Pub Date : 2024-08-03DOI: 10.1016/j.tetlet.2024.155209
The efficient synthesis of sulfonated naphthols was realized by dehydroaromatization of β-tetralones with sodium sulfinates under metal-free conditions. Iodine-containing reagents played an important role in this oxidative coupling process. Sodium sulfinates served as a stable and readily available sulfur source, providing sulfones in good to excellent yields. A wide range of functional groups were well tolerated in this reaction.
{"title":"Synthesis of sulfonated naphthols via metal-free oxidative coupling of beta-tetralones and sodium sulfinates","authors":"","doi":"10.1016/j.tetlet.2024.155209","DOIUrl":"10.1016/j.tetlet.2024.155209","url":null,"abstract":"<div><p>The efficient synthesis of sulfonated naphthols was realized by dehydroaromatization of β-tetralones with sodium sulfinates under metal-free conditions. Iodine-containing reagents played an important role in this oxidative coupling process. Sodium sulfinates served as a stable and readily available sulfur source, providing sulfones in good to excellent yields. A wide range of functional groups were well tolerated in this reaction.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141936157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.tetlet.2024.155213
A straightforward and transition metal-free method for the synthesis of cyclic sulfamides via base-promoted bis-alkylation of tert-butyl (N-alkylsulfamoyl)carbamates with electron-deficient allyl bromides is described. All obtained cyclic sulfamides underwent successful removal of tert-butoxycarbonyl protecting group.
{"title":"Synthesis of cyclic sulfamides via one pot alkylation/aza-Michael cascade reaction","authors":"","doi":"10.1016/j.tetlet.2024.155213","DOIUrl":"10.1016/j.tetlet.2024.155213","url":null,"abstract":"<div><p>A straightforward and transition metal-free method for the synthesis of cyclic sulfamides via base-promoted bis-alkylation of <em>tert</em>-butyl (<em>N</em>-alkylsulfamoyl)carbamates with electron-deficient allyl bromides is described. All obtained cyclic sulfamides underwent successful removal of <em>tert</em>-butoxycarbonyl protecting group.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141936162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.tetlet.2024.155229
Haloalkynes that could be accessed from diverse precursors, are versatile in synthetic chemistry as alkynylation and/or halogenation reagents, enabling concise and divergent delivery of functional molecules in selective manners. Recently, additional reactivity and substrate scope of haloalkynes, was also developed, facilitating expedient delivery of fused heterocycles.
{"title":"Multitasking haloalkynes in synthetic chemistry","authors":"","doi":"10.1016/j.tetlet.2024.155229","DOIUrl":"10.1016/j.tetlet.2024.155229","url":null,"abstract":"<div><p>Haloalkynes that could be accessed from diverse precursors, are versatile in synthetic chemistry as alkynylation and/or halogenation reagents, enabling concise and divergent delivery of functional molecules in selective manners. Recently, additional reactivity and substrate scope of haloalkynes, was also developed, facilitating expedient delivery of fused heterocycles.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141936158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.1016/j.tetlet.2024.155228
Abaloparatide, a novel parathyroid hormone-related peptide, emerges as a leading drug for treating osteoporosis in postmenopausal women at high risk of fracture. The therapeutic agent has demonstrated efficacy in significantly enhancing bone mineral density, fortifying bone strength, and stimulating bone formation. Developing a synthetic route for Abaloparatide with high-yield and purity products is of paramount importance. This paper reported a newly developed liquid-phase synthetic method based on soluble hydrophobic support assistance for the total synthesis of Abaloparatide, which has proven to be simple, scalable, and highly effective. The optimization of reaction conditions has yielded Abaloparatide with both high yield and purity, producing satisfactory results.
{"title":"Novel synthesis of Abaloparatide: Advancing osteoporosis treatment in postmenopausal women","authors":"","doi":"10.1016/j.tetlet.2024.155228","DOIUrl":"10.1016/j.tetlet.2024.155228","url":null,"abstract":"<div><p>Abaloparatide, a novel parathyroid hormone-related peptide, emerges as a leading drug for treating osteoporosis in postmenopausal women at high risk of fracture. The therapeutic agent has demonstrated efficacy in significantly enhancing bone mineral density, fortifying bone strength, and stimulating bone formation. Developing a synthetic route for Abaloparatide with high-yield and purity products is of paramount importance. This paper reported a newly developed liquid-phase synthetic method based on soluble hydrophobic support assistance for the total synthesis of Abaloparatide, which has proven to be simple, scalable, and highly effective. The optimization of reaction conditions has yielded Abaloparatide with both high yield and purity, producing satisfactory results.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141936160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1016/j.tetlet.2024.155221
A scalable method for synthesizing the L/N ring of maitotoxin corresponding to an unnatural l-glucose derivative was developed via the MacMillan method and C-glycosylation under flow conditions. The longest linear sequence from Z-2-buten-1,4-diol was 7 steps with 10 total steps.
{"title":"Scalable synthesis of the L/N ring of maitotoxin","authors":"","doi":"10.1016/j.tetlet.2024.155221","DOIUrl":"10.1016/j.tetlet.2024.155221","url":null,"abstract":"<div><p>A scalable method for synthesizing the L/N ring of maitotoxin corresponding to an unnatural <span>l</span>-glucose derivative was developed via the MacMillan method and C-glycosylation under flow conditions. The longest linear sequence from <em>Z</em>-2-buten-1,4-diol was 7 steps with 10 total steps.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1016/j.tetlet.2024.155220
ENT-03 was predicted to be the mammalian equivalent of trodusquemine, based on knowledge of the bile acids produced in mammals, such as 7-HOCA. The individual C-25 isomers of ENT-03 were prepared and both isomers were detected in neonatal mouse brain and liver. Trodusquemine and ENT-03 have both demonstrated dramatic effects in obesity and insulin resistance. (25S)-ENT-03 was selected for development for the treatment of diabetes and obesity. In this paper the first synthesis of this putative natural product is described. Starting with a stereo-defined steroidal intermediate 2, the semi-synthesis involves three stereoselective steps: Horner-Emmons olefination, hydrogenation, and reductive amination. Asymmetric hydrogenation using a ruthenium coordinated Mandyphos ligand was found to be effective in controlling the C25-stereochemistry of both isomers. The syntheses of the ENT-03 isomers and a deuterated reference standard facilitated identification and quantification of this natural product in mouse tissues, and exploration of its therapeutic potential.
{"title":"Asymmetric synthesis of ENT-03, the predicted mammalian ortholog of the dog fish shark aminosterol trodusquemine (MSI-1436)","authors":"","doi":"10.1016/j.tetlet.2024.155220","DOIUrl":"10.1016/j.tetlet.2024.155220","url":null,"abstract":"<div><p>ENT-03 was predicted to be the mammalian equivalent of trodusquemine, based on knowledge of the bile acids produced in mammals, such as 7-HOCA. The individual C-25 isomers of ENT-03 were prepared and both isomers were detected in neonatal mouse brain and liver. Trodusquemine and ENT-03 have both demonstrated dramatic effects in obesity and insulin resistance. (25<em>S</em>)-ENT-03 was selected for development for the treatment of diabetes and obesity. In this paper the first synthesis of this putative natural product is described. Starting with a stereo-defined steroidal intermediate <strong>2</strong>, the semi-synthesis involves three stereoselective steps: Horner-Emmons olefination, hydrogenation, and reductive amination. Asymmetric hydrogenation using a ruthenium coordinated Mandyphos ligand was found to be effective in controlling the C25-stereochemistry of both isomers. The syntheses of the ENT-03 isomers and a deuterated reference standard facilitated identification and quantification of this natural product in mouse tissues, and exploration of its therapeutic potential.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141936161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1016/j.tetlet.2024.155219
A new, one-pot, two-step, and efficient method has been developed to synthesize phthalimide and its derivatives directly from phthalic acids with an iminium cation as the cyclodehydrating agent, which in turn is generated from a mixture of cyanuric chloride and N,N-dimethylformamide and amines under milder reaction conditions. This method is a simple, cost effective, and uses inexpensive and commercially available reagents and catalysts. Broad functional group tolerance of the process led to the synthesis of many phthalimides in good to excellent isolated yields (up to 98 %). This method also afforded the thalidomide drug intermediate. The plausible reaction mechanism has been also reported.
{"title":"One-pot synthesis of phthalimides from phthalic acids and amines using cyanuric chloride and N,N-dimethylformamide as a cyclodehydrating agent under milder reaction conditions","authors":"","doi":"10.1016/j.tetlet.2024.155219","DOIUrl":"10.1016/j.tetlet.2024.155219","url":null,"abstract":"<div><p>A new, one-pot, two-step, and efficient method has been developed to synthesize phthalimide and its derivatives directly from phthalic acids with an iminium cation as the cyclodehydrating agent, which in turn is generated from a mixture of cyanuric chloride and <em>N,N</em>-dimethylformamide and amines under milder reaction conditions. This method is a simple, cost effective, and uses inexpensive and commercially available reagents and catalysts. Broad functional group tolerance of the process led to the synthesis of many phthalimides in good to excellent isolated yields (up to 98 %). This method also afforded the thalidomide drug intermediate. The plausible reaction mechanism has been also reported.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1016/j.tetlet.2024.155218
A visible-light-induced radical trifluoromethylation/cyclization of unactivated alkenes for the construction of trifluoromethylated tricyclic indoles with readily accessible trifluoromethyl thianthrenium triflate has been reported. A variety of CF3-containing tricyclic indole derivatives were synthesized at room temperature without the addition of photocatalysts or additives. Mechanistic investigations indicate that the reaction probably undergo a radical pathway.
{"title":"Visible-light-induced trifluoromethylation/cyclization of unactivated alkenes: Synthesis of CF3-substituted fused tricyclic indoles","authors":"","doi":"10.1016/j.tetlet.2024.155218","DOIUrl":"10.1016/j.tetlet.2024.155218","url":null,"abstract":"<div><p>A visible-light-induced radical trifluoromethylation/cyclization of unactivated alkenes for the construction of trifluoromethylated tricyclic indoles with readily accessible trifluoromethyl thianthrenium triflate has been reported. A variety of CF<sub>3</sub>-containing tricyclic indole derivatives were synthesized at room temperature without the addition of photocatalysts or additives. Mechanistic investigations indicate that the reaction probably undergo a radical pathway.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1016/j.tetlet.2024.155203
The oxidation of diols to lactones, dialdehydes and diketones using a sub-stoichiometric quantity of an oxoammonium salt bearing the nitrate counterion is reported. In the case of linear aliphatic diols, when the diol substrate is shorter-chained, the lactone product predominates. When the chain is longer, the dialdehyde is the major product formed. A number of cyclic diols are also converted to their lactone, diketone or hydroxyketone congeners.
{"title":"Oxidation of diols using a substoichiometric quantity of an oxoammonium salt bearing the nitrate anion","authors":"","doi":"10.1016/j.tetlet.2024.155203","DOIUrl":"10.1016/j.tetlet.2024.155203","url":null,"abstract":"<div><p>The oxidation of diols to lactones, dialdehydes and diketones using a sub-stoichiometric quantity of an oxoammonium salt bearing the nitrate counterion is reported. In the case of linear aliphatic diols, when the diol substrate is shorter-chained, the lactone product predominates. When the chain is longer, the dialdehyde is the major product formed. A number of cyclic diols are also converted to their lactone, diketone or hydroxyketone congeners.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141936164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-25DOI: 10.1016/j.tetlet.2024.155215
An intermolecular highly diastereoselective oxa-Michael/Michael type stepwise cycloaddition was developed to synthesize tetrahydropyrans, using an allylic alcohol obtained from Baylis-Hillman reaction and methyl 2-(4-nitrophenyl) acrylate. These molecules were obtained in low to good yields using DBU as a base at 70 °C. This methodology provides a convenient and atom-economical approach for accessing tetrahydropyrans bearing three stereogenic centers, expanding the synthetic applicability and versatility of the oxa-Michael reactions.
{"title":"Synthesis of tetrahydropyrans via an intermolecular oxa-michael/michael stepwise cycloaddition","authors":"","doi":"10.1016/j.tetlet.2024.155215","DOIUrl":"10.1016/j.tetlet.2024.155215","url":null,"abstract":"<div><p>An intermolecular highly diastereoselective oxa-Michael/Michael type stepwise cycloaddition was developed to synthesize tetrahydropyrans, using an allylic alcohol obtained from Baylis-Hillman reaction and methyl 2-(4-nitrophenyl) acrylate. These molecules were obtained in low to good yields using DBU as a base at 70 °C. This methodology provides a convenient and atom-economical approach for accessing tetrahydropyrans bearing three stereogenic centers, expanding the synthetic applicability and versatility of the oxa-Michael reactions.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0040403924003101/pdfft?md5=8f546eef90b5029ea7ca6ccf93c67ccc&pid=1-s2.0-S0040403924003101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}