Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04570
Julie Di Adamo,Vangelis Agouridas,Vincent Diemer,Oleg Melnyk
Guanidine hydrochloride and acetonitrile strongly inhibit native chemical ligation (NCL). These effects, considered alongside the impact of the cosolvents on the water structure, suggest that water actively participates in NCL.
{"title":"Cosolvent Effects Question the Role of Water in Native Chemical Ligation.","authors":"Julie Di Adamo,Vangelis Agouridas,Vincent Diemer,Oleg Melnyk","doi":"10.1021/acs.orglett.5c04570","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04570","url":null,"abstract":"Guanidine hydrochloride and acetonitrile strongly inhibit native chemical ligation (NCL). These effects, considered alongside the impact of the cosolvents on the water structure, suggest that water actively participates in NCL.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"130 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04564
Hao Guo,Zi Jian Jiang,Xing Yi Wang,Fang Zhou Yin,Zhang Yuan Yan,Ren Xiang Tan,Hui Ming Ge,Jing Shi
Canustatins A and B, two structurally novel polyketide metabolites, were isolated from the actinobacterium Streptomyces canus NA07887. Their structures were determined through comprehensive spectroscopic analysis, including NMR and HRESIMS, combined with the comparison of experimental and theoretical electronic circular dichroism (ECD) spectra. Canustatin A features an unprecedented 3,6-dioxabicyclo[3.1.0]hexane moiety, a structural motif rarely encountered in type I polyketides. Stable isotope labeling studies facilitated the proposal of a plausible biosynthetic pathway for these compounds. In addition, canustatin A exhibited moderate antibacterial activity against multidrug-resistant Acinetobacter baumannii ATCC AYE.
{"title":"Canustatins A and B, Two Polyketides from Streptomyces canus NA07887.","authors":"Hao Guo,Zi Jian Jiang,Xing Yi Wang,Fang Zhou Yin,Zhang Yuan Yan,Ren Xiang Tan,Hui Ming Ge,Jing Shi","doi":"10.1021/acs.orglett.5c04564","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04564","url":null,"abstract":"Canustatins A and B, two structurally novel polyketide metabolites, were isolated from the actinobacterium Streptomyces canus NA07887. Their structures were determined through comprehensive spectroscopic analysis, including NMR and HRESIMS, combined with the comparison of experimental and theoretical electronic circular dichroism (ECD) spectra. Canustatin A features an unprecedented 3,6-dioxabicyclo[3.1.0]hexane moiety, a structural motif rarely encountered in type I polyketides. Stable isotope labeling studies facilitated the proposal of a plausible biosynthetic pathway for these compounds. In addition, canustatin A exhibited moderate antibacterial activity against multidrug-resistant Acinetobacter baumannii ATCC AYE.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"7 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04717
Matthew W Reeves,Mariusz Krawiec,Scott Pennino,Jonathan T Reeves
Lateral lithiation of aryl and heteroaryl 2-methyl carboxylic acids with LDA and subsequent addition of the dianions to N-tert-butanesulfinyl ketimines gives N-sulfinyl δ-amino acids with high diastereoselectivities. One-pot sulfinyl deprotection and cyclization yield 3,3-disubstituted 3,4-dihydroisoquinolones and related heterocycles. tert-Butanesulfinyl chloride generated during the deprotection was shown to be an efficient reagent for intra- and intermolecular amide bond formation. This process gives access to δ-amino acids and 3,4-dihydroisoquinolones bearing a quaternary stereocenter that is not readily prepared by existing methods.
{"title":"δ-Quaternary Amino Acids and Dihydroisoquinolones from the Addition of Laterally Lithiated Aryl Carboxylates to N-Sulfinyl Ketimines.","authors":"Matthew W Reeves,Mariusz Krawiec,Scott Pennino,Jonathan T Reeves","doi":"10.1021/acs.orglett.5c04717","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04717","url":null,"abstract":"Lateral lithiation of aryl and heteroaryl 2-methyl carboxylic acids with LDA and subsequent addition of the dianions to N-tert-butanesulfinyl ketimines gives N-sulfinyl δ-amino acids with high diastereoselectivities. One-pot sulfinyl deprotection and cyclization yield 3,3-disubstituted 3,4-dihydroisoquinolones and related heterocycles. tert-Butanesulfinyl chloride generated during the deprotection was shown to be an efficient reagent for intra- and intermolecular amide bond formation. This process gives access to δ-amino acids and 3,4-dihydroisoquinolones bearing a quaternary stereocenter that is not readily prepared by existing methods.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A highly efficient Zn(OTf)2-catalyzed tandem isomerization/[3+2] cycloaddition cascade of 3-butynoyl pyrazole with nitrones was reported using a C1-symmetric imidazolidine-pyrroloimidazolone pyridine ligand. The resulting cycloadducts readily isomerize with silica gel or Et3N to chiral 4-isoxazolines containing an endocyclic C═C bond in up to 93% yield with 99% ee. The exocyclic olefin intermediate is effectively trapped by 1,4-benzoquinone ester under Cu(II) catalysis to afford chiral spiroketal analogues with >20:1 dr.
{"title":"Zn(II)-Catalyzed Isomerization/Asymmetric [3+2] Cycloaddition of 3-Butynoyl Pyrazole with Nitrones: Subsequent Exocyclic Olefin Isomerization and Capture.","authors":"Jia-Yi Liu,Xin-Yi Chen,Ming-Sheng Xie,Hai-Ming Guo","doi":"10.1021/acs.orglett.5c04591","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04591","url":null,"abstract":"A highly efficient Zn(OTf)2-catalyzed tandem isomerization/[3+2] cycloaddition cascade of 3-butynoyl pyrazole with nitrones was reported using a C1-symmetric imidazolidine-pyrroloimidazolone pyridine ligand. The resulting cycloadducts readily isomerize with silica gel or Et3N to chiral 4-isoxazolines containing an endocyclic C═C bond in up to 93% yield with 99% ee. The exocyclic olefin intermediate is effectively trapped by 1,4-benzoquinone ester under Cu(II) catalysis to afford chiral spiroketal analogues with >20:1 dr.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"239 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herein, we report a visible light-promoted, photocatalyst-free [2+2] photocycloaddition of coumarin-3-carboxylates with alkenes, resulting in an expeditious and efficient synthesis of cyclobutane-fused coumarins. The reaction was demonstrated on a gram scale and can also be performed under solar irradiation. The wide substrate scope, short reaction times, and high yields are highlights of this method. Preliminary mechanistic studies indicate that the reaction occurs through the involvement of an excited triplet state intermediate.
{"title":"Photochemical, Catalyst-Free [2+2] Cycloaddition of Coumarin-3-carboxylates with Alkenes.","authors":"Parashuram Sharma,Nisha Rawat,Seshadri Reddy Nasireddy,Riya Sikdar,Anand Singh","doi":"10.1021/acs.orglett.5c04113","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04113","url":null,"abstract":"Herein, we report a visible light-promoted, photocatalyst-free [2+2] photocycloaddition of coumarin-3-carboxylates with alkenes, resulting in an expeditious and efficient synthesis of cyclobutane-fused coumarins. The reaction was demonstrated on a gram scale and can also be performed under solar irradiation. The wide substrate scope, short reaction times, and high yields are highlights of this method. Preliminary mechanistic studies indicate that the reaction occurs through the involvement of an excited triplet state intermediate.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"115 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04915
Mingduo Lu,Jiaxiao Lv,Wanjun Zheng,Jie Huang,Xin Xie,Yuanhong Liu
A gold-catalyzed cascade cyclization of ene-ynamides bearing a propargyl carboxylate moiety has been developed, which involves a 1,2-migration of the alkene substituent as a key step. The method provides an efficient route for the synthesis of functionalized 2-acylquinolines, with high selectivity favoring 1,2-aryl migration over 1,2-H or -alkyl migration. In addition, the nature of the propargylic substituent has a significant effect on the reaction outcome. When an aryl substituent is present, 2-indenyl-substituted indole is formed via a cyclopropyl gold carbene intermediate, leading to cleavage of the C═C bond in the ene-ynamide substrate.
{"title":"Gold(I)-Catalyzed Cyclization of Ene-Ynamide Carboxylates Involving 1,2-Group Migration: Synthesis of Functionalized 2-Acylquinolines.","authors":"Mingduo Lu,Jiaxiao Lv,Wanjun Zheng,Jie Huang,Xin Xie,Yuanhong Liu","doi":"10.1021/acs.orglett.5c04915","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04915","url":null,"abstract":"A gold-catalyzed cascade cyclization of ene-ynamides bearing a propargyl carboxylate moiety has been developed, which involves a 1,2-migration of the alkene substituent as a key step. The method provides an efficient route for the synthesis of functionalized 2-acylquinolines, with high selectivity favoring 1,2-aryl migration over 1,2-H or -alkyl migration. In addition, the nature of the propargylic substituent has a significant effect on the reaction outcome. When an aryl substituent is present, 2-indenyl-substituted indole is formed via a cyclopropyl gold carbene intermediate, leading to cleavage of the C═C bond in the ene-ynamide substrate.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04086
Michael Desgagné, Dennis A. Kutateladze, Bradley L. Pentelute
Hexafluoroisopropanol (HFIP) is widely used as a hydrogen-bond-donor solvent. Here we demonstrate that 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB), a commonly used linker for generating C-terminal carboxylic acid peptides, cleaves from the solid support at HFIP concentrations as low as 20% in dichloromethane. The resulting yields are comparable to concentrated trifluoroacetic acid cleavage conditions. This reactivity is attributed to an added resonance structure, enabled by a p-methoxy substituent, which potentially stabilizes the benzylic carbocation intermediate during cleavage.
{"title":"Orthogonal Cleavage of the HMPB Linker from Solid Support Using HFIP","authors":"Michael Desgagné, Dennis A. Kutateladze, Bradley L. Pentelute","doi":"10.1021/acs.orglett.5c04086","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04086","url":null,"abstract":"Hexafluoroisopropanol (HFIP) is widely used as a hydrogen-bond-donor solvent. Here we demonstrate that 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB), a commonly used linker for generating C-terminal carboxylic acid peptides, cleaves from the solid support at HFIP concentrations as low as 20% in dichloromethane. The resulting yields are comparable to concentrated trifluoroacetic acid cleavage conditions. This reactivity is attributed to an added resonance structure, enabled by a <i>p</i>-methoxy substituent, which potentially stabilizes the benzylic carbocation intermediate during cleavage.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"29 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04361
Yuanyuan Li,Zhentao Zhang,Xing Chen,Tong Li,Richard R Schmidt,Peng Peng,Tianlu Li
Herein we report a general and efficient AuCl3-tBuCN cooperative catalysis system for the synthesis of 1,2-trans 2-deoxy-2-fluoro-glycosides. The reaction proceeds rapidly (15 min) under mild conditions, affording high stereoselectivity across a broad range of glycosyl donors and acceptors (40 examples, up to quantitative yield), thus enabling the streamlined chemoenzymatic assembly of fluorinated analogues of human milk oligosaccharides (HMOs). The current work provides a practical solution to long-standing challenges in the stereoselective construction of fluorinated carbohydrates.
{"title":"AuCl3-tBuCN Catalysis in 1,2-trans 2-Deoxy-2-fluoro Glycosidic Bond Formation.","authors":"Yuanyuan Li,Zhentao Zhang,Xing Chen,Tong Li,Richard R Schmidt,Peng Peng,Tianlu Li","doi":"10.1021/acs.orglett.5c04361","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04361","url":null,"abstract":"Herein we report a general and efficient AuCl3-tBuCN cooperative catalysis system for the synthesis of 1,2-trans 2-deoxy-2-fluoro-glycosides. The reaction proceeds rapidly (15 min) under mild conditions, affording high stereoselectivity across a broad range of glycosyl donors and acceptors (40 examples, up to quantitative yield), thus enabling the streamlined chemoenzymatic assembly of fluorinated analogues of human milk oligosaccharides (HMOs). The current work provides a practical solution to long-standing challenges in the stereoselective construction of fluorinated carbohydrates.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"35 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04358
Jian Chen,Jiaying Li,Xiang Li
The discovery of convenient and efficient methodologies for preparing optically active organofluorine compounds has received much attention from the synthetic community. Herein, we report an organoiodine-catalyzed desymmetric fluorolactonization of α,α-diallylcarboxylic acids in the presence of Et3N·3HF and Selectfluor, providing a straightforward access to value-added chiral α-quaternary fluorinated lactone. The reaction features moderate to good yields and broad functional group compatibility. Notably, the development of novel chiral organoiodine catalysts promotes the enantio- and diastereoselective fluorolactonization of aliphatic alkenes for the first time.
{"title":"Organoiodine-Catalyzed Desymmetric Fluorolactonization of α,α-Diallylcarboxylic Acids to Access α-Quaternary Fluorinated Lactones.","authors":"Jian Chen,Jiaying Li,Xiang Li","doi":"10.1021/acs.orglett.5c04358","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04358","url":null,"abstract":"The discovery of convenient and efficient methodologies for preparing optically active organofluorine compounds has received much attention from the synthetic community. Herein, we report an organoiodine-catalyzed desymmetric fluorolactonization of α,α-diallylcarboxylic acids in the presence of Et3N·3HF and Selectfluor, providing a straightforward access to value-added chiral α-quaternary fluorinated lactone. The reaction features moderate to good yields and broad functional group compatibility. Notably, the development of novel chiral organoiodine catalysts promotes the enantio- and diastereoselective fluorolactonization of aliphatic alkenes for the first time.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"11 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04073
Olesya Zvereva,Fedor S Kliuev,Natalia Lebedeva,Evgeniya Podyacheva,Evgenii Gutsul,Oleg I Afanasyev,Denis Chusov
We report a catalytic method for reductive amination using sodium hypophosphite as a cheap, bulk-grade available, and environmentally friendly reductant. The use of CpRu(PPh3)2Cl allowed the reaction to proceed under mild conditions, affording products in preparative yields. The method demonstrated great tolerance for a wide range of functional groups. A set of mechanistic trials resulted in one of the possible catalytic species, the Ru-hydride complex, being identified by NMR. A plausible mechanism of the process was proposed.
{"title":"Sodium Hypophosphite Assisted Ruthenium Catalyzed Reductive Amination under Mild Conditions.","authors":"Olesya Zvereva,Fedor S Kliuev,Natalia Lebedeva,Evgeniya Podyacheva,Evgenii Gutsul,Oleg I Afanasyev,Denis Chusov","doi":"10.1021/acs.orglett.5c04073","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04073","url":null,"abstract":"We report a catalytic method for reductive amination using sodium hypophosphite as a cheap, bulk-grade available, and environmentally friendly reductant. The use of CpRu(PPh3)2Cl allowed the reaction to proceed under mild conditions, affording products in preparative yields. The method demonstrated great tolerance for a wide range of functional groups. A set of mechanistic trials resulted in one of the possible catalytic species, the Ru-hydride complex, being identified by NMR. A plausible mechanism of the process was proposed.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"127 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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