Tadeusz Gajda - Academia.edu (original) (raw)

Papers by Tadeusz Gajda

Research paper thumbnail of Boronic acid-based arginase inhibitors in cancer immunotherapy

Bioorganic & Medicinal Chemistry, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Design, Synthesis, and Evaluation of ω-(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

ChemMedChem, Jan 8, 2018

A series of 21 novel, structurally diverse ω-(isothiocyanato)alkylphosphinates and phosphine oxid... more A series of 21 novel, structurally diverse ω-(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX-5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell-cycle arrest and apoptosis. Ethyl (6-isothiocyanatohexyl)(phenyl)phosphinate (71) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide.

Research paper thumbnail of Phosphorus-containing isothiocyanate-derived mercapturic acids as a useful alternative for parental isothiocyanates in experimental oncology

Bioorganic & medicinal chemistry letters, Jan 15, 2018

A series of phosphonates, phosphinates and phosphine oxides isothiocyanate-derived mercapturic ac... more A series of phosphonates, phosphinates and phosphine oxides isothiocyanate-derived mercapturic acids were synthesized. A temperature dependence dynamic proton decoupled P NMR studies indicated that in most cases the compounds were obtained as a mixture of rotamers. Moreover, biologically relevant reversibility of mercapturic acids synthesis from the parental isothiocyanates was confirmed. All compounds were evaluated ashighly active antiproliferative agents in vitro in human colon cancer cell lines (LoVo and its doxorubicin-resistant subline LoVo/DX). The cell cycle progression and caspase-3 activity analyses revealed compounds moderate activity as apoptosis inducers and their poor influence on cell cycle progression in the LoVo cells. Our results confirm that isothiocyanate-derived mercapturic acids present a reasonable alternative for the parental compounds, and can replace them in the future studies on isothiocyanates potential as anticancer agents.

Research paper thumbnail of Investigation of the reaction of (R)-(+)- and (S)-(−)-α-methylbenzylammonium hypophosphites with benzaldehyde

Phosphorus, Sulfur, and Silicon and the Related Elements, 2017

Research paper thumbnail of ( S )-Naproxen® and ( S )-Ibuprofen® chlorides—convenient chemical derivatizing agents for the determination of the enantiomeric excess of hydroxy and aminophosphonates by 31 P NMR

Tetrahedron: Asymmetry, 2002

The acid chlorides of (S)-Naproxen ® and (S)-Ibuprofen ® are shown to be convenient chiral deriva... more The acid chlorides of (S)-Naproxen ® and (S)-Ibuprofen ® are shown to be convenient chiral derivatizing agents for determination of the enantiomeric purity of diethyl 1-hydroxy-and 2-hydroxyalkylphosphonates as well as their aminoalkylphosphonate analogues by means of 31 P NMR spectroscopy. Correlation between the phosphorus chemical shift and the absolute configuration of the 1-hydroxyalkylphosphonate is also discussed.

Research paper thumbnail of ChemInform Abstract: A Convenient One‐Pot Synthesis of Secondary Amines via Aza‐Wittig Reaction

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.

Research paper thumbnail of A new access to substituted tetraethyl N-Boc 2-aminoethylidene-1,1-bisphosphonates and phosphonyl-substituted aza-Morita–Baylis–Hillman-type adducts

Research paper thumbnail of Synthesis of Primary sec-alkylamines via nucleophilic ring-opening of N-phosphorylated aziridines

Tetrahedron, 1997

The novel ring-opening reaction of various 2-alkyl-and 2,2-dimethyl-N-(diethoxyphosphoryl)aziridi... more The novel ring-opening reaction of various 2-alkyl-and 2,2-dimethyl-N-(diethoxyphosphoryl)aziridines (1) and (10) with copper-modified Grignard reagents proceeds regiospecifically at the less hindered carbon. The diethyl N-sec-alkylphosphoramidates (2) thus obtained may efficiently be converted to primary sec-alkylamine hydrochlorides (3) by refluxing with 20% hydrochloric acid. 2,3-Disubstituted N-phosphorylated aziridines except N-phosphorylated cyclohexenimine (4) do not react under the described conditions. Coppermediated reaction of 2-phenyl-N-(diethoxyphosphoryl)aziridine (7) with Grignard reagents affords a mixture of regioisomers (8) and (9) but still with the preference of ring-opening at the carbon of lesser substitution.

Research paper thumbnail of N,N-dihalophosphoramides-XV

Tetrahedron, 1985

Abstract The addition of DCPA to several conjugated 1,3-dienes has been studied. The reaction was... more Abstract The addition of DCPA to several conjugated 1,3-dienes has been studied. The reaction was found to proceed in dichloromethane and was spontaneously or photolytically initiated depending on the structure of the dienes. N-chloro adducts, formed upon addition, could be reduced “ in situ ” with sodium sulphite solution to give the corresponding diethyl N-(chloroalkenyl)posphoroamidates. Addition of DCPA to terminal double bond 1,3-dienes (butadiene, isoprene and 2,3-dimethyl-1,3-butadiene) leads regiospecifically to ( E )-1,4-adducts. Similarly, 1,4-addition is also observed for 1,3-cyclohexadiene. Reaction of DCPA with nonterminal double bond 1,3-dienes ( trans -piperylene, 4-methyl-1,3-pentadiene, 2,5-dimethyl-2,4-hexadiene and 1,4-diphenyl-1,3-butadiene) usually affords a mixture of adducts. Spectral data and chemical transformations pertinent to the proof of structure of DCPA addition products are presented. A possible mechanism for the addition is discussed.

Research paper thumbnail of Di-t-Butyl Phosphorobromidate. A New Selective Phosphorylating Agent Containing Acid-Labile Protecting Groups

Research paper thumbnail of Phase-Transfer-Catalysed Halogenation of Di-t-butyl Phosphite. Preparation of Di-t-butyl Phosphorohalidates1

Research paper thumbnail of Highly Selective Amination of 1-Primary, 3-Secondary 1,3-Alkanediols. A New Approach to 3-Aminoalkyl 4-Nitrobenzoates

Research paper thumbnail of Phase-Transfer-CatalysedN-Alkylation of Carboxamides and Sulfonamides

Research paper thumbnail of A Convenient Synthesis of O-ETHYL-1-AMINOALKYLPHOSPHINATES

Phosphorus, Sulfur, and Silicon and the Related Elements, 1993

1-Aminoalkylphosphinates 4 have been obtained in good yields in a one-step transformation by the ... more 1-Aminoalkylphosphinates 4 have been obtained in good yields in a one-step transformation by the Mitsunobu reaction of 1-hydroxyalkylphosphinates 1 with hydrazoic acid, and subsequent treatment of the intermediate azides 2, with triphenylphosphine, followed by hydrolysis of the iminophosphoranes 3 with water.

Research paper thumbnail of New Approach to Diethyl 2-AMINOALKYLPHOSPHONATES

Phosphorus, Sulfur, and Silicon and the Related Elements, 1995

Diethyl 2-aminoalkylphosphonates 5 have been obtained in good yields in a one-step procedure empl... more Diethyl 2-aminoalkylphosphonates 5 have been obtained in good yields in a one-step procedure employing the Mitsunobu reaction of diethyl 2-hydroxyalkylphosphonates 2 with hydrazoic acid, and subsequent treatment of the intermediate azides 3 with triphenylphosphine, followed by hydrolysis of the iminophosphoranes 4 with water.

Research paper thumbnail of Differentiation of Diastereoisomers of Protected 1,2-Diaminoalkylphosphonic Acids by EI Mass Spectrometry and Density Functional Theory

Journal of the American Society for Mass Spectrometry, 2013

Research paper thumbnail of A New Approach to Allylamines and Pyrrolidines

Liebigs Annalen der Chemie, 1986

The 1,4-adducts 3a-c and 4, readily available from the reaction between diethyl N,Ndichlorophosph... more The 1,4-adducts 3a-c and 4, readily available from the reaction between diethyl N,Ndichlorophosphoramidate (1) and 1,3-dienes, were found to be convenient precursors for the efiicient synthesis of the 6-chloroallylamine hydrochlorides 5a-d and N-phosphorylated allylamines 6a-c and 7. The three-step transformation of 3a-c affords the cis-3,4-dibromopyrrolidine hydrochlorides 10a-c. The preparation of the 2,5-dihydro-IH-pyrrole hydrochlorides 11 ac and trans-3,4-dibromopyrrolidine hydrochlorides 13ac is also described. The stereochemistry of the reaction is studied. Eine neue Synthese von Allylaminen und Pyrrolidinen Die 1,4-Addukte 3 a-c und 4, leicht zuganglich aus Diethyl-N,N-dichlorphosphoramidat (1) und 1,3-Dienen, bewahren sich als Ausgangsprodukte fur eine effektive Synthese von 6-Chlorallylamin-hydrochloriden 5a-d und N-Phosphorylallylaminen 6a-c und 7. Die dreistufige Umwandlung von 3a-c fuhrt zu cis-3,4-Dibrompyrrolidin-hydrochloriden 10a-c. Weiterhin wird uber die Darstellung von 2,5-Dihydro-lH-pyrroI-hydrochloriden 11 a-c und trans-3,4-Dibrompyrrolidin-hydrochloriden 13a-c berichtet. Die Stereochemie der Reaktionen wird untersucht.

Research paper thumbnail of Microwave-assisted synthesis of dialkyl ω-azidoalkylphosphonates

Synthetic Communications, 2016

Research paper thumbnail of Isothiocyanate Strategy for the Synthesis of Quaternary α‐Amino Acids Bearing a Spirocyclic Ring System

Advanced Synthesis & Catalysis, 2018

This study demonstrates that isothiocyanates derived from α‐substituted α‐amino acids are useful ... more This study demonstrates that isothiocyanates derived from α‐substituted α‐amino acids are useful building blocks in the heteroannulation reactions with electron‐deficient olefins. The developed strategy proceeds in a cascade manner and involves Michael addition followed by a cyclization via nucleophilic addition. Target, spirocyclic heterocycles bearing either a quaternary α‐amino acid moiety or α‐aminophosphonate group have been efficiently synthesized in very high yield (up to 99%) and with excellent stereocontrol. The usefulness of heterocycles obtained has been demonstrated in selected transformations.magnified image

Research paper thumbnail of Direct, Microwave‐Assisted Synthesis of Isothiocyanates

European Journal of Organic Chemistry, 2019

A microwave‐assisted desulfuration of readily available dithiocarbamates, formed in situ from pri... more A microwave‐assisted desulfuration of readily available dithiocarbamates, formed in situ from primary amines, leading to target isothiocyanates has been developed. This efficient protocol provides a rapid, environmentally benign route to aliphatic and aromatic isothiocyanates.

Research paper thumbnail of Boronic acid-based arginase inhibitors in cancer immunotherapy

Bioorganic & Medicinal Chemistry, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Design, Synthesis, and Evaluation of ω-(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

ChemMedChem, Jan 8, 2018

A series of 21 novel, structurally diverse ω-(isothiocyanato)alkylphosphinates and phosphine oxid... more A series of 21 novel, structurally diverse ω-(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX-5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell-cycle arrest and apoptosis. Ethyl (6-isothiocyanatohexyl)(phenyl)phosphinate (71) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide.

Research paper thumbnail of Phosphorus-containing isothiocyanate-derived mercapturic acids as a useful alternative for parental isothiocyanates in experimental oncology

Bioorganic & medicinal chemistry letters, Jan 15, 2018

A series of phosphonates, phosphinates and phosphine oxides isothiocyanate-derived mercapturic ac... more A series of phosphonates, phosphinates and phosphine oxides isothiocyanate-derived mercapturic acids were synthesized. A temperature dependence dynamic proton decoupled P NMR studies indicated that in most cases the compounds were obtained as a mixture of rotamers. Moreover, biologically relevant reversibility of mercapturic acids synthesis from the parental isothiocyanates was confirmed. All compounds were evaluated ashighly active antiproliferative agents in vitro in human colon cancer cell lines (LoVo and its doxorubicin-resistant subline LoVo/DX). The cell cycle progression and caspase-3 activity analyses revealed compounds moderate activity as apoptosis inducers and their poor influence on cell cycle progression in the LoVo cells. Our results confirm that isothiocyanate-derived mercapturic acids present a reasonable alternative for the parental compounds, and can replace them in the future studies on isothiocyanates potential as anticancer agents.

Research paper thumbnail of Investigation of the reaction of (R)-(+)- and (S)-(−)-α-methylbenzylammonium hypophosphites with benzaldehyde

Phosphorus, Sulfur, and Silicon and the Related Elements, 2017

Research paper thumbnail of ( S )-Naproxen® and ( S )-Ibuprofen® chlorides—convenient chemical derivatizing agents for the determination of the enantiomeric excess of hydroxy and aminophosphonates by 31 P NMR

Tetrahedron: Asymmetry, 2002

The acid chlorides of (S)-Naproxen ® and (S)-Ibuprofen ® are shown to be convenient chiral deriva... more The acid chlorides of (S)-Naproxen ® and (S)-Ibuprofen ® are shown to be convenient chiral derivatizing agents for determination of the enantiomeric purity of diethyl 1-hydroxy-and 2-hydroxyalkylphosphonates as well as their aminoalkylphosphonate analogues by means of 31 P NMR spectroscopy. Correlation between the phosphorus chemical shift and the absolute configuration of the 1-hydroxyalkylphosphonate is also discussed.

Research paper thumbnail of ChemInform Abstract: A Convenient One‐Pot Synthesis of Secondary Amines via Aza‐Wittig Reaction

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.

Research paper thumbnail of A new access to substituted tetraethyl N-Boc 2-aminoethylidene-1,1-bisphosphonates and phosphonyl-substituted aza-Morita–Baylis–Hillman-type adducts

Research paper thumbnail of Synthesis of Primary sec-alkylamines via nucleophilic ring-opening of N-phosphorylated aziridines

Tetrahedron, 1997

The novel ring-opening reaction of various 2-alkyl-and 2,2-dimethyl-N-(diethoxyphosphoryl)aziridi... more The novel ring-opening reaction of various 2-alkyl-and 2,2-dimethyl-N-(diethoxyphosphoryl)aziridines (1) and (10) with copper-modified Grignard reagents proceeds regiospecifically at the less hindered carbon. The diethyl N-sec-alkylphosphoramidates (2) thus obtained may efficiently be converted to primary sec-alkylamine hydrochlorides (3) by refluxing with 20% hydrochloric acid. 2,3-Disubstituted N-phosphorylated aziridines except N-phosphorylated cyclohexenimine (4) do not react under the described conditions. Coppermediated reaction of 2-phenyl-N-(diethoxyphosphoryl)aziridine (7) with Grignard reagents affords a mixture of regioisomers (8) and (9) but still with the preference of ring-opening at the carbon of lesser substitution.

Research paper thumbnail of N,N-dihalophosphoramides-XV

Tetrahedron, 1985

Abstract The addition of DCPA to several conjugated 1,3-dienes has been studied. The reaction was... more Abstract The addition of DCPA to several conjugated 1,3-dienes has been studied. The reaction was found to proceed in dichloromethane and was spontaneously or photolytically initiated depending on the structure of the dienes. N-chloro adducts, formed upon addition, could be reduced “ in situ ” with sodium sulphite solution to give the corresponding diethyl N-(chloroalkenyl)posphoroamidates. Addition of DCPA to terminal double bond 1,3-dienes (butadiene, isoprene and 2,3-dimethyl-1,3-butadiene) leads regiospecifically to ( E )-1,4-adducts. Similarly, 1,4-addition is also observed for 1,3-cyclohexadiene. Reaction of DCPA with nonterminal double bond 1,3-dienes ( trans -piperylene, 4-methyl-1,3-pentadiene, 2,5-dimethyl-2,4-hexadiene and 1,4-diphenyl-1,3-butadiene) usually affords a mixture of adducts. Spectral data and chemical transformations pertinent to the proof of structure of DCPA addition products are presented. A possible mechanism for the addition is discussed.

Research paper thumbnail of Di-t-Butyl Phosphorobromidate. A New Selective Phosphorylating Agent Containing Acid-Labile Protecting Groups

Research paper thumbnail of Phase-Transfer-Catalysed Halogenation of Di-t-butyl Phosphite. Preparation of Di-t-butyl Phosphorohalidates1

Research paper thumbnail of Highly Selective Amination of 1-Primary, 3-Secondary 1,3-Alkanediols. A New Approach to 3-Aminoalkyl 4-Nitrobenzoates

Research paper thumbnail of Phase-Transfer-CatalysedN-Alkylation of Carboxamides and Sulfonamides

Research paper thumbnail of A Convenient Synthesis of O-ETHYL-1-AMINOALKYLPHOSPHINATES

Phosphorus, Sulfur, and Silicon and the Related Elements, 1993

1-Aminoalkylphosphinates 4 have been obtained in good yields in a one-step transformation by the ... more 1-Aminoalkylphosphinates 4 have been obtained in good yields in a one-step transformation by the Mitsunobu reaction of 1-hydroxyalkylphosphinates 1 with hydrazoic acid, and subsequent treatment of the intermediate azides 2, with triphenylphosphine, followed by hydrolysis of the iminophosphoranes 3 with water.

Research paper thumbnail of New Approach to Diethyl 2-AMINOALKYLPHOSPHONATES

Phosphorus, Sulfur, and Silicon and the Related Elements, 1995

Diethyl 2-aminoalkylphosphonates 5 have been obtained in good yields in a one-step procedure empl... more Diethyl 2-aminoalkylphosphonates 5 have been obtained in good yields in a one-step procedure employing the Mitsunobu reaction of diethyl 2-hydroxyalkylphosphonates 2 with hydrazoic acid, and subsequent treatment of the intermediate azides 3 with triphenylphosphine, followed by hydrolysis of the iminophosphoranes 4 with water.

Research paper thumbnail of Differentiation of Diastereoisomers of Protected 1,2-Diaminoalkylphosphonic Acids by EI Mass Spectrometry and Density Functional Theory

Journal of the American Society for Mass Spectrometry, 2013

Research paper thumbnail of A New Approach to Allylamines and Pyrrolidines

Liebigs Annalen der Chemie, 1986

The 1,4-adducts 3a-c and 4, readily available from the reaction between diethyl N,Ndichlorophosph... more The 1,4-adducts 3a-c and 4, readily available from the reaction between diethyl N,Ndichlorophosphoramidate (1) and 1,3-dienes, were found to be convenient precursors for the efiicient synthesis of the 6-chloroallylamine hydrochlorides 5a-d and N-phosphorylated allylamines 6a-c and 7. The three-step transformation of 3a-c affords the cis-3,4-dibromopyrrolidine hydrochlorides 10a-c. The preparation of the 2,5-dihydro-IH-pyrrole hydrochlorides 11 ac and trans-3,4-dibromopyrrolidine hydrochlorides 13ac is also described. The stereochemistry of the reaction is studied. Eine neue Synthese von Allylaminen und Pyrrolidinen Die 1,4-Addukte 3 a-c und 4, leicht zuganglich aus Diethyl-N,N-dichlorphosphoramidat (1) und 1,3-Dienen, bewahren sich als Ausgangsprodukte fur eine effektive Synthese von 6-Chlorallylamin-hydrochloriden 5a-d und N-Phosphorylallylaminen 6a-c und 7. Die dreistufige Umwandlung von 3a-c fuhrt zu cis-3,4-Dibrompyrrolidin-hydrochloriden 10a-c. Weiterhin wird uber die Darstellung von 2,5-Dihydro-lH-pyrroI-hydrochloriden 11 a-c und trans-3,4-Dibrompyrrolidin-hydrochloriden 13a-c berichtet. Die Stereochemie der Reaktionen wird untersucht.

Research paper thumbnail of Microwave-assisted synthesis of dialkyl ω-azidoalkylphosphonates

Synthetic Communications, 2016

Research paper thumbnail of Isothiocyanate Strategy for the Synthesis of Quaternary α‐Amino Acids Bearing a Spirocyclic Ring System

Advanced Synthesis & Catalysis, 2018

This study demonstrates that isothiocyanates derived from α‐substituted α‐amino acids are useful ... more This study demonstrates that isothiocyanates derived from α‐substituted α‐amino acids are useful building blocks in the heteroannulation reactions with electron‐deficient olefins. The developed strategy proceeds in a cascade manner and involves Michael addition followed by a cyclization via nucleophilic addition. Target, spirocyclic heterocycles bearing either a quaternary α‐amino acid moiety or α‐aminophosphonate group have been efficiently synthesized in very high yield (up to 99%) and with excellent stereocontrol. The usefulness of heterocycles obtained has been demonstrated in selected transformations.magnified image

Research paper thumbnail of Direct, Microwave‐Assisted Synthesis of Isothiocyanates

European Journal of Organic Chemistry, 2019

A microwave‐assisted desulfuration of readily available dithiocarbamates, formed in situ from pri... more A microwave‐assisted desulfuration of readily available dithiocarbamates, formed in situ from primary amines, leading to target isothiocyanates has been developed. This efficient protocol provides a rapid, environmentally benign route to aliphatic and aromatic isothiocyanates.