{"title":"Synthesis of 2‐Substituted Bicyclo[2.1.1]Hexan‐1‐ols via SmI2‐Mediated Reductive Cyclization Reactions","authors":"Chih‐Wei Hsu , Chun‐Fu Wu , Yung‐Chi Lee , Woo‐Jin Yoo","doi":"10.1002/adsc.202400891","DOIUrl":"10.1002/adsc.202400891","url":null,"abstract":"<div><div>The replacement of benzene rings with saturated bioisosteric counterparts is a key priority in drug discovery programs, and disubstituted bicyclo[2.1.1]hexanes have been recognized as flexible molecular scaffolds that could act as <em>ortho</em>‐substituted benzene bioisosteres. In this study, we outline the synthesis of a wide range of 2‐substituted bicyclo[2.1.1]hexan‐1‐ols, which have the potential to emulate <em>ortho</em>‐phenolic derivatives, via SmI<sub>2</sub>‐mediated reductive cyclization reactions. The synthetic utility of this methodology was exemplified by the preparation of several saturated analogs of pharmaceutically relevant compounds.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4747-4754"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three‐Component Synthesis of Substituted Azepines by Gold/Magnesium Orthogonal‐Relay Catalysis","authors":"Shuto Kosuge , Yoshihiro Kiraku , Kiyoshi Tsuge , Kenji Sugimoto , Yuji Matsuya","doi":"10.1002/adsc.202400940","DOIUrl":"10.1002/adsc.202400940","url":null,"abstract":"<div><div>A three‐component one‐pot synthesis of substituted azepines was realized by gold/magnesium orthogonal relay catalysis. The one‐pot synthesis involves simply mixing and heating propiolates, imines, and activated cyclopropanes to initiate a gold‐catalyzed aza‐enyne metathesis between propiolates and imines, followed by a magnesium‐catalyzed [4+3] cycloaddition reaction of the resultant 1‐azabutadienes and the cyclopropanes, yielding substituted azepines. The substituted azepines including 22 derivatives could be successfully prepared in good to excellent yield (61–95%). The reaction was also conducted on one‐gram scale.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4674-4678"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Catalytic Construction of C(sp3)−Ge Bonds: Recent Advances and Future Perspectives","authors":"Jia‐Lin Tu , Binbin Huang","doi":"10.1002/adsc.202401069","DOIUrl":"10.1002/adsc.202401069","url":null,"abstract":"<div><div>Germanium (Ge), a congener of carbon, possesses unique properties that hold extensive potential for applications across multiple domains. Recent years have seen significant progress in the development of carbon‐germanium bond formation strategies, particularly those for more challenging C(<em>sp</em><sup>3</sup>)−Ge bonds. This review systematically summarizes the recent advances in C(<em>sp</em><sup>3</sup>)−Ge bond forming methodologies, with particular emphasis on (1) the versatility of transition‐metals, including iron, nickel, copper, rhodium and palladium, as catalysts in broadening reaction scope and controlling selectivity; (2) the powerfulness of organic photocatalysis in achieving mild and selective bond formation, and (3) the sustainability of catalytic electrosynthesis in facilitating chemical oxidant‐/reductant‐ free conversions. Additionally, examples of (4) non‐catalytic strategies are also discussed. The representative scopes, as well as mechanistic proposals, of these protocols are highlighted. Through an overview on the current state of research, this review aims to offer insights into the catalytic construction of C(<em>sp</em><sup>3</sup>)−Ge bonds, and provide perspectives on future research directions to address the current challenges.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4618-4633"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Qin , Didi Liu , Bingrui Wan , Zhe Liu , Yan Ding , Haonan Zong , Yi Huang , Liang‐Hua Zou , Zengwei Lai
{"title":"Divergent Synthesis of Multisubstituted Hydroindole Derivatives via [3+2] Annulations of p‐Quinamines with Nitroalkenes","authors":"Hao Qin , Didi Liu , Bingrui Wan , Zhe Liu , Yan Ding , Haonan Zong , Yi Huang , Liang‐Hua Zou , Zengwei Lai","doi":"10.1002/adsc.202400647","DOIUrl":"10.1002/adsc.202400647","url":null,"abstract":"<div><div>The synthesis of two stereoisomers of hydroindole derivatives was achieved through [3+2] annulations of <em>p</em>‐quinamines with nitroalkenes. Catalyst‐free or in the presence of DMAP, the annulation reactions were employed to produce the target products containing four contiguous stereogenic centers. This method enables the efficient construction of multisubstituted and functionalized hydroindole derivatives from readily accessible building blocks and reagents. Furthermore, the anti‐inflammatory activity of some resulting hydroindoles was evaluated, with three derivative products showing effective inhibition of NLRP3 inflammasome activation.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4654-4660"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandro Prats Luján , Mohammad Faizan Bhat , Thangavelu Saravanan , Gerrit J. Poelarends
{"title":"Exploring the Substrate Scope and Catalytic Promiscuity of Nitroreductase‐Like Enzymes","authors":"Alejandro Prats Luján , Mohammad Faizan Bhat , Thangavelu Saravanan , Gerrit J. Poelarends","doi":"10.1002/adsc.202400220","DOIUrl":"10.1002/adsc.202400220","url":null,"abstract":"<div><div>Flavin‐dependent nitroreductases are gaining attention as biocatalysts for the synthesis of pharmaceutically active compounds and their precursors. Here, we examined a panel of nitroreductase‐like flavoenzymes for their reductase activity towards a wide variety of aromatic and aliphatic nitro compounds, nitroolefins, and α,β‐unsaturated carbonyl compounds. Several of these flavoenzymes displayed high reductase activity and achieved excellent conversion of diverse nitroarenes, nitroolefins and α,β‐unsaturated carbonyl compounds, accomplishing good product yields in semi‐preparative scale reactions (up to 97%). In addition to the catalytic promiscuity of several of these flavoenzymes, being able to perform the reduction of nitro groups (nitroreductase activity) as well as C=C groups (ene‐reductase activity), this study also revealed that some flavoenzymes exhibit high chemo‐, regio‐ and/or enantioselectivity, making them attractive enzymes for use in organic synthesis.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4679-4687"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adsc.202400220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fengkai Sun , Man Miao , Wenxue Li , Xiao‐Bing Lan , Jian‐Qiang Yu , Jian Zhang , Zhenyu An
{"title":"Direct C−C Bond Cleavage of CH3CN as a Single‐Carbon Synthon: Synthesis of Pyrrolo[1,2‐a]quinoxalines via Electrochemical Oxidation","authors":"Fengkai Sun , Man Miao , Wenxue Li , Xiao‐Bing Lan , Jian‐Qiang Yu , Jian Zhang , Zhenyu An","doi":"10.1002/adsc.202400886","DOIUrl":"10.1002/adsc.202400886","url":null,"abstract":"<div><div>A direct electrochemical redox reaction involving radical cross‐coupling cyclization for the synthesis of pyrrolo[1,2‐<em>a</em>]quinoxaline derivatives from 1‐(2‐aminophenyl)pyrroles and CH<sub>3</sub>CN has been developed, which includes the functionalization of C(<em>sp</em><sup>3</sup>)−H bonds as well as the construction of C−C and C−N bonds. Notably, the control and deuterium‐labelling experiments suggest that CH<sub>3</sub>CN in this reaction acts as both a carbon source <em>via</em> C−C cleavage and solvent. The reaction features metal‐ and oxidant‐free conditions, and various substituted pyrrolo[1,2‐<em>a</em>]quinoxaline derivatives were obtained.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4649-4653"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molybdenum‐Catalyzed Intramolecular Deoxygenative Annulation of 2‐Acylazobenzenes to Access N2,C3‐Disubstituted 2H‐Indazoles","authors":"Haoke Chu , Quanyun Liu , Mei‐Hua Shen , Hua‐Dong Xu","doi":"10.1002/adsc.202400662","DOIUrl":"10.1002/adsc.202400662","url":null,"abstract":"<div><div>A molybdenum‐catalyzed synthesis of N2,C3‐disubstituted 2<em>H</em>‐indazoles from readily available 2‐acylazobenzenes via deoxygenation of C=O and annulation has been described. The non‐noble metal catalytic system has good tolerance of functional groups, and various N2,C3‐disubstituted 2<em>H</em>‐indazoles have been constructed in 24% to 99% yield. This reaction is easy to scale‐up and has shown its applications in deriving valuable fluorescent and bioactive compounds. The plausible mechanism shows the plausible processes of molybdenum‐catalyzed deoxygenative annulation.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4661-4666"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Advances in Visible‐Light‐Mediated Synthesis of Phosphorylated Heterocycles","authors":"Fan‐lin Zeng , Zhenhua Jia , Teck‐Peng Loh","doi":"10.1002/adsc.202400819","DOIUrl":"10.1002/adsc.202400819","url":null,"abstract":"<div><div>Organophosphorus compounds, especially phosphorylated heterocycles, are gaining increasing attention in the fields of materials science, pharmaceuticals, and agrochemistry due to their excellent biological activities. Consequently, the exploration of green and efficient methods for the synthesis of phosphorylated heterocycles has garnered significant interest from organic chemists. In recent years, visible light‐induced photoredox‐catalyzed organic synthesis has made substantial progress in the field of phosphorylation reaction since its eco‐friendly and mild conditions. This review summarizes the advances of the past five years in the visible‐light‐mediated synthesis of phosphorylated heterocycles using phosphine oxides as precursors through P‐centered radical addition, cross‐coupling, and cyclization reactions.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4536-4547"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142237061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingming Zhao , Luyao Wang , Yufeng Zhou , Fenke Guo , Tao Yang , Heng‐Ying Xiong , Teng Wang , Guangwu Zhang
{"title":"Light‐Induced Iodine‐Catalyzed Dealkylative Synthesis of Enaminones","authors":"Mingming Zhao , Luyao Wang , Yufeng Zhou , Fenke Guo , Tao Yang , Heng‐Ying Xiong , Teng Wang , Guangwu Zhang","doi":"10.1002/adsc.202400631","DOIUrl":"10.1002/adsc.202400631","url":null,"abstract":"<div><div>Light mediated iodine‐catalyzed synthesis of enaminones through C−N bond cleavage has been described. In addition to substituted ynones, diverse substituted acyclic tertiary amines, and cyclic tertiary amines were also reactive under standard conditions. Selected transformations of the coupling adduct demonstrated the latent utility of this protocol. Preliminary mechanistic studies were also conducted.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4634-4638"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qingyu Wang , Lin Cong , Jiyang Guo , Jiajun Wang , Xu Han , Wenhe Zhang , Weidong Liu , Hongli Wei , Song You
{"title":"Structure‐Guided Engineering of a Short‐Chain Dehydrogenase LfSDR1 for Efficient Biosynthesis of (R)‐9‐(2‐Hydroxypropyl)adenine, the Key Intermediate of Tenofovir","authors":"Qingyu Wang , Lin Cong , Jiyang Guo , Jiajun Wang , Xu Han , Wenhe Zhang , Weidong Liu , Hongli Wei , Song You","doi":"10.1002/adsc.202400752","DOIUrl":"10.1002/adsc.202400752","url":null,"abstract":"<div><div>(<em>R</em>)‐9‐(2‐hydroxypropyl) adenine ((<em>R</em>)‐HPA) is an important intermediate for the synthesis of tenofovir and its prodrugs. Herein, structure‐guided rational design of short‐chain dehydrogenase LfSDR1 was adopted to improve the catalytic performance for enantioselective synthesis of (<em>R</em>)‐HPA at high substrate loading. The crystal structures of LfSDR1 in its apo form as well as in complex with NADPH were solved, which were used for mutagenesis studies and illustration mechanism. Three residues (G92, E141 and V186) were identified as hotspots by structural analysis, and variants V186A/G92V and V186A/G92V/E141L with remarkably improved activity were obtained. By molecular dynamics (MD) simulation of WT and variants, G92V plays a key role in enzyme‐substrate interaction in the binding pocket. Whole cells expressing the mutant LfSDR1‐V186A/G92V and glucose dehydrogenase BsGDH from <em>Bacillus subtilis</em> were used as the catalyst, and up to 200 g L<sup>−1</sup> substrate without cosolvent was completely converted to (<em>R</em>)‐HPA with 99.9% <em>ee</em> and a high space‐time yield (STY) of 800 g L<sup>−1</sup> day<sup>−1</sup>. This study improves the understanding of the catalytic mechanism of LfSDR and provides a potential biocatalytic strategy for industrial synthesis of (<em>R</em>)‐HPA.</div></div>","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":"366 22","pages":"Pages 4786-4793"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}