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Papers by Zisis Peitsinis

Journal of the American Chemical Society

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a w... more Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ¹²-prostaglandin J₂ (Δ¹²-PGJ₂) and Δ¹²-prostaglandin J₃ (Δ¹²-PGJ₃), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein, we report a short olefin-metathesis-based total synthesis of Δ¹²-PGJ₂ and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric, and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure–activity relationships and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecules

The total synthesis of cytotoxic meroditerpenoid naphthoquinone derivative chabrolonaphthoquinone... more The total synthesis of cytotoxic meroditerpenoid naphthoquinone derivative chabrolonaphthoquinone B (1) in an enantiospecific manner is divulged using a chiral pool approach. The key step of our synthetic route is a modified Julia olefination between a sulfone-bearing aliphatic fragment and a Diels-Alder-derived aromatic aldehyde, leading to the stereoselective construction of the E-trisubstituted double bond.

Synlett, 2021

The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and rel... more The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, MPro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.

Beilstein Journal of Organic Chemistry, 2020

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corres... more A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction ...

The Journal of Organic Chemistry, 2019

W e became aware after publication of our original manuscript that the structures of compounds 5a... more W e became aware after publication of our original manuscript that the structures of compounds 5a−d in Figure 2, and of compounds 5a−d, 6a−d, and 7a−d in Schemes 1−4, respectively, have been wrongly depicted. This error also affected the Abstract graphic/Table of Contents graphic, the Supporting Information, and the names for compounds 5a−d within the Experimental Section. Last, the X substituent has not been properly described for compounds 14 (Schemes 2 and 4), 19 (Scheme 2), and 31 (Scheme 4). Importantly, none of the aforementioned errors has any influence on the drawn conclusions. The corrected structures and compound names are given below. We apologize for possible confusion caused by these errors. The Abstract/Table of Contents graphic and affected graphics for Figure 2 and Schemes 1−4 are shown below.

The Journal of Organic Chemistry, 2018

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a w... more Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ 12-prostaglandin J2 (Δ 12-PGJ2) and Δ 12prostaglandin J3 (Δ 12-PGJ3), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein we report a short olefinmetathesis based total synthesis of Δ 12-PGJ2 and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure-activity relationships (SARs) and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecule.

ChemMedChem, Jan 17, 2017

The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by dire... more The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a d-ribose-derived chiron. Naturally occurring trachycladines A and B and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung, and cervical cancer). Parent trachycladine A and two analogues (the diacetate of the 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) resulted in a significant decrease in cell viability, with the latter exhibiting a stronger effect. The same compounds enhanced the cytotoxic effect of docetaxel in lung cancer cell lines, whereas additional experiments revealed that their mode of action relies on mitotic catastrophe rather than DNA damage. Moreover, their activity as autophagic flux blockers was postulated.

European Journal of Organic Chemistry, 2014

The synthesis of marine nucleosides trachycladines A and B and two nucleoside analogues was accom... more The synthesis of marine nucleosides trachycladines A and B and two nucleoside analogues was accomplished following a versatile and high‐yielding scheme starting from D‐ribose. The key step involved a regio‐ and stereoselective direct Vorbrüggen glycosylation reaction between the appropriate nucleobase and a common intermediate, 2‐C‐methyl‐D‐5‐deoxyribofuranose triacetate.

Journal of the American Chemical Society

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a w... more Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ¹²-prostaglandin J₂ (Δ¹²-PGJ₂) and Δ¹²-prostaglandin J₃ (Δ¹²-PGJ₃), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein, we report a short olefin-metathesis-based total synthesis of Δ¹²-PGJ₂ and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric, and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure–activity relationships and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecules

The total synthesis of cytotoxic meroditerpenoid naphthoquinone derivative chabrolonaphthoquinone... more The total synthesis of cytotoxic meroditerpenoid naphthoquinone derivative chabrolonaphthoquinone B (1) in an enantiospecific manner is divulged using a chiral pool approach. The key step of our synthetic route is a modified Julia olefination between a sulfone-bearing aliphatic fragment and a Diels-Alder-derived aromatic aldehyde, leading to the stereoselective construction of the E-trisubstituted double bond.

Synlett, 2021

The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and rel... more The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, MPro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.

Beilstein Journal of Organic Chemistry, 2020

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corres... more A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction ...

The Journal of Organic Chemistry, 2019

W e became aware after publication of our original manuscript that the structures of compounds 5a... more W e became aware after publication of our original manuscript that the structures of compounds 5a−d in Figure 2, and of compounds 5a−d, 6a−d, and 7a−d in Schemes 1−4, respectively, have been wrongly depicted. This error also affected the Abstract graphic/Table of Contents graphic, the Supporting Information, and the names for compounds 5a−d within the Experimental Section. Last, the X substituent has not been properly described for compounds 14 (Schemes 2 and 4), 19 (Scheme 2), and 31 (Scheme 4). Importantly, none of the aforementioned errors has any influence on the drawn conclusions. The corrected structures and compound names are given below. We apologize for possible confusion caused by these errors. The Abstract/Table of Contents graphic and affected graphics for Figure 2 and Schemes 1−4 are shown below.

The Journal of Organic Chemistry, 2018

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a w... more Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ 12-prostaglandin J2 (Δ 12-PGJ2) and Δ 12prostaglandin J3 (Δ 12-PGJ3), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein we report a short olefinmetathesis based total synthesis of Δ 12-PGJ2 and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure-activity relationships (SARs) and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecule.

ChemMedChem, Jan 17, 2017

The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by dire... more The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a d-ribose-derived chiron. Naturally occurring trachycladines A and B and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung, and cervical cancer). Parent trachycladine A and two analogues (the diacetate of the 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) resulted in a significant decrease in cell viability, with the latter exhibiting a stronger effect. The same compounds enhanced the cytotoxic effect of docetaxel in lung cancer cell lines, whereas additional experiments revealed that their mode of action relies on mitotic catastrophe rather than DNA damage. Moreover, their activity as autophagic flux blockers was postulated.

European Journal of Organic Chemistry, 2014

The synthesis of marine nucleosides trachycladines A and B and two nucleoside analogues was accom... more The synthesis of marine nucleosides trachycladines A and B and two nucleoside analogues was accomplished following a versatile and high‐yielding scheme starting from D‐ribose. The key step involved a regio‐ and stereoselective direct Vorbrüggen glycosylation reaction between the appropriate nucleobase and a common intermediate, 2‐C‐methyl‐D‐5‐deoxyribofuranose triacetate.