Nature synthesis最新文献_第9页

Publisher Correction: Cyclolignan synthesis streamlined by enantioselective hydrogenation of tetrasubstituted olefins 出版商更正：通过四取代烯烃的对映选择性氢化简化环木质素的合成

Nature synthesis Pub Date : 2024-06-27 DOI: 10.1038/s44160-024-00613-6

Wen-Xiu Xu, Zhuo Peng, Qing-Xiu Gu, Yao Zhu, Li-Han Zhao, Fucheng Leng, Hai-Hua Lu

引用次数: 0

Total synthesis of alchivemycin A using a chemoenzymatic strategy 利用化学酶法全合成茜草霉素 A

Nature synthesis Pub Date : 2024-06-27 DOI: 10.1038/s44160-024-00580-y

引用次数: 0

Microbial cell factories for cycloalkene synthesis 环烯合成微生物细胞工厂

Nature synthesis Pub Date : 2024-06-27 DOI: 10.1038/s44160-024-00584-8

Ru Jiang, Gerard Roelfes

引用次数: 0

O-to-O acyl transfer for epimerization-free peptide C-terminal salicylaldehyde ester synthesis 用于无表聚肽 C 端水杨醛酯合成的 O 到 O酰基转移

Nature synthesis Pub Date : 2024-06-27 DOI: 10.1038/s44160-024-00570-0

Wang Xia, Bing-Wen Li, Zhixiang Zhong, Jiamei Liu, Han Liu, Zhi-Xiang Yu, Xuechen Li

{"title":"O-to-O acyl transfer for epimerization-free peptide C-terminal salicylaldehyde ester synthesis","authors":"Wang Xia, Bing-Wen Li, Zhixiang Zhong, Jiamei Liu, Han Liu, Zhi-Xiang Yu, Xuechen Li","doi":"10.1038/s44160-024-00570-0","DOIUrl":"10.1038/s44160-024-00570-0","url":null,"abstract":"Peptide salicylaldehyde esters are the requisite coupling partner in Ser/Thr ligation reactions towards chemical protein synthesis. In general, it would be cost-effective and efficient to use side-chain-protected peptide acids, after Fmoc solid-phase peptide synthesis, for direct C-terminal derivatization; however, this has yet to be achieved, due to an intrinsic epimerization pathway. Here we report the development of 2-(dichloromethyl)phenol as a reagent that can directly form peptide salicylaldehyde esters in an epimerization-free manner. Mechanistic studies reveal that the 2-(dichloromethyl)phenol reagent serves as a source of highly reactive quinone methide species that can be trapped by the peptide C-terminal carboxylate to give α-chloroesters, followed by an Obenzylic-to-Ophenolic acyl transfer and chloride extrusion process. The peptide salicylaldehyde ester reaction products have been applied in the convergent total chemical synthesis of linker histone H1.2 using sequential Ser/Thr ligation reactions. C-terminal peptide salicylaldehyde ester synthesis is a challenge due to intrinsic epimerization. Now the development of epimerization-free synthesis of peptide C-terminal salicylaldehyde esters is reported. The approach uses side-chain-protected peptides, formed through solid-phase synthesis, and 2-(dichloromethyl)phenol as substrates and proceeds through an O-to-O acyl transfer process.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 8","pages":"1049-1060"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combining an artificial metathase with a fatty acid decarboxylase in a whole cell for cycloalkene synthesis 在全细胞中结合人工元酶和脂肪酸脱羧酶合成环烯烃

Nature synthesis Pub Date : 2024-06-27 DOI: 10.1038/s44160-024-00575-9

Zhi Zou, Shuke Wu, Daniel Gerngross, Boris Lozhkin, Dongping Chen, Ryo Tachibana, Thomas R. Ward

{"title":"Combining an artificial metathase with a fatty acid decarboxylase in a whole cell for cycloalkene synthesis","authors":"Zhi Zou, Shuke Wu, Daniel Gerngross, Boris Lozhkin, Dongping Chen, Ryo Tachibana, Thomas R. Ward","doi":"10.1038/s44160-024-00575-9","DOIUrl":"10.1038/s44160-024-00575-9","url":null,"abstract":"Artificial metalloenzymes (ArMs) offer powerful tools to catalyse new-to-nature reactions. Accordingly, ArMs offer great potential to complement natural enzymes in concurrent cascade reactions. For in cellulo applications, however, the abundance of thiols in the cytosol of aerobic organisms limits the use of ArMs that rely on precious-metal cofactors. To overcome this limitation, compartmentalization of ArMs either in the periplasm or on the surface of Escherichia coli has shown promise. Here we report on our efforts to combine a surface-displayed artificial metathase with UndB, an inner-membrane decarboxylase. The resulting concurrent cascade converts medium-chain dicarboxylates to cyclic alkenes. To optimize the cascade, we evolved both enzymes independently and fine-tuned their expression levels. Compared with the wild-type whole-cell enzyme cascade, the yield of the engineered strain was improved by >75-fold for the conversion of sebacic acid to cyclohexene. Combining natural and artificial metalloenzymes thus offers a promising strategy for whole-cell biocatalysis and synthetic biology to catalyse new-to-nature concurrent cascade reactions. Artificial metalloenzymes are useful catalysts in synthesis, but their use in cells is a challenge. Now, the development of an engineered whole-cell enzymatic cascade, which converts glucose-derived fatty diacids into cycloalkenes, is reported. The cascade process combines a decarboxylase with an artificial metalloenzyme that catalyses an abiotic olefin metathesis reaction.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 9","pages":"1113-1123"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A covalent molecular design enabling efficient CO2 reduction in strong acids 能在强酸中高效还原二氧化碳的共价分子设计

Nature synthesis Pub Date : 2024-06-25 DOI: 10.1038/s44160-024-00588-4

Qiang Zhang, Charles B. Musgrave III, Yun Song, Jianjun Su, Libei Huang, Le Cheng, Geng Li, Yong Liu, Yinger Xin, Qiushi Hu, Ge Ye, Hanchen Shen, Xue Wang, Ben Zhong Tang, William A. Goddard III, Ruquan Ye

{"title":"A covalent molecular design enabling efficient CO2 reduction in strong acids","authors":"Qiang Zhang, Charles B. Musgrave III, Yun Song, Jianjun Su, Libei Huang, Le Cheng, Geng Li, Yong Liu, Yinger Xin, Qiushi Hu, Ge Ye, Hanchen Shen, Xue Wang, Ben Zhong Tang, William A. Goddard III, Ruquan Ye","doi":"10.1038/s44160-024-00588-4","DOIUrl":"10.1038/s44160-024-00588-4","url":null,"abstract":"Molecular complexes are an important class of catalysts for the electrochemical carbon dioxide reduction reaction (CO2RR). However, selective CO2RR in strong acids remains challenging due to competition with the hydrogen evolution reaction. Peripheral functionalization is effective for tailoring the intrinsic activity of molecular catalysts, mostly attributed to the inductive effect or to stabilization of reaction intermediates. Here we report that peripheral functionalization of immobilized molecular complexes with quaternary ammonium groups can regulate the catalytic activity by tuning the mass distribution surrounding the active sites, enabling high-performance CO2RR in strong acids. The positively charged and hydrophobic alkylammonium groups affect the migration of water and hydronium in the double layer, while their immobilized configuration enables a stable cationic layer, inhibiting the hydrogen evolution reaction over extended potential windows. Dodecyl ammonium-functionalized cobalt phthalocyanine and tin porphyrin suppress the hydrogen Faradaic efficiency to <10% in pH ~0.5 media, while providing a single-pass conversion efficiency up to ~85%. The selectivity can be maintained at 90% even in Li+ solutions, which often exhibit poor proton shielding. Our study underscores the role of second-sphere structure for selective molecular electrochemistry. Selective electrochemical CO2 reduction (CO2RR) in strong acids remains challenging due to competition with the hydrogen evolution reaction. Now it is reported that peripheral functionalization of immobilized molecular complexes with quaternary ammonium groups can regulate the mass distribution surrounding the active sites, enabling selective CO2RR in strong acids.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 10","pages":"1231-1242"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Shattering the mirror with copper catalysis 用铜催化击碎镜子

Nature synthesis Pub Date : 2024-06-25 DOI: 10.1038/s44160-024-00589-3

Steven J. Malcolmson

引用次数: 0

Chemoenzymatic total synthesis of alchivemycin A 化学酶法全合成茜草霉素 A

Nature synthesis Pub Date : 2024-06-25 DOI: 10.1038/s44160-024-00577-7

Haoran Dong, Nianxin Guo, Dachao Hu, Benke Hong, Daohong Liao, Hong Jie Zhu, Zhang Yuan Yan, Hui Ming Ge, Xiaoguang Lei

{"title":"Chemoenzymatic total synthesis of alchivemycin A","authors":"Haoran Dong, Nianxin Guo, Dachao Hu, Benke Hong, Daohong Liao, Hong Jie Zhu, Zhang Yuan Yan, Hui Ming Ge, Xiaoguang Lei","doi":"10.1038/s44160-024-00577-7","DOIUrl":"10.1038/s44160-024-00577-7","url":null,"abstract":"Alchivemycin A belongs to a unique class of polyketide natural products isolated from plant-derived actinomycete Streptomyces. It shows potent antibacterial activity and anti-tumour activity. However, its inherent structural complexity and high oxidation state, especially the 2H-tetrahydro-4,6-dioxo-1,2-oxazine (TDO) ring system, present synthetic challenges. Here we report the total synthesis of alchivemycin A using a chemoenzymatic approach that combines de novo skeleton construction and late-stage enzymatic oxidation reactions. The convergent synthesis of the highly functionalized unnatural tetramic acid-bearing intermediate is achieved by boron-alkyl Suzuki−Miyaura cross-coupling, macrolactamization and Lacey–Dieckmann condensation reactions. Efficient enzymatic epoxidations using the redox enzymes AvmO3 and AvmO2 allow rapid access to the desired diepoxide product regio- and stereoselectively. Subsequently, a flavin adenine dinucleotide-dependent enzyme AvmO1 variant optimized via rational protein engineering, AvmO1-Y282R, was used to convert the tetramic acid ring into the TDO ring through a Baeyer–Villiger-type transformation, completing the chemoenzymatic synthesis of alchivemycin A. This work paves the way to further explore the biological functions of alchivemycin A and highlights the utility of chemoenzymatic strategies to tackle synthetic challenges in complex molecule synthesis. The asymmetric total synthesis of alchivemycin A is reported. The synthesis uses a chemoenzymatic approach that comprises de novo skeleton construction and a late-stage enzymatic oxidation cascade.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 9","pages":"1124-1133"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic kinetic asymmetric allylation, propargylation and crotylation of ketones using copper catalysis 利用铜催化酮的动态动力学不对称烯丙基化、丙炔基化和巴豆基化

Nature synthesis Pub Date : 2024-06-25 DOI: 10.1038/s44160-024-00567-9

Bo Sun, Lin-Xin Ruan, Ruyuan Zhao, Jing Zhang, Ruihan Niu, Quanjian Luo, Yurong Zhang, Lei Gao, Shi-Liang Shi

{"title":"Dynamic kinetic asymmetric allylation, propargylation and crotylation of ketones using copper catalysis","authors":"Bo Sun, Lin-Xin Ruan, Ruyuan Zhao, Jing Zhang, Ruihan Niu, Quanjian Luo, Yurong Zhang, Lei Gao, Shi-Liang Shi","doi":"10.1038/s44160-024-00567-9","DOIUrl":"10.1038/s44160-024-00567-9","url":null,"abstract":"Chiral tertiary alcohols are privileged structures found in numerous bioactive molecules and pharmaceutical agents. However, general and efficient synthetic methods for forming α,β-stereogenic tertiary alcohols bearing two or more contiguous stereocentres are rare. Here we report the development of an enantioconvergent method for the synthesis of α,β-stereogenic tertiary alcohols in a single step by allylation, propargylation or crotylation of racemic α-amino, α-(hetero)aryl and α,α-dialkyl ketones using readily available boronic ester reagents. The identification of the chiral ligand/copper catalytic system enables rapid interconversion and chiral recognition between two enantiomers of racemic ketones, allowing the dynamic kinetic resolution process to occur. The reaction features high levels of diastereoselectivity and enantioselectivity, a wide scope of heterocycle substrates and high functional group compatibility, and provides a general and efficient synthesis of a variety of complex chiral tertiary alcohols otherwise difficult to access, thereby offering a tool for the rapid modification and synthesis of drug molecules. The synthesis of α,β-stereogenic tertiary alcohols featuring multiple contiguous stereocentres is a challenge. Now, a method for the enantioconvergent copper-catalysed allylation, propargylation and crotylation of racemic ketones is reported. The process provides access to chiral tertiary alcohols bearing multiple contiguous stereocentres.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"3 9","pages":"1091-1103"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The balancing act of turning wastes into feedstocks 将废弃物转化为原料的平衡之道

Nature synthesis Pub Date : 2024-06-25 DOI: 10.1038/s44160-024-00579-5

Jennifer B. Dunn

引用次数: 0