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钯催化的碳(sp^(3))-硅键转化实现碳(sp^(3))-碳(sp^(2))偶联制备三氟丙基(杂)芳烃

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有机化学 2024年第4期44卷 1319-1326页

作者：刘君君卢涛涛马平赵庆阳邝福儿中山大学·深圳药学院(深圳) 广东深圳518107 香港中文大学化学系中国香港

使用商业可得的三烷氧基三氟丙基硅试剂,通过钯催化的碳(sp^(3))-硅键转化实现了C(sp^(3))—C(sp^(2))偶联反应.该偶联反应方法具有良好的官能团兼容性,可以有效制备一系列含多种官能团的三氟丙基(杂)芳烃.氟离子添加剂和双膦配体的脂... 详细信息

使用商业可得的三烷氧基三氟丙基硅试剂,通过钯催化的碳(sp^(3))-硅键转化实现了C(sp^(3))—C(sp^(2))偶联反应.该偶联反应方法具有良好的官能团兼容性,可以有效制备一系列含多种官能团的三氟丙基(杂)芳烃.氟离子添加剂和双膦配体的脂肪链的调节对于提高反应效率有重要的作用.

关键词：钯催化桧山偶联反应氟烷基化有机硅试剂

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu Chan Qian Guo Jasper fuk-Woo Chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui Chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China Department of Infectious Diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

Recent Expedition in Pd-Catalyzed Sonogashira Coupling and Related Processes

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Chinese Journal of Chemistry 2023年第9期41卷 1099-1118页

作者： Pui Ying Choy Kin Boon Gan fuk Yee Kwong Department of Chemistry and State Key Laboratory of Synthetic Chemistry The Chinese University of Hong KongShatinNew TerritoriesHong Kong SARChina Shenzhen Center of Novel Functional Molecules Shenzhen Municipal Key Laboratory of Chemical Synthesis of Medicinal Organic MoleculesCUHK Shenzhen Research InstituteNo.10.Second Yuexing RoadShenzhenGuangdong 518507China

Sonogashira cross-coupling protocol,typically showing the reaction between aryl/vinyl halide and terminal alkyne,has been a widely used protocol for constructing C(sp2)-C(sp)*** resulting internal alkynes are highly versatile for reaching differently function-alized alkyne-containing scaffolds or serving as valuable synthetic synthons to many other functional *** is worth noting that products originated from this coupling reaction are mostly applicable to be transformed into corresponding Z-alkene,alkane,or het-erocyclic moieties in natural product *** reaction conditions and catalyst systems are able to be tweaked in order to facil-itate the activation of steric hindered and/or electron-rich ***-catalyzed copper-free Sonogashira coupling reaction has caught increasing attention as the improved method can be more environmentally *** is more,the conditions of the cou-pling reaction can be readily amended to allow the fusion of other carbonylation or decarboxylation step in the catalytic cycle,and thus allow more complex yet versatile convergent synthesis to proceed in an operationally simple one-pot manner.

关键词： Sonogashira Alkynylation Palladium Multicomponent reactions Cross-Coupling

2000年后中国Q热的临床表现及诊疗研究进展

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中国感染与化疗杂志 2024年第2期24卷 231-239页

作者：邓超文孙林琳叶海燕陈福和邢凡凡香港大学深圳医院感染性疾病医学部感染科广东深圳518000

Q热(Q fever)是贝纳柯克斯体(Coxiella burnetii)感染引起的一种世界性分布的人畜共患病,可累及颅脑、肺脏、肝脏、心脏瓣膜、血管、骨关节等部位。Q热侵入人体网状内皮系统可引起多系统发热性急性或持续性局灶感染,急性感染表现为发热... 详细信息

Q热(Q fever)是贝纳柯克斯体(Coxiella burnetii)感染引起的一种世界性分布的人畜共患病,可累及颅脑、肺脏、肝脏、心脏瓣膜、血管、骨关节等部位。Q热侵入人体网状内皮系统可引起多系统发热性急性或持续性局灶感染,急性感染表现为发热、头痛、肺炎、肝炎等,持续性局灶感染表现为心内膜炎、血管感染、骨髓炎等。由于Q热的临床表现多样、流行病学史资料无特异性、未纳入我国法定传染性疾病、医务工作者对其诊断和治疗方面存在认识不足以及实验室检查方法未被广泛应用等原因,导致误诊和延误诊断时有发生。另一方面,国内关于Q热的研究更多聚焦在畜牧业领域或病例报告,较少有临床或研究工作者对该病进行分析总结。

关键词： Q热贝纳柯克斯体诊断治疗

Recent Developments of Genomic Research in Soybean

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Journal of Genetics and Genomics 2012年第7期39卷 317-324页

作者： Ching Chan Man-Wah Li fuk-Ling Wong Hon-Ming Lam State Key Laboratory of Agrobiolechnology and School of Life Sciences The Chinese University of Hong Kong

Soybean is an important cash crop with unique and important traits such as the high seed protein and oil contents, and the ability to perform symbiotic nitrogen fixation. A reference genome of cultivated soybeans was established in 2010, followed by whole-genome re-sequencing of wild and cultivated soybean accessions. These efforts revealed unique features of the soybean genome and helped to understand its evolution. Mapping of variations between wild and cultivated soybean genomes were perfo^aned. These genomic variations may be related to the process of domestication and human selection. Wild soybean germplasms exhibited hiigh genomic diversity and hence may be an important source of novel genes/alleles. Accumulation of genomic data will help to refine genetic maps and expedite the identification of functional genes. In this review, we summarize the major findings from the whole-genome sequencing projects and discuss the possible impacts on soybean researches and breeding programs. Some emerging areas such as transcriptomic and epigenomic studies will be introduced. In addition, we also tabulated some useful bioinformatics tools that will help the mining of the soybean genomic data.

关键词： Evolution Genome Soybean

Asymmetric hydrogenation of aromatic ketones using new chiral-bridged diphosphine/diamine-Ru(Ⅱ) complexes

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Chinese Chemical Letters 2010年第12期21卷 1403-1406页

作者： Yu Ming Cui Lai Lai Wang fuk Yee Kwong Wei Sun State Key Laboratory for Oxo Synthesis and Selective Oxidation Lanzhou Institute of Chemical Physics Chinese Academy of Sciences Lanzhou 730000 China Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis and Department of Applied Biology and Chemical technology The Hong Kong Polytechnic University Hong Kong China Graduate University of Chinese Academy of Sciences Beijing 100039 China

A series of chiral secondary alcohols were easily prepared by means of asymmetric hydrogenation of prochiral aromatic ketones using a new（（Rax）-BuP）/（R,R）-DPEN-Ru（Ⅱ） complex catalyst *** hydrogenation of 2-methylacetophenone in n-butanol （t-BuOK/Ru =45.6/1,S/C = 500,20 *** H2,20℃,48 h） afforded（S）-1-（2＇-methylphenyl）ethanol in 92%ee and〉99% conversion.

关键词： Asymmetric hydrogenation Chiral alcohols Diphosphine ligand Ruthenium complexes Diamine

Peptidic defective interfering gene nanoparticles against Omicron,Delta SARS-CoV-2 variants and influenza A virus in vivo

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3484-3493页

作者： Hanjun Zhao Chuyuan Zhang Hoiyan Lam Xinjie Meng Zheng Peng Man Lung Yeung Jasper fuk-Woo Chan Kelvin Kai-Wang To Kwok-Yung Yuen State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Department of Microbiology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina Department of Infectious Disease and Microbiology The University of Hong Kong-Shenzhen HospitalShenzhenGuangdong ProvinceChina Carol Yu Centre for Infection The University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina

Defective interfering genes(DIGs)are short viral genomes and interfere with wild-type viral ***,we demonstrate that the new designed SARS-CoV-2 DIG(CD3600)can significantly inhibit the replication of SARS-CoV-2 including Alpha,Delta,Kappa and Omicron variants in human HK-2 cells and influenza DIG(PAD4)can significantly inhibit influenza virus replication in human A549 *** dose of influenza DIGs prophylactically protects 90%mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral *** further investigate the gene delivery vector in the respiratory tract,a peptidic TAT2-P1&LAH4,which can package genes to form small spherical nanoparticles with high endosomal escape ability,is demonstrated to dramatically increase gene expression in the lung ***2-P1&LAH4,with the dual-functional TAT2-P1(gene-delivery and antiviral),can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster *** peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo,which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.

关键词： influenza vivo Delta

Enhanced replication of SARS-CoV-2 Omicron BA.2 in human forebrain and midbrain organoids

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Signal Transduction and Targeted Therapy 2022年第12期7卷 4257-4260页

作者： Yuxin Hou Chang Li Chaemin Yoon On Wah Leung Sikun You Xiaoming Cui Jasper fuk-Woo Chan Duanqing Pei Hoi Hung Cheung Hin Chu State Key Laboratory of Emerging Infectious Diseases Department of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong Kongand Centre for VirologyVaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina State Key Laboratory of Emerging Infectious Diseases Department of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong Kong Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina

Dear Editor,Coronavirus Disease 2019(COVID-19)is associated with a variety of neurological complications,including encephalopathy,encephalitis,dementia,and others.1 The pathogenic mechanism of these neurological manifestations remains incompletely understood but may be due to factors such as coagulation problem,immune-mediated response,or direct viral invasion into the central nervous system(CNS).2 We and others previously reported that ancestral SARS-CoV-2 could infect and replicate in human brain organoids.3,4 More recently,SARS-CoV-2 Omicron BA.1 emerged in late 2021 and demonstrated altered virological features including increased immunoevasion and attenuated pathogenicity comparing to SARS-CoV-2 wildtype(WT)and previous variants.5 However,the neuroinvasiveness of Omicron sublineages remain ***,we investigated the neuroinvasion and neurotoxicity of Omicron BA.1 and BA.2,and compared the findings with those of SARS-CoV-2 WT and Delta in human forebrain and midbrain *** results demonstrated that BA.2 replicated more efficiently while triggered lower levels of type I interferon response than that of SARS-CoV-2 WT,Delta,and BA.1 in both human forebrain and midbrain *** addition,BA.2 triggered substantially higher levels of apoptosis in the infected human forebrain and midbrain ***,these findings suggest that BA.2 may be different from SARS-CoV-2 WT and previous variants in its capacity in targeting and causing diseases in the human brain.

关键词： invasion finding incomplete

Artificial neural network for Evaluation of Recurrent Nasopharyngeal Carcinomas using 18-Fluoro-2-Deoxyglucose Positron Emission Tomography / Computed Tomography:Effects on Radiologists' Performance

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Artificial Neural Network for Evaluation of Recurrent Nasoph...