vulović, B., Trmčić, M., Matović, R.,& Saičić, R.. (2019). Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. in Organic Letters
ACS., 21(23), 9618-9621.
https://doi.org/10.1021/acs.orglett.9b03791

Vulović B, Trmčić M, Matović R, Saičić R. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. in Organic Letters. 2019;21(23):9618-9621.
doi:10.1021/acs.orglett.9b03791 .

Vulović, Bojan, Trmčić, Milena, Matović, Radomir, Saičić, Radomir, "Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation" in Organic Letters, 21, no. 23 (2019):9618-9621,
https://doi.org/10.1021/acs.orglett.9b03791 . .

TY  - DATA
AU  - Vulović, Bojan
AU  - Trmčić, Milena
AU  - Matović, Radomir
AU  - Saičić, Radomir
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3841
PB  - ACS
T2  - Organic Letters
T1  - Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3841
ER  - 

@misc{
author = "Vulović, Bojan and Trmčić, Milena and Matović, Radomir and Saičić, Radomir",
year = "2019",
publisher = "ACS",
journal = "Organic Letters",
title = "Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3841"
}

Vulović, B., Trmčić, M., Matović, R.,& Saičić, R.. (2019). Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791. in Organic Letters
ACS..
https://hdl.handle.net/21.15107/rcub_cherry_3841

Vulović B, Trmčić M, Matović R, Saičić R. Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791. in Organic Letters. 2019;.
https://hdl.handle.net/21.15107/rcub_cherry_3841 .

Vulović, Bojan, Trmčić, Milena, Matović, Radomir, Saičić, Radomir, "Supplementary data for the article: Vulovic, B.; Trmcic, M.; Matovic, R.; Saicic, R. N. Cyclization Reactions of Oxyallyl Cation. A Method for Cyclopentane Ring Formation. Organic Letters 2019, 21 (23), 9618–9621. https://doi.org/10.1021/acs.orglett.9b03791" in Organic Letters (2019),
https://hdl.handle.net/21.15107/rcub_cherry_3841 .

TY  - JOUR
AU  - Novković, Luka P.
AU  - Trmčić, Milena
AU  - Rodić, Marko
AU  - Bihelović, Filip
AU  - Zlatar, Matija
AU  - Matović, Radomir
AU  - Saičić, Radomir
PY  - 2015
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2000
AB  - Domino reactions of ketones with molecular oxygen in the presence of potassium hydroxide and potassium t-butoxide afford cyclic hydroperoxy acetals (3,5-dihydroxy-1,2-dioxanes). Mixed endoperoxides can also be obtained in a three-component reaction of two ketones and oxygen.
PB  - Royal Soc Chemistry, Cambridge
T2  - RSC Advances
T1  - Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen
VL  - 5
IS  - 120
SP  - 99577
EP  - 99584
DO  - 10.1039/c5ra13476e
ER  - 

@article{
author = "Novković, Luka P. and Trmčić, Milena and Rodić, Marko and Bihelović, Filip and Zlatar, Matija and Matović, Radomir and Saičić, Radomir",
year = "2015",
abstract = "Domino reactions of ketones with molecular oxygen in the presence of potassium hydroxide and potassium t-butoxide afford cyclic hydroperoxy acetals (3,5-dihydroxy-1,2-dioxanes). Mixed endoperoxides can also be obtained in a three-component reaction of two ketones and oxygen.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "RSC Advances",
title = "Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen",
volume = "5",
number = "120",
pages = "99577-99584",
doi = "10.1039/c5ra13476e"
}

Novković, L. P., Trmčić, M., Rodić, M., Bihelović, F., Zlatar, M., Matović, R.,& Saičić, R.. (2015). Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen. in RSC Advances
Royal Soc Chemistry, Cambridge., 5(120), 99577-99584.
https://doi.org/10.1039/c5ra13476e

Novković LP, Trmčić M, Rodić M, Bihelović F, Zlatar M, Matović R, Saičić R. Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen. in RSC Advances. 2015;5(120):99577-99584.
doi:10.1039/c5ra13476e .

Novković, Luka P., Trmčić, Milena, Rodić, Marko, Bihelović, Filip, Zlatar, Matija, Matović, Radomir, Saičić, Radomir, "Synthesis of endoperoxides by domino reactions of ketones and molecular oxygen" in RSC Advances, 5, no. 120 (2015):99577-99584,
https://doi.org/10.1039/c5ra13476e . .

TY  - DATA
AU  - Novković, Luka P.
AU  - Trmčić, Milena
AU  - Rodić, Marko
AU  - Bihelović, Filip
AU  - Zlatar, Matija
AU  - Matović, Radomir
AU  - Saičić, Radomir
PY  - 2015
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3442
PB  - Royal Soc Chemistry, Cambridge
T2  - RSC Advances
T1  - Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3442
ER  - 

@misc{
author = "Novković, Luka P. and Trmčić, Milena and Rodić, Marko and Bihelović, Filip and Zlatar, Matija and Matović, Radomir and Saičić, Radomir",
year = "2015",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "RSC Advances",
title = "Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3442"
}

Novković, L. P., Trmčić, M., Rodić, M., Bihelović, F., Zlatar, M., Matović, R.,& Saičić, R.. (2015). Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e. in RSC Advances
Royal Soc Chemistry, Cambridge..
https://hdl.handle.net/21.15107/rcub_cherry_3442

Novković LP, Trmčić M, Rodić M, Bihelović F, Zlatar M, Matović R, Saičić R. Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e. in RSC Advances. 2015;.
https://hdl.handle.net/21.15107/rcub_cherry_3442 .

Novković, Luka P., Trmčić, Milena, Rodić, Marko, Bihelović, Filip, Zlatar, Matija, Matović, Radomir, Saičić, Radomir, "Supplementary data for article: Novkovic, L.; Trmcic, M.; Rodic, M.; Bihelovic, F.; Zlatar, M.; Matovic, R.; Saicic, R. N. Synthesis of Endoperoxides by Domino Reactions of Ketones and Molecular Oxygen. RSC Advances 2015, 5 (120), 99577–99584. https://doi.org/10.1039/c5ra13476e" in RSC Advances (2015),
https://hdl.handle.net/21.15107/rcub_cherry_3442 .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Chadbourne, Frances L.
AU  - Brear, Paul M.
AU  - Denny, Paul W.
AU  - Cobb, Steven L.
AU  - Hodgson, David R. W.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1620
AB  - We recently reported the use of PSCl3 for the thiophosphorylation of alkylamines where the resulting N-thiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156-6158.). Herein we report the development of this methodology using amino acid, amino sugar, aminonucleoside and aniline substrates. The hydrolysis properties of N-thiophosphoramidate ions and their reactivities towards alkylating agents are also explored. In addition, we demonstrate the application of our approach to the preparation of a small library of compounds, including quinoline-based N,S-dialkylthiophosphoramidates which were tested for antileishmanial activity.
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing
VL  - 11
IS  - 16
SP  - 2660
EP  - 2675
DO  - 10.1039/c3ob27448a
ER  - 

@article{
author = "Trmčić, Milena and Chadbourne, Frances L. and Brear, Paul M. and Denny, Paul W. and Cobb, Steven L. and Hodgson, David R. W.",
year = "2013",
abstract = "We recently reported the use of PSCl3 for the thiophosphorylation of alkylamines where the resulting N-thiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156-6158.). Herein we report the development of this methodology using amino acid, amino sugar, aminonucleoside and aniline substrates. The hydrolysis properties of N-thiophosphoramidate ions and their reactivities towards alkylating agents are also explored. In addition, we demonstrate the application of our approach to the preparation of a small library of compounds, including quinoline-based N,S-dialkylthiophosphoramidates which were tested for antileishmanial activity.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing",
volume = "11",
number = "16",
pages = "2660-2675",
doi = "10.1039/c3ob27448a"
}

Trmčić, M., Chadbourne, F. L., Brear, P. M., Denny, P. W., Cobb, S. L.,& Hodgson, D. R. W.. (2013). Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge., 11(16), 2660-2675.
https://doi.org/10.1039/c3ob27448a

Trmčić M, Chadbourne FL, Brear PM, Denny PW, Cobb SL, Hodgson DRW. Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. in Organic and Biomolecular Chemistry. 2013;11(16):2660-2675.
doi:10.1039/c3ob27448a .

Trmčić, Milena, Chadbourne, Frances L., Brear, Paul M., Denny, Paul W., Cobb, Steven L., Hodgson, David R. W., "Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing" in Organic and Biomolecular Chemistry, 11, no. 16 (2013):2660-2675,
https://doi.org/10.1039/c3ob27448a . .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Chadbourne, Frances L.
AU  - Brear, Paul M.
AU  - Denny, Paul W.
AU  - Cobb, Steven L.
AU  - Hodgson, David R. W.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2821
AB  - We recently reported the use of PSCl3 for the thiophosphorylation of alkylamines where the resulting N-thiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156-6158.). Herein we report the development of this methodology using amino acid, amino sugar, aminonucleoside and aniline substrates. The hydrolysis properties of N-thiophosphoramidate ions and their reactivities towards alkylating agents are also explored. In addition, we demonstrate the application of our approach to the preparation of a small library of compounds, including quinoline-based N,S-dialkylthiophosphoramidates which were tested for antileishmanial activity.
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing
VL  - 11
IS  - 16
SP  - 2660
EP  - 2675
DO  - 10.1039/c3ob27448a
ER  - 

@article{
author = "Trmčić, Milena and Chadbourne, Frances L. and Brear, Paul M. and Denny, Paul W. and Cobb, Steven L. and Hodgson, David R. W.",
year = "2013",
abstract = "We recently reported the use of PSCl3 for the thiophosphorylation of alkylamines where the resulting N-thiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156-6158.). Herein we report the development of this methodology using amino acid, amino sugar, aminonucleoside and aniline substrates. The hydrolysis properties of N-thiophosphoramidate ions and their reactivities towards alkylating agents are also explored. In addition, we demonstrate the application of our approach to the preparation of a small library of compounds, including quinoline-based N,S-dialkylthiophosphoramidates which were tested for antileishmanial activity.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing",
volume = "11",
number = "16",
pages = "2660-2675",
doi = "10.1039/c3ob27448a"
}

Trmčić, M., Chadbourne, F. L., Brear, P. M., Denny, P. W., Cobb, S. L.,& Hodgson, D. R. W.. (2013). Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge., 11(16), 2660-2675.
https://doi.org/10.1039/c3ob27448a

Trmčić M, Chadbourne FL, Brear PM, Denny PW, Cobb SL, Hodgson DRW. Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. in Organic and Biomolecular Chemistry. 2013;11(16):2660-2675.
doi:10.1039/c3ob27448a .

Trmčić, Milena, Chadbourne, Frances L., Brear, Paul M., Denny, Paul W., Cobb, Steven L., Hodgson, David R. W., "Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing" in Organic and Biomolecular Chemistry, 11, no. 16 (2013):2660-2675,
https://doi.org/10.1039/c3ob27448a . .

TY  - DATA
AU  - Trmčić, Milena
AU  - Chadbourne, Frances L.
AU  - Brear, Paul M.
AU  - Denny, Paul W.
AU  - Cobb, Steven L.
AU  - Hodgson, David R. W.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3468
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - Supplementary data for article: Trmčić, M.; Chadbourne, F. L.; Brear, P. M.; Denny, P. W.; Cobb, S. L.; Hodgson, D. R. W. Aqueous Synthesis of N,S-Dialkylthiophosphoramidates: Design, Optimisation and Application to Library Construction and Antileishmanial Testing. Organic and Biomolecular Chemistry 2013, 11 (16), 2660–2675. https://doi.org/10.1039/c3ob27448a
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3468
ER  - 

@misc{
author = "Trmčić, Milena and Chadbourne, Frances L. and Brear, Paul M. and Denny, Paul W. and Cobb, Steven L. and Hodgson, David R. W.",
year = "2013",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "Supplementary data for article: Trmčić, M.; Chadbourne, F. L.; Brear, P. M.; Denny, P. W.; Cobb, S. L.; Hodgson, D. R. W. Aqueous Synthesis of N,S-Dialkylthiophosphoramidates: Design, Optimisation and Application to Library Construction and Antileishmanial Testing. Organic and Biomolecular Chemistry 2013, 11 (16), 2660–2675. https://doi.org/10.1039/c3ob27448a",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3468"
}

Trmčić, M., Chadbourne, F. L., Brear, P. M., Denny, P. W., Cobb, S. L.,& Hodgson, D. R. W.. (2013). Supplementary data for article: Trmčić, M.; Chadbourne, F. L.; Brear, P. M.; Denny, P. W.; Cobb, S. L.; Hodgson, D. R. W. Aqueous Synthesis of N,S-Dialkylthiophosphoramidates: Design, Optimisation and Application to Library Construction and Antileishmanial Testing. Organic and Biomolecular Chemistry 2013, 11 (16), 2660–2675. https://doi.org/10.1039/c3ob27448a. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge..
https://hdl.handle.net/21.15107/rcub_cherry_3468

Trmčić M, Chadbourne FL, Brear PM, Denny PW, Cobb SL, Hodgson DRW. Supplementary data for article: Trmčić, M.; Chadbourne, F. L.; Brear, P. M.; Denny, P. W.; Cobb, S. L.; Hodgson, D. R. W. Aqueous Synthesis of N,S-Dialkylthiophosphoramidates: Design, Optimisation and Application to Library Construction and Antileishmanial Testing. Organic and Biomolecular Chemistry 2013, 11 (16), 2660–2675. https://doi.org/10.1039/c3ob27448a. in Organic and Biomolecular Chemistry. 2013;.
https://hdl.handle.net/21.15107/rcub_cherry_3468 .

Trmčić, Milena, Chadbourne, Frances L., Brear, Paul M., Denny, Paul W., Cobb, Steven L., Hodgson, David R. W., "Supplementary data for article: Trmčić, M.; Chadbourne, F. L.; Brear, P. M.; Denny, P. W.; Cobb, S. L.; Hodgson, D. R. W. Aqueous Synthesis of N,S-Dialkylthiophosphoramidates: Design, Optimisation and Application to Library Construction and Antileishmanial Testing. Organic and Biomolecular Chemistry 2013, 11 (16), 2660–2675. https://doi.org/10.1039/c3ob27448a" in Organic and Biomolecular Chemistry (2013),
https://hdl.handle.net/21.15107/rcub_cherry_3468 .

TY  - DATA
AU  - Trmčić, Milena
AU  - Matović, Radomir
AU  - Tovilović, Gordana
AU  - Ristić, Biljana Z.
AU  - Trajković, Vladimir S.
AU  - Ferjančić, Zorana
AU  - Saičić, Radomir
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3673
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3673
ER  - 

@misc{
author = "Trmčić, Milena and Matović, Radomir and Tovilović, Gordana and Ristić, Biljana Z. and Trajković, Vladimir S. and Ferjančić, Zorana and Saičić, Radomir",
year = "2012",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3673"
}

Trmčić, M., Matović, R., Tovilović, G., Ristić, B. Z., Trajković, V. S., Ferjančić, Z.,& Saičić, R.. (2012). Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge..
https://hdl.handle.net/21.15107/rcub_cherry_3673

Trmčić M, Matović R, Tovilović G, Ristić BZ, Trajković VS, Ferjančić Z, Saičić R. Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f. in Organic and Biomolecular Chemistry. 2012;.
https://hdl.handle.net/21.15107/rcub_cherry_3673 .

Trmčić, Milena, Matović, Radomir, Tovilović, Gordana, Ristić, Biljana Z., Trajković, Vladimir S., Ferjančić, Zorana, Saičić, Radomir, "Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f" in Organic and Biomolecular Chemistry (2012),
https://hdl.handle.net/21.15107/rcub_cherry_3673 .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Matović, Radomir
AU  - Tovilović, Gordana
AU  - Ristić, Biljana Z.
AU  - Trajković, Vladimir S.
AU  - Ferjančić, Zorana
AU  - Saičić, Radomir
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1304
AB  - The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids
VL  - 10
IS  - 25
SP  - 4933
EP  - 4942
DO  - 10.1039/c2ob25514f
ER  - 

@article{
author = "Trmčić, Milena and Matović, Radomir and Tovilović, Gordana and Ristić, Biljana Z. and Trajković, Vladimir S. and Ferjančić, Zorana and Saičić, Radomir",
year = "2012",
abstract = "The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids",
volume = "10",
number = "25",
pages = "4933-4942",
doi = "10.1039/c2ob25514f"
}

Trmčić, M., Matović, R., Tovilović, G., Ristić, B. Z., Trajković, V. S., Ferjančić, Z.,& Saičić, R.. (2012). A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge., 10(25), 4933-4942.
https://doi.org/10.1039/c2ob25514f

Trmčić M, Matović R, Tovilović G, Ristić BZ, Trajković VS, Ferjančić Z, Saičić R. A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. in Organic and Biomolecular Chemistry. 2012;10(25):4933-4942.
doi:10.1039/c2ob25514f .

Trmčić, Milena, Matović, Radomir, Tovilović, Gordana, Ristić, Biljana Z., Trajković, Vladimir S., Ferjančić, Zorana, Saičić, Radomir, "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids" in Organic and Biomolecular Chemistry, 10, no. 25 (2012):4933-4942,
https://doi.org/10.1039/c2ob25514f . .

TY  - JOUR
AU  - Farquhar, Erik R.
AU  - Emerson, Joseph P.
AU  - Koehntop, Kevin D.
AU  - Reynolds, Mark F.
AU  - Trmčić, Milena
AU  - Que, Jr., Lawrence
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1335
AB  - The homoprotocatechuate 2,3-dioxygenase from Arthrobacter globiformis (MndD) catalyzes the oxidative ring cleavage reaction of its catechol substrate in an extradiol fashion. Although this reactivity is more typically associated with non-heme iron enzymes, MndD exhibits an unusual specificity for manganese(II). MndD is structurally very similar to the iron(II)-dependent homoprotocatechuate 2,3-dioxygenase from Brevibacterium fuscum (HPCD), and we have previously shown that both MndD and HPCD are equally active towards substrate turnover with either iron(II) or manganese(11) (Emerson et al. in Proc. Natl. Acad. Sci. USA 105:7347-7352, 2008). However, expression of MndD in Escherichia coli under aerobic conditions in the presence of excess iron results in the isolation of inactive blue-green iron-substituted MndD. Spectroscopic studies indicate that this form of iron-substituted MndD contains an iron(III) center with abound catecholate, which is presumably generated by in vivo self-hydroxylation of a second-sphere tyrosine residue, as found for other self-hydroxylated non-heme iron oxygenases. The absence of this modification in either the native manganese-containing MndD or iron-containing HPCD suggests that the metal center of iron-substituted MndD is able to bind and activate 02 in the absence of its substrate, employing a high-valence oxoiron oxidant to carry out the observed self-hydroxylation chemistry. These results demonstrate that the active site metal in MndD can support two dramatically different 02 activation pathways, further highlighting the catalytic flexibility of enzymes containing a 2-His-1-carboxylate facial triad metal binding motif.
PB  - Springer, New York
T2  - Journal of Biological Inorganic Chemistry
T1  - In vivo self-hydroxylation of an iron-substituted manganese-dependent extradiol cleaving catechol dioxygenase
VL  - 16
IS  - 4
SP  - 589
EP  - 597
DO  - 10.1007/s00775-011-0760-4
ER  - 

@article{
author = "Farquhar, Erik R. and Emerson, Joseph P. and Koehntop, Kevin D. and Reynolds, Mark F. and Trmčić, Milena and Que, Jr., Lawrence",
year = "2011",
abstract = "The homoprotocatechuate 2,3-dioxygenase from Arthrobacter globiformis (MndD) catalyzes the oxidative ring cleavage reaction of its catechol substrate in an extradiol fashion. Although this reactivity is more typically associated with non-heme iron enzymes, MndD exhibits an unusual specificity for manganese(II). MndD is structurally very similar to the iron(II)-dependent homoprotocatechuate 2,3-dioxygenase from Brevibacterium fuscum (HPCD), and we have previously shown that both MndD and HPCD are equally active towards substrate turnover with either iron(II) or manganese(11) (Emerson et al. in Proc. Natl. Acad. Sci. USA 105:7347-7352, 2008). However, expression of MndD in Escherichia coli under aerobic conditions in the presence of excess iron results in the isolation of inactive blue-green iron-substituted MndD. Spectroscopic studies indicate that this form of iron-substituted MndD contains an iron(III) center with abound catecholate, which is presumably generated by in vivo self-hydroxylation of a second-sphere tyrosine residue, as found for other self-hydroxylated non-heme iron oxygenases. The absence of this modification in either the native manganese-containing MndD or iron-containing HPCD suggests that the metal center of iron-substituted MndD is able to bind and activate 02 in the absence of its substrate, employing a high-valence oxoiron oxidant to carry out the observed self-hydroxylation chemistry. These results demonstrate that the active site metal in MndD can support two dramatically different 02 activation pathways, further highlighting the catalytic flexibility of enzymes containing a 2-His-1-carboxylate facial triad metal binding motif.",
publisher = "Springer, New York",
journal = "Journal of Biological Inorganic Chemistry",
title = "In vivo self-hydroxylation of an iron-substituted manganese-dependent extradiol cleaving catechol dioxygenase",
volume = "16",
number = "4",
pages = "589-597",
doi = "10.1007/s00775-011-0760-4"
}

Farquhar, E. R., Emerson, J. P., Koehntop, K. D., Reynolds, M. F., Trmčić, M.,& Que, Jr., L.. (2011). In vivo self-hydroxylation of an iron-substituted manganese-dependent extradiol cleaving catechol dioxygenase. in Journal of Biological Inorganic Chemistry
Springer, New York., 16(4), 589-597.
https://doi.org/10.1007/s00775-011-0760-4

Farquhar ER, Emerson JP, Koehntop KD, Reynolds MF, Trmčić M, Que JL. In vivo self-hydroxylation of an iron-substituted manganese-dependent extradiol cleaving catechol dioxygenase. in Journal of Biological Inorganic Chemistry. 2011;16(4):589-597.
doi:10.1007/s00775-011-0760-4 .

Farquhar, Erik R., Emerson, Joseph P., Koehntop, Kevin D., Reynolds, Mark F., Trmčić, Milena, Que, Jr., Lawrence, "In vivo self-hydroxylation of an iron-substituted manganese-dependent extradiol cleaving catechol dioxygenase" in Journal of Biological Inorganic Chemistry, 16, no. 4 (2011):589-597,
https://doi.org/10.1007/s00775-011-0760-4 . .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Hodgson, David R. W.
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1344
AB  - An aqueous method for the preparation of N,S-dialkyl thiophosphoramidates is reported. Thiophosphorylation of alkylamines was performed using SPCl3 in aqueous reaction media, and the resulting thiophosphoramidate-S-anions were S-alkylated with soft electrophiles. Ranges of amines and electrophiles were explored.
PB  - Royal Soc Chemistry, Cambridge
T2  - Chemical Communications
T1  - Synthesis of thiophosphoramidates in water: Click chemistry for phosphates
VL  - 47
IS  - 21
SP  - 6156
EP  - 6158
DO  - 10.1039/c1cc11586c
ER  - 

@article{
author = "Trmčić, Milena and Hodgson, David R. W.",
year = "2011",
abstract = "An aqueous method for the preparation of N,S-dialkyl thiophosphoramidates is reported. Thiophosphorylation of alkylamines was performed using SPCl3 in aqueous reaction media, and the resulting thiophosphoramidate-S-anions were S-alkylated with soft electrophiles. Ranges of amines and electrophiles were explored.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Chemical Communications",
title = "Synthesis of thiophosphoramidates in water: Click chemistry for phosphates",
volume = "47",
number = "21",
pages = "6156-6158",
doi = "10.1039/c1cc11586c"
}

Trmčić, M.,& Hodgson, D. R. W.. (2011). Synthesis of thiophosphoramidates in water: Click chemistry for phosphates. in Chemical Communications
Royal Soc Chemistry, Cambridge., 47(21), 6156-6158.
https://doi.org/10.1039/c1cc11586c

Trmčić M, Hodgson DRW. Synthesis of thiophosphoramidates in water: Click chemistry for phosphates. in Chemical Communications. 2011;47(21):6156-6158.
doi:10.1039/c1cc11586c .

Trmčić, Milena, Hodgson, David R. W., "Synthesis of thiophosphoramidates in water: Click chemistry for phosphates" in Chemical Communications, 47, no. 21 (2011):6156-6158,
https://doi.org/10.1039/c1cc11586c . .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Hodgson, David R. W.
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2819
AB  - An aqueous method for the preparation of N,S-dialkyl thiophosphoramidates is reported. Thiophosphorylation of alkylamines was performed using SPCl3 in aqueous reaction media, and the resulting thiophosphoramidate-S-anions were S-alkylated with soft electrophiles. Ranges of amines and electrophiles were explored.
PB  - Royal Soc Chemistry, Cambridge
T2  - Chemical Communications
T1  - Synthesis of thiophosphoramidates in water: Click chemistry for phosphates
VL  - 47
IS  - 21
SP  - 6156
EP  - 6158
DO  - 10.1039/c1cc11586c
ER  - 

@article{
author = "Trmčić, Milena and Hodgson, David R. W.",
year = "2011",
abstract = "An aqueous method for the preparation of N,S-dialkyl thiophosphoramidates is reported. Thiophosphorylation of alkylamines was performed using SPCl3 in aqueous reaction media, and the resulting thiophosphoramidate-S-anions were S-alkylated with soft electrophiles. Ranges of amines and electrophiles were explored.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Chemical Communications",
title = "Synthesis of thiophosphoramidates in water: Click chemistry for phosphates",
volume = "47",
number = "21",
pages = "6156-6158",
doi = "10.1039/c1cc11586c"
}

Trmčić, M.,& Hodgson, D. R. W.. (2011). Synthesis of thiophosphoramidates in water: Click chemistry for phosphates. in Chemical Communications
Royal Soc Chemistry, Cambridge., 47(21), 6156-6158.
https://doi.org/10.1039/c1cc11586c

Trmčić M, Hodgson DRW. Synthesis of thiophosphoramidates in water: Click chemistry for phosphates. in Chemical Communications. 2011;47(21):6156-6158.
doi:10.1039/c1cc11586c .

Trmčić, Milena, Hodgson, David R. W., "Synthesis of thiophosphoramidates in water: Click chemistry for phosphates" in Chemical Communications, 47, no. 21 (2011):6156-6158,
https://doi.org/10.1039/c1cc11586c . .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Hodgson, David R. W.
PY  - 2010
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1108
AB  - Background: Heterobifunctional cross-linking agents are useful in both protein science and organic synthesis. Aminolysis of reactive esters in aqueous systems is often used in bioconjugation chemistry, but it must compete against hydrolysis processes. Here we study the kinetics of aminolysis and hydrolysis of 2-S-phosphorylacetate ester intermediates that result from displacement of bromide by a thiophosphate nucleophile from commonly used bromoacetate ester cross-linking agents. Results: We found cross-linking between uridine-5'-monophosphorothioate and D-glucosamine using N-hydroxybenzotriazole and N-hydroxysuccinimde bromoacetates to be ineffective. In order to gain insight into these shortfalls, 2-S-(5'-thiophosphoryluridine)acetic acid esters were prepared using p-nitrophenyl bromoacetate or m-nitrophenyl bromoacetate in combination with uridine-5'-monophosphorothioate. Kinetics of hydrolysis and aminolysis of the resulting p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates were determined by monitoring the formation of phenolate ions spectrophotometrically as a function of pH. The p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates showed similar reactivity profiles despite the significant difference in the pK(aH) values of their nitrophenolate leaving groups. Both were more reactive with respect to hydrolysis and aminolysis in comparison to their simple acetate progenitors, but their calculated selectivity towards aminolysis vs hydrolysis, while reasonable, would not lead to clean reactions that do not require purification. Extrapolations of the kinetic data were used to predict leaving group pK(a) values that could lead to improved selectivity towards aminolysis while retaining reasonable reaction times. Conclusions: Both p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates show some selectivity towards aminolysis over hydrolysis, with the m-nitrophenolate system displaying slightly better selectivity. Extrapolation of the data for hydrolysis and aminolysis of these esters suggests that the use of readily accessible trifluoroethyl 2-S-(5'-thiophosphoryluridine)acetate with a leaving group pK(aH) of 12.4 should afford better selectivity while maintaining reasonable reaction times. Kinetically, p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates show similar properties to o-nitrophenyl 2-S-ethylacetate, and show no evidence for intramolecular catalysis of hydrolysis or aminolysis by the phosphoryl groups.
PB  - Beilstein-Institut, Frankfurt Am Main
T2  - Beilstein Journal of Organic Chemistry
T1  - Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates
VL  - 6
SP  - 732
EP  - 741
DO  - 10.3762/bjoc.6.87
ER  - 

@article{
author = "Trmčić, Milena and Hodgson, David R. W.",
year = "2010",
abstract = "Background: Heterobifunctional cross-linking agents are useful in both protein science and organic synthesis. Aminolysis of reactive esters in aqueous systems is often used in bioconjugation chemistry, but it must compete against hydrolysis processes. Here we study the kinetics of aminolysis and hydrolysis of 2-S-phosphorylacetate ester intermediates that result from displacement of bromide by a thiophosphate nucleophile from commonly used bromoacetate ester cross-linking agents. Results: We found cross-linking between uridine-5'-monophosphorothioate and D-glucosamine using N-hydroxybenzotriazole and N-hydroxysuccinimde bromoacetates to be ineffective. In order to gain insight into these shortfalls, 2-S-(5'-thiophosphoryluridine)acetic acid esters were prepared using p-nitrophenyl bromoacetate or m-nitrophenyl bromoacetate in combination with uridine-5'-monophosphorothioate. Kinetics of hydrolysis and aminolysis of the resulting p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates were determined by monitoring the formation of phenolate ions spectrophotometrically as a function of pH. The p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates showed similar reactivity profiles despite the significant difference in the pK(aH) values of their nitrophenolate leaving groups. Both were more reactive with respect to hydrolysis and aminolysis in comparison to their simple acetate progenitors, but their calculated selectivity towards aminolysis vs hydrolysis, while reasonable, would not lead to clean reactions that do not require purification. Extrapolations of the kinetic data were used to predict leaving group pK(a) values that could lead to improved selectivity towards aminolysis while retaining reasonable reaction times. Conclusions: Both p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates show some selectivity towards aminolysis over hydrolysis, with the m-nitrophenolate system displaying slightly better selectivity. Extrapolation of the data for hydrolysis and aminolysis of these esters suggests that the use of readily accessible trifluoroethyl 2-S-(5'-thiophosphoryluridine)acetate with a leaving group pK(aH) of 12.4 should afford better selectivity while maintaining reasonable reaction times. Kinetically, p- and m-nitrophenyl 2-S-(5'-thiophosphoryluridine)acetates show similar properties to o-nitrophenyl 2-S-ethylacetate, and show no evidence for intramolecular catalysis of hydrolysis or aminolysis by the phosphoryl groups.",
publisher = "Beilstein-Institut, Frankfurt Am Main",
journal = "Beilstein Journal of Organic Chemistry",
title = "Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates",
volume = "6",
pages = "732-741",
doi = "10.3762/bjoc.6.87"
}

Trmčić, M.,& Hodgson, D. R. W.. (2010). Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates. in Beilstein Journal of Organic Chemistry
Beilstein-Institut, Frankfurt Am Main., 6, 732-741.
https://doi.org/10.3762/bjoc.6.87

Trmčić M, Hodgson DRW. Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates. in Beilstein Journal of Organic Chemistry. 2010;6:732-741.
doi:10.3762/bjoc.6.87 .

Trmčić, Milena, Hodgson, David R. W., "Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates" in Beilstein Journal of Organic Chemistry, 6 (2010):732-741,
https://doi.org/10.3762/bjoc.6.87 . .

TY  - JOUR
AU  - Brear, Paul
AU  - Freeman, Gemma R.
AU  - Shankey, Mark C.
AU  - Trmčić, Milena
AU  - Hodgson, David R. W.
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1006
AB  - We have developed simple, aqueous strategies, that avoid the use of protecting groups and chromatography, for the preparation of a series of 5'-substituted guanosine derivatives.
PB  - Royal Soc Chemistry, Cambridge
T2  - Chemical Communications
T1  - Aqueous methods for the preparation of 5 '-substituted guanosine derivatives
IS  - 33
SP  - 4980
EP  - 4981
DO  - 10.1039/b908727c
ER  - 

@article{
author = "Brear, Paul and Freeman, Gemma R. and Shankey, Mark C. and Trmčić, Milena and Hodgson, David R. W.",
year = "2009",
abstract = "We have developed simple, aqueous strategies, that avoid the use of protecting groups and chromatography, for the preparation of a series of 5'-substituted guanosine derivatives.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Chemical Communications",
title = "Aqueous methods for the preparation of 5 '-substituted guanosine derivatives",
number = "33",
pages = "4980-4981",
doi = "10.1039/b908727c"
}

Brear, P., Freeman, G. R., Shankey, M. C., Trmčić, M.,& Hodgson, D. R. W.. (2009). Aqueous methods for the preparation of 5 '-substituted guanosine derivatives. in Chemical Communications
Royal Soc Chemistry, Cambridge.(33), 4980-4981.
https://doi.org/10.1039/b908727c

Brear P, Freeman GR, Shankey MC, Trmčić M, Hodgson DRW. Aqueous methods for the preparation of 5 '-substituted guanosine derivatives. in Chemical Communications. 2009;(33):4980-4981.
doi:10.1039/b908727c .

Brear, Paul, Freeman, Gemma R., Shankey, Mark C., Trmčić, Milena, Hodgson, David R. W., "Aqueous methods for the preparation of 5 '-substituted guanosine derivatives" in Chemical Communications, no. 33 (2009):4980-4981,
https://doi.org/10.1039/b908727c . .