Pub Date : 2025-03-26DOI: 10.1016/j.tet.2025.134624
Ke-Ming Li , Wei-Fen Li , Madhu Babu Sura , Guangyi Yang , Yong-Xian Cheng
Five previously undescribed monoterpenoids, including two 1,2-dimethyl cantharimide-type derivatives (1 and 2), one 1-hydroxymethyl-2-methyl cantharimide-type derivative (3), and two 1-methyl cantharimide-type derivatives (4 and 5), were isolated from the whole bodies of Mylabris cichorii L. Their structures, including absolute configurations, were identified using 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) calculations. Considering the role of cantharidin derivatives in anti-neuroinflammation, all the compounds were evaluated for their neuroinflammatory activities. Results showed that compound 2 ameliorated LPS-induced neuroinflammation and reduced oxidative stress by targeting mitochondria, thereby decreasing reactive oxygen species (ROS) and pro-inflammatory cytokines. This suggests that compound 2 may be useful in treating neuroinflammatory diseases.
{"title":"Five new cantharidin derivatives from the insect Mylabris cichorii and their potential for the treatment of neuroinflammatory diseases","authors":"Ke-Ming Li , Wei-Fen Li , Madhu Babu Sura , Guangyi Yang , Yong-Xian Cheng","doi":"10.1016/j.tet.2025.134624","DOIUrl":"10.1016/j.tet.2025.134624","url":null,"abstract":"<div><div>Five previously undescribed monoterpenoids, including two 1,2-dimethyl cantharimide-type derivatives (<strong>1</strong> and <strong>2</strong>), one 1-hydroxymethyl-2-methyl cantharimide-type derivative (<strong>3</strong>), and two 1-methyl cantharimide-type derivatives (<strong>4</strong> and <strong>5</strong>), were isolated from the whole bodies of <em>Mylabris cichorii</em> L. Their structures, including absolute configurations, were identified using 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) calculations. Considering the role of cantharidin derivatives in anti-neuroinflammation, all the compounds were evaluated for their neuroinflammatory activities. Results showed that compound <strong>2</strong> ameliorated LPS-induced neuroinflammation and reduced oxidative stress by targeting mitochondria, thereby decreasing reactive oxygen species (ROS) and pro-inflammatory cytokines. This suggests that compound <strong>2</strong> may be useful in treating neuroinflammatory diseases.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134624"},"PeriodicalIF":2.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-26DOI: 10.1016/j.tet.2025.134623
Jiangtao He, Abu Rustum
During the stability test of a liquid finished drug product (topical liquid transdermal formulation), an unexpected unknown peak was observed in the High Performance Liquid Chromatography (HPLC) chromatogram. This finished drug product is used to control mixed infestations of ectoparasites, nematodes, and cestodes in cats. This topical liquid drug product contains three active pharmaceutical ingredients (APIs), esafoxolaner, eprinomectin, and praziquantel. The identity of any new unknown peak (above certain threshold) in any given finished product batch must be established to ensure that the unknown peak is correctly estimated against the parent compound (API). As there are three APIs in this product, an incorrect assignment of the origin and identity of any given impurity will cause either overestimation or underestimation of the impurity, including misleading information on safety. Therefore, the chemical structure and the correct origin/source(s) of this unknown peak need to be determined. Although High Resolution Mass Spectrometry (HRMS) provides valuable information for determining the structure of the impurity associated with this peak, its structure cannot be fully established by HRMS data alone. Hence, this impurity peak was isolated and purified from aged finished drug product stability samples by semi-prep HPLC. Its chemical structure was fully elucidated through Nuclear Magnetic Resonance (NMR) (1H, 13C, and 2D). The results revealed that the impurity was formed through a cross-reaction between a praziquantel degradant and butylated hydroxytoluene (BHT), which is used as an antioxidant in the finished drug product. The experimental details and full structure elucidation data and related information of this unexpected new degradation product peak is reported in this paper. The mechanism of formation of this impurity is proposed based on its positively identified chemical structure. Based on an extensive literature search, it can be concluded that this is the first known report on the definitive identification of the chemical structure and formation mechanisms of this impurity.
{"title":"Isolation and chemical structure elucidation of a new praziquantel degradant and BHT crosslinked impurity in a liquid finished drug product","authors":"Jiangtao He, Abu Rustum","doi":"10.1016/j.tet.2025.134623","DOIUrl":"10.1016/j.tet.2025.134623","url":null,"abstract":"<div><div>During the stability test of a liquid finished drug product (topical liquid transdermal formulation), an unexpected unknown peak was observed in the High Performance Liquid Chromatography (HPLC) chromatogram. This finished drug product is used to control mixed infestations of ectoparasites, nematodes, and cestodes in cats. This topical liquid drug product contains three active pharmaceutical ingredients (APIs), esafoxolaner, eprinomectin, and praziquantel. The identity of any new unknown peak (above certain threshold) in any given finished product batch must be established to ensure that the unknown peak is correctly estimated against the parent compound (API). As there are three APIs in this product, an incorrect assignment of the origin and identity of any given impurity will cause either overestimation or underestimation of the impurity, including misleading information on safety. Therefore, the chemical structure and the correct origin/source(s) of this unknown peak need to be determined. Although High Resolution Mass Spectrometry (HRMS) provides valuable information for determining the structure of the impurity associated with this peak, its structure cannot be fully established by HRMS data alone. Hence, this impurity peak was isolated and purified from aged finished drug product stability samples by semi-prep HPLC. Its chemical structure was fully elucidated through Nuclear Magnetic Resonance (NMR) (<sup>1</sup>H, <sup>13</sup>C, and 2D). The results revealed that the impurity was formed through a cross-reaction between a praziquantel degradant and butylated hydroxytoluene (BHT), which is used as an antioxidant in the finished drug product. The experimental details and full structure elucidation data and related information of this unexpected new degradation product peak is reported in this paper. The mechanism of formation of this impurity is proposed based on its positively identified chemical structure. Based on an extensive literature search, it can be concluded that this is the first known report on the definitive identification of the chemical structure and formation mechanisms of this impurity.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134623"},"PeriodicalIF":2.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.tet.2025.134616
Alberto Insuasty , Serena Carrara , Doan Vu , Joel José Montalvo-Acosta , Alejandro Ortíz , Conor Hogan , Christopher R. McNeill , Steven J. Langford
In this work we explore the use of the method of oxidation and heterocyclization of naphthalene diimides (NDIs) to obtain five novel isoquinoline diimide derivatives (IQDI 3–7) as new small molecule acceptors. These derivatives comprise a main core based on triphenylamine (TPA) as electron-donor linked to an isoquinoline diimide moiety as a new electron-acceptor (IQDI 3). The effect on the electronic properties of a further functionalization on TPA achieving A-D-A architectures with additional electron acceptors moieties such as carbonyl group (IQDI 4), 3-methylrhodanine (IQDI 5), 1,3-indandione (IQDI 6) and malononitrile (IQDI 7) was studied. Their electrochemical and optoelectronic properties as well as their performance in photovoltaic devices using J52 as electron-donor polymer were studied being IQDI 6 the compound that showed the best PCE % value.
{"title":"Synthesis and evaluation of new isoquinoline diimide derivatives as small molecule acceptors for organic solar cells","authors":"Alberto Insuasty , Serena Carrara , Doan Vu , Joel José Montalvo-Acosta , Alejandro Ortíz , Conor Hogan , Christopher R. McNeill , Steven J. Langford","doi":"10.1016/j.tet.2025.134616","DOIUrl":"10.1016/j.tet.2025.134616","url":null,"abstract":"<div><div>In this work we explore the use of the method of oxidation and heterocyclization of naphthalene diimides (NDIs) to obtain five novel isoquinoline diimide derivatives (<strong>IQDI 3</strong>–<strong>7</strong>) as new small molecule acceptors. These derivatives comprise a main core based on triphenylamine (TPA) as electron-donor linked to an isoquinoline diimide moiety as a new electron-acceptor (<strong>IQDI 3</strong>). The effect on the electronic properties of a further functionalization on TPA achieving A-D-A architectures with additional electron acceptors moieties such as carbonyl group (<strong>IQDI 4</strong>), 3-methylrhodanine (<strong>IQDI 5</strong>), 1,3-indandione (<strong>IQDI 6</strong>) and malononitrile (<strong>IQDI 7</strong>) was studied. Their electrochemical and optoelectronic properties as well as their performance in photovoltaic devices using <strong>J52</strong> as electron-donor polymer were studied being <strong>IQDI 6</strong> the compound that showed the best PCE % value.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134616"},"PeriodicalIF":2.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.tet.2025.134619
C. Elizabeth Adams, Steven D. Townsend
Yaretol is a polycyclic norditerpene constituting a structurally distinct class of terpene natural products isolated from Azorella madreporica which, to date, has not been accessed via total synthesis. Herein, we report our synthetic efforts toward a key intramolecular Diels-Alder furan (IMDAF) cycloaddition to construct the carbon framework. We discuss our efforts toward the cycloaddition wherein undesired aromatization and unanticipated rearrangement of the cycloadduct are observed.
{"title":"Studies toward the synthesis of yaretol: an unexpected rearrangement en route to the tricyclic core","authors":"C. Elizabeth Adams, Steven D. Townsend","doi":"10.1016/j.tet.2025.134619","DOIUrl":"10.1016/j.tet.2025.134619","url":null,"abstract":"<div><div>Yaretol is a polycyclic norditerpene constituting a structurally distinct class of terpene natural products isolated from <em>Azorella madreporica</em> which, to date, has not been accessed via total synthesis. Herein, we report our synthetic efforts toward a key intramolecular Diels-Alder furan (IMDAF) cycloaddition to construct the carbon framework. We discuss our efforts toward the cycloaddition wherein undesired aromatization and unanticipated rearrangement of the cycloadduct are observed.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134619"},"PeriodicalIF":2.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.tet.2025.134618
Xiao-Wei Cong , Yu Peng
Ceforalide B is a representative molecule with a complex rigid skeleton composed of ABCDE pentacycle in the benzenoid cephalotane-type norditerpenoids family, which contains five contiguous stereogenic centers involving an all-carbon quaternary center. An advanced intermediate with the ACDE rings has been synthesized from 3,5-dimethylphenol. While the organocatalyzed diastereoselective intramolecular Michael addition and aldol condensation reaction successfully secure the rapid construction of the ACD tricyclic framework, the Yb(OTf)3-catalyzed stereoselective hydroxymethylation, 1,2-addition, followed by a PDC-mediated oxidative rearrangement reaction also play important roles in elaborating this tricyclic core. Additionally, the late-stage C1 epimerization and the construction of bridging lactone for E ring by a Mitsunobu reaction were further used to build the tetracyclic carbon skeleton.
{"title":"Synthesis of the ACDE tetracyclic skeleton in ceforalide B","authors":"Xiao-Wei Cong , Yu Peng","doi":"10.1016/j.tet.2025.134618","DOIUrl":"10.1016/j.tet.2025.134618","url":null,"abstract":"<div><div>Ceforalide B is a representative molecule with a complex rigid skeleton composed of ABCDE pentacycle in the benzenoid cephalotane-type norditerpenoids family, which contains five contiguous stereogenic centers involving an all-carbon quaternary center. An advanced intermediate with the ACDE rings has been synthesized from 3,5-dimethylphenol. While the organocatalyzed diastereoselective intramolecular Michael addition and aldol condensation reaction successfully secure the rapid construction of the ACD tricyclic framework, the Yb(OTf)<sub>3</sub>-catalyzed stereoselective hydroxymethylation, 1,2-addition, followed by a PDC-mediated oxidative rearrangement reaction also play important roles in elaborating this tricyclic core. Additionally, the late-stage C1 epimerization and the construction of bridging lactone for E ring by a Mitsunobu reaction were further used to build the tetracyclic carbon skeleton.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"179 ","pages":"Article 134618"},"PeriodicalIF":2.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.tet.2025.134620
Xiuyuan Duan, Guojun Zheng
The most well-known reaction between diazo compounds and alkenes is cyclopropanation, which proceeds via a metal carbene or free carbene intermediate. In recent years, significant progress has been made in visible-light photocatalysis of diazo compounds to generate radicals and subsequent functionalization reactions. In this work, the photocatalytic intramolecular radical cyclization of aryl diazo compounds has been developed, resulting in the formation of benzoxepine derivatives with moderate yields. Mechanistic experiments support the formation of a carbon-centered radical from the diazoalkane via a proton-coupled electron transfer (PCET) process. This reaction, which is easy to perform, allowing the rapid conversion of aryl diazo compounds into benzoxepine derivatives under mild conditions.
{"title":"Visible-light-driven synthesis of benzoxepine derivatives from aromatic diazo compounds","authors":"Xiuyuan Duan, Guojun Zheng","doi":"10.1016/j.tet.2025.134620","DOIUrl":"10.1016/j.tet.2025.134620","url":null,"abstract":"<div><div>The most well-known reaction between diazo compounds and alkenes is cyclopropanation, which proceeds via a metal carbene or free carbene intermediate. In recent years, significant progress has been made in visible-light photocatalysis of diazo compounds to generate radicals and subsequent functionalization reactions. In this work, the photocatalytic intramolecular radical cyclization of aryl diazo compounds has been developed, resulting in the formation of benzoxepine derivatives with moderate yields. Mechanistic experiments support the formation of a carbon-centered radical from the diazoalkane via a proton-coupled electron transfer (PCET) process. This reaction, which is easy to perform, allowing the rapid conversion of aryl diazo compounds into benzoxepine derivatives under mild conditions.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"179 ","pages":"Article 134620"},"PeriodicalIF":2.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.tet.2025.134613
B.V. Subba Reddy
{"title":"Editorial for the special issue commemorating the 90th birthday of Dr A V Rama Rao","authors":"B.V. Subba Reddy","doi":"10.1016/j.tet.2025.134613","DOIUrl":"10.1016/j.tet.2025.134613","url":null,"abstract":"","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134613"},"PeriodicalIF":2.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-22DOI: 10.1016/j.tet.2025.134607
Zhong-Lian Ma , Zhi-Pu Yu , Ling Lv , Zhi-Qing Liu , Chang-Yun Wang , Guang-Shan Yao
An oxidized 5/5/6 tricyclic sesquiterpene with a new 6-isopropyl-1,2,9-trimethyl-spiro [4.4]nonane carbon skeleton, metarhizane A (1), was isolated from a rare marine derived fungus Metarhizium sp. P2100. Its structure and the absolute configurations were assigned by interpretation of a combination of spectroscopic data and X-ray diffraction. This is the first example with a spiro [4,4] nonane core among the sesquiterpene skeletons. A plausible biosynthetic pathway for metarhizane A (1) initiated from farnesyl diphosphate (FPP) was predicted and discussed. The above results suggested that this marine-derived fungus has the potential to produce novel skeletons.
{"title":"A new sesquiterpene with a specialized [4,4] bicyclononane skeleton from the marine-derived fungus Metarhizium sp. P2100","authors":"Zhong-Lian Ma , Zhi-Pu Yu , Ling Lv , Zhi-Qing Liu , Chang-Yun Wang , Guang-Shan Yao","doi":"10.1016/j.tet.2025.134607","DOIUrl":"10.1016/j.tet.2025.134607","url":null,"abstract":"<div><div>An oxidized 5/5/6 tricyclic sesquiterpene with a new 6-isopropyl-1,2,9-trimethyl-spiro [4.4]nonane carbon skeleton, metarhizane A (<strong>1</strong>), was isolated from a rare marine derived fungus <em>Metarhizium</em> sp. P2100. Its structure and the absolute configurations were assigned by interpretation of a combination of spectroscopic data and X-ray diffraction. This is the first example with a spiro [4,4] nonane core among the sesquiterpene skeletons. A plausible biosynthetic pathway for metarhizane A (<strong>1</strong>) initiated from farnesyl diphosphate (FPP) was predicted and discussed. The above results suggested that this marine-derived fungus has the potential to produce novel skeletons.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134607"},"PeriodicalIF":2.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-22DOI: 10.1016/j.tet.2025.134611
Hiroto Kimura , Takuya Hashimoto
Oxazolidinones are used as drug motifs and chiral auxiliaries in synthetic organic chemistry. We report herein an imidazole-mediated deprotection of N-(fluorosulfonyl)oxazolidinones to N-unprotected oxazolidinones. Given the accessibility of enantioenriched N-(fluorosulfonyl)oxazolidinones via our organoiodine-catalyzed enantioselective oxyamination of alkenes, this procedure offers a new and robust method to generate valuable oxazolidinone scaffolds.
{"title":"Imidazole-mediated defluorosulfonylation of N-(fluorosulfonyl)oxazolidinones accessed by an organoiodine(I/III)-catalyzed oxyamination","authors":"Hiroto Kimura , Takuya Hashimoto","doi":"10.1016/j.tet.2025.134611","DOIUrl":"10.1016/j.tet.2025.134611","url":null,"abstract":"<div><div>Oxazolidinones are used as drug motifs and chiral auxiliaries in synthetic organic chemistry. We report herein an imidazole-mediated deprotection of N-(fluorosulfonyl)oxazolidinones to N-unprotected oxazolidinones. Given the accessibility of enantioenriched N-(fluorosulfonyl)oxazolidinones via our organoiodine-catalyzed enantioselective oxyamination of alkenes, this procedure offers a new and robust method to generate valuable oxazolidinone scaffolds.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134611"},"PeriodicalIF":2.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A synthetic route for the novel nucleosides 4′-methylsulfanyluridine (20a) and –cytidine (26) has been developed. This route consists of two steps; 1) preparation of 4′-O-benzoyloxy-xylofuranosylnucleoside 13 through electrophilic iodo-benzoyloxylation to 4′,5′-unsaturated uracil nulesoside 9 and replacement of the iodo-substituent at the 5′-position with the benzoyloxy group, 2) nucleophilic substitution of 13 with Me3SiSMe leading to the 4′-α-methylsulfanylnucleoside 14a stereoselectively. The possible reaction mechanism of the 5′-deoxy-5′-iodonucleosides 10a and 10b with AgOBz is discussed. The transformation of the xylofuranosyl moiety of 14a into the ribonucleoside 20a was performed on the basis of the ring-opening of the O2,2′-anhydronucleoside 24 with benzoate ion. In this study, 4′-methylsulfanylcytidine 26 was also synthesized.
{"title":"Stereoselective synthesis of novel 4′-methylsulfanyl-pyrimidine ribonucleosides by means of nucleophilic substitution of the 4′-benzoyloxy leaving group","authors":"Kazuhiro Haraguchi , Yasuaki Kimura , Hiroshi Abe , Hiroki Kumamoto , Hiromichi Tanaka","doi":"10.1016/j.tet.2025.134581","DOIUrl":"10.1016/j.tet.2025.134581","url":null,"abstract":"<div><div>A synthetic route for the novel nucleosides 4′-methylsulfanyluridine (<strong>20a</strong>) and –cytidine (<strong>26</strong>) has been developed. This route consists of two steps; 1) preparation of 4′-<em>O</em>-benzoyloxy-xylofuranosylnucleoside <strong>13</strong> through electrophilic iodo-benzoyloxylation to 4′,5′-unsaturated uracil nulesoside <strong>9</strong> and replacement of the iodo-substituent at the 5′-position with the benzoyloxy group, 2) nucleophilic substitution of <strong>13</strong> with Me<sub>3</sub>SiSMe leading to the 4′-α-methylsulfanylnucleoside <strong>14a</strong> stereoselectively. The possible reaction mechanism of the 5′-deoxy-5′-iodonucleosides <strong>10a</strong> and <strong>10b</strong> with AgOBz is discussed. The transformation of the xylofuranosyl moiety of <strong>14a</strong> into the ribonucleoside <strong>20a</strong> was performed on the basis of the ring-opening of the <em>O</em><sup>2</sup>,2′-anhydronucleoside <strong>24</strong> with benzoate ion. In this study, 4′-methylsulfanylcytidine <strong>26</strong> was also synthesized.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"179 ","pages":"Article 134581"},"PeriodicalIF":2.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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