Abstract In this research, a simple and efficient strategy for the straightforward synthesis of tetracyclic dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-trione derivatives is presented by a sequential four-component reaction of arylamines, dimethyl acetylenedicarboxylate, alkylamines, and 3-formylchromones as readily available starting materials in MeOH at room temperature. The merit of this sequential enamine formation/1,2-nucleophilic addition/intramolecular aza-Michael addition is highlighted by its high energy conserving (short reaction times at room temperature), excellent yields, metal-free catalyst, easy purification (the products can be purified by simple filtration and washing with EtOH), and green and mild conditions in a one-pot reaction. Presumably, there are no previous reports for the synthesis of these classes of heterocyclic dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-trione derivatives.
{"title":"Convenient Synthesis of Functionalized Tetracyclic Dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-triones via Four-Component Reactions","authors":"Abdolali Alizadeh, Azar Rostampoor","doi":"10.1055/s-0042-1751504","DOIUrl":"https://doi.org/10.1055/s-0042-1751504","url":null,"abstract":"Abstract In this research, a simple and efficient strategy for the straightforward synthesis of tetracyclic dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-trione derivatives is presented by a sequential four-component reaction of arylamines, dimethyl acetylenedicarboxylate, alkylamines, and 3-formylchromones as readily available starting materials in MeOH at room temperature. The merit of this sequential enamine formation/1,2-nucleophilic addition/intramolecular aza-Michael addition is highlighted by its high energy conserving (short reaction times at room temperature), excellent yields, metal-free catalyst, easy purification (the products can be purified by simple filtration and washing with EtOH), and green and mild conditions in a one-pot reaction. Presumably, there are no previous reports for the synthesis of these classes of heterocyclic dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-trione derivatives.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135973751","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 : 2023-11-01Epub Date: 2023-06-13DOI: 10.1055/a-2092-9012
Andrew John Intelli, Mohan Pal, Manikandan Selvaraju, Ryan A Altman
A Pd-catalyzed decarboxylative dearomatization reaction of a heterocyclic substrate enables access to an uncommon reaction intermediate that rearomatizes in the presence of amine bases in a net C-H functionalization sequence. The dearomatized benzo[b]thiophene intermediate bears an exocyclic alkene that can be functionalized through cycloaddition and halogenation reactions to deliver complex heterocyclic products.
{"title":"Palladium-Catalyzed Dearomatization of Benzothiophenes: Isolation and Functionalization of a Discrete Dearomatized Intermediate.","authors":"Andrew John Intelli, Mohan Pal, Manikandan Selvaraju, Ryan A Altman","doi":"10.1055/a-2092-9012","DOIUrl":"10.1055/a-2092-9012","url":null,"abstract":"<p><p>A Pd-catalyzed decarboxylative dearomatization reaction of a heterocyclic substrate enables access to an uncommon reaction intermediate that rearomatizes in the presence of amine bases in a net C-H functionalization sequence. The dearomatized benzo[<i>b</i>]thiophene intermediate bears an exocyclic alkene that can be functionalized through cycloaddition and halogenation reactions to deliver complex heterocyclic products.</p>","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428306","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}
Pub Date : 2023-11-01Epub Date: 2023-06-12DOI: 10.1055/a-2085-5934
Jake M Aquilina, Myles W Smith
The Myrioneuron alkaloids are a relatively small family of plant-derived alkaloids that present an intriguing array of structural intricacy and biological properties. As such, these natural products have drawn interest from the synthetic community, resulting in creative total syntheses of several family members. This review showcases recent synthetic efforts towards these polycyclic alkaloids.
{"title":"Synthetic Studies toward the <i>Myrioneuron</i> Alkaloids.","authors":"Jake M Aquilina, Myles W Smith","doi":"10.1055/a-2085-5934","DOIUrl":"10.1055/a-2085-5934","url":null,"abstract":"<p><p>The <i>Myrioneuron</i> alkaloids are a relatively small family of plant-derived alkaloids that present an intriguing array of structural intricacy and biological properties. As such, these natural products have drawn interest from the synthetic community, resulting in creative total syntheses of several family members. This review showcases recent synthetic efforts towards these polycyclic alkaloids.</p>","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72939326","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}
Abstract A photoredox-catalyzed protocol for performing radical difunctionalization of alkenes using N-heterocyclic carbene (NHC) boranes and alkynyl bromines is described. The alkynylborylation difunctionalization reaction involves photoredox generation of boryl radical, with subsequent radical addition to the double bond followed by the capture of alkynyl bromide to form a C–C bond. This method features mild reaction conditions, remarkable chemoselectivity, broad substrate scope and good to excellent yields (up to 89%). The modification of coumarin derivatives indicates that this approach can provide a useful route for the synthesis of complex alkynylborylated products.
{"title":"Visible-Light-Enabled Radical Alkynylborylation of Activated Alkenes","authors":"Jin Xie, Congjun Zhu, Shunruo Yao","doi":"10.1055/s-0042-1751512","DOIUrl":"https://doi.org/10.1055/s-0042-1751512","url":null,"abstract":"Abstract A photoredox-catalyzed protocol for performing radical difunctionalization of alkenes using N-heterocyclic carbene (NHC) boranes and alkynyl bromines is described. The alkynylborylation difunctionalization reaction involves photoredox generation of boryl radical, with subsequent radical addition to the double bond followed by the capture of alkynyl bromide to form a C–C bond. This method features mild reaction conditions, remarkable chemoselectivity, broad substrate scope and good to excellent yields (up to 89%). The modification of coumarin derivatives indicates that this approach can provide a useful route for the synthesis of complex alkynylborylated products.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135808791","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}
A cascade, metal promoted transformations utilizing chloro allenylamide, primary amine and aryl iodide afforded piperizinones in good yields. Under the optimized conditions the cascade is performed as one-pot process allowing formation of three bonds. The synthetic route, controlled by the reaction rates of several processes involved, introduces two points of diversity and is well suited for combinatorial synthesis or related technologies.
{"title":"Synthesis of Piperazin-2-one Derivatives via Cascade Double Nucleophilic Substitution","authors":"Milos Petkovic, Dusica Kusljevic, Milos Jovanovic, Predrag Jovanovic, Gordana Tasic, Milena Simic, Vladimir Savic","doi":"10.1055/a-2201-9951","DOIUrl":"https://doi.org/10.1055/a-2201-9951","url":null,"abstract":"A cascade, metal promoted transformations utilizing chloro allenylamide, primary amine and aryl iodide afforded piperizinones in good yields. Under the optimized conditions the cascade is performed as one-pot process allowing formation of three bonds. The synthetic route, controlled by the reaction rates of several processes involved, introduces two points of diversity and is well suited for combinatorial synthesis or related technologies.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135809109","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}
Borylation of haloarene is one of the most important methodologies to synthesize borylated arenes. Generally, borylation of haloarene occurs smoothly at sterically less-hindered para- or meta-position by using a transition metal, a photoredox catalyst, or basic conditions. This study reports on ortho-specific and chemoselective borylation of ortho-iodoarene possessing carboxamide under visible-light irradiation. When a haloarene containing both C–I and C–X bonds is employed as a substrate, another C–X bond (not ortho) remains intact during the reaction. Mechanistic studies revealed that the key to success of this reaction is to generate diboron-bridged five-membered ring as a transition state, in which the diboron-bridged five-membered ring and the benzene ring in the transition state are perpendicular to each other owing to steric repulsion by the iodine atom at the ortho-position. This chemoselectivity is suitable for the synthesis of borylated building blocks.
{"title":"Carboxamide-accelerated Chemoselective Borylation of Iodoarenes under Photoirradiation","authors":"Yusei Nakashima, Michinori Sumimoto, Takashi Nishikata","doi":"10.1055/a-2202-2263","DOIUrl":"https://doi.org/10.1055/a-2202-2263","url":null,"abstract":"Borylation of haloarene is one of the most important methodologies to synthesize borylated arenes. Generally, borylation of haloarene occurs smoothly at sterically less-hindered para- or meta-position by using a transition metal, a photoredox catalyst, or basic conditions. This study reports on ortho-specific and chemoselective borylation of ortho-iodoarene possessing carboxamide under visible-light irradiation. When a haloarene containing both C–I and C–X bonds is employed as a substrate, another C–X bond (not ortho) remains intact during the reaction. Mechanistic studies revealed that the key to success of this reaction is to generate diboron-bridged five-membered ring as a transition state, in which the diboron-bridged five-membered ring and the benzene ring in the transition state are perpendicular to each other owing to steric repulsion by the iodine atom at the ortho-position. This chemoselectivity is suitable for the synthesis of borylated building blocks.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135869650","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}
Abstract 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid, known as P218, has demonstrated great potency and safety in preclinical and human studies. However, the previous synthetic methods for P218 gave low yields and required hazardous reagents and challenging procedures. In this study, we have successfully developed a decagram-scale synthetic route for P218 with practical and scalable methods for large-scale production. Furthermore, this is also a first report of a novel synthetic approach for P218-OH, a hydroxylated metabolite of P218, by modification of our discovery route. Our synthetic procedures for P218 and P218-OH are a significant advancement in drug development processes, including manufacturing processes and drug metabolism studies.
{"title":"Development of a Practical Synthetic Method for Clinical Candidate 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy} phenyl)propanoic acid (P218) and Its Hydroxylated Metabolites","authors":"Nitipol Srimongkolpithak, Onanong Vorasin, Tanawat Phumjan, Siriporn Saepua, Daniel Iwaniuk, Sumalee Kamchonwongpaisan, Yongyuth Yuthavong, Chawanee Thongpanchang","doi":"10.1055/s-0042-1751502","DOIUrl":"https://doi.org/10.1055/s-0042-1751502","url":null,"abstract":"Abstract 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid, known as P218, has demonstrated great potency and safety in preclinical and human studies. However, the previous synthetic methods for P218 gave low yields and required hazardous reagents and challenging procedures. In this study, we have successfully developed a decagram-scale synthetic route for P218 with practical and scalable methods for large-scale production. Furthermore, this is also a first report of a novel synthetic approach for P218-OH, a hydroxylated metabolite of P218, by modification of our discovery route. Our synthetic procedures for P218 and P218-OH are a significant advancement in drug development processes, including manufacturing processes and drug metabolism studies.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136019317","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}
{"title":"Linked PDF of Table of Contents","authors":"","doi":"10.1055/s-0040-1720097","DOIUrl":"https://doi.org/10.1055/s-0040-1720097","url":null,"abstract":"","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102384","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}
An efficient deprotection procedure for α,α,α-trihalogen (Cl, Br) methyl alcohols under mild reaction conditions to produce the high-performance liquid chromatography yield of series aldehydes and haloforms have been implemented. This can be applied to the de-protection of aromatic, aliphatic, and heterocyclic trihalomethyl alcohol compounds.
{"title":"Base-catalyzed Deprotection of Aldehyde: New Haloform Reaction","authors":"Gulizhabaier Abulipizi, Kadierya Abuduwaili, Shiying Tian, Mailikezhati Maihemuti, Abudu Rexit Abulikemu","doi":"10.1055/a-2201-3503","DOIUrl":"https://doi.org/10.1055/a-2201-3503","url":null,"abstract":"An efficient deprotection procedure for α,α,α-trihalogen (Cl, Br) methyl alcohols under mild reaction conditions to produce the high-performance liquid chromatography yield of series aldehydes and haloforms have been implemented. This can be applied to the de-protection of aromatic, aliphatic, and heterocyclic trihalomethyl alcohol compounds.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136104285","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}
Cheng-Lin Ding, Jun-Song Zhong, Hong Yan, Keyin Ye
Electrochemical hydrocarboxylation and deuterocarboxylation of allenes and carbon dioxide were achieved with H2O and D2O, respectively. This reaction generally affords good to excellent regioselectivity in the formation of diverse carboxylic acids.
{"title":"Electrochemical hydro- and deuterocarboxylation of allenes","authors":"Cheng-Lin Ding, Jun-Song Zhong, Hong Yan, Keyin Ye","doi":"10.1055/a-2200-5332","DOIUrl":"https://doi.org/10.1055/a-2200-5332","url":null,"abstract":"Electrochemical hydrocarboxylation and deuterocarboxylation of allenes and carbon dioxide were achieved with H2O and D2O, respectively. This reaction generally affords good to excellent regioselectivity in the formation of diverse carboxylic acids.","PeriodicalId":49451,"journal":{"name":"Synthesis-Stuttgart","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136316684","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}
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