https://www.x-mol.com/groups/qixiangbing/people

http://qigroup.nibs.ac.cn/people/

https://www.x-mol.com/groups/qixiangbing/people

http://qigroup.nibs.ac.cn/research/

目前实验室研究方向主要有具有生物活性的有机小分子药物开发, 化学小分子库的构建和高通量筛选，天然小分子全合成和生物仿生合成，同时开发新型化学小分子探针用于鉴定药物新靶点并通过探索化学生物学新策略研究小分子与靶点的相互作用关系调控重要的生物学机理。基于自然丰富的原材料的新颖有机合成方法学开发，基于高生物活性的天然产物的全合成和药物开发，基于高通量化合物筛选的药物化学和化学生物学等。结合构效关系优化苗头化合物小分子结构成特异性高活性分子探针和先导化合物，利用化学生物学手段探索未知的分子生物学机理并鉴定全新的生物医药靶点，进而开发尚未满足临床需求(Unmet Medical Needs)的原始创新（First-in-Class）药物,如抑制乙肝病毒感染，生物钟调节，小分子诱导蛋白降解等。

项目:

1.国家重点基础研究计划 (973计划):“病原体感染相关新蛋白靶点药物研发”课题（2014CB849603）

2.科技部“重点领域创新团队”计划-2019

3.国家自然科学基金：“基于呋喃选择性氧化重排和吲哚亲核加成串联反应的吲哚类生物碱的全合成”（21971018）

4.北京市青年拔尖人才支持计划

5.北京“高创计划”百千万工程领军人才

6.北京市海外高层次人才

http://qigroup.nibs.ac.cn/research/

目前实验室研究方向主要有具有生物活性的有机小分子药物开发, 化学小分子库的构建和高通量筛选，天然小分子全合成和生物仿生合成，同时开发新型化学小分子探针用于鉴定药物新靶点并通过探索化学生物学新策略研究小分子与靶点的相互作用关系调控重要的生物学机理。基于自然丰富的原材料的新颖有机合成方法学开发，基于高生物活性的天然产物的全合成和药物开发，基于高通量化合物筛选的药物化学和化学生物学等。结合构效关系优化苗头化合物小分子结构成特异性高活性分子探针和先导化合物，利用化学生物学手段探索未知的分子生物学机理并鉴定全新的生物医药靶点，进而开发尚未满足临床需求(Unmet Medical Needs)的原始创新（First-in-Class）药物,如抑制乙肝病毒感染，生物钟调节，小分子诱导蛋白降解等。

Total Synthesis of Natural product:

Inspired by the rapid and efficient construction of molecular complexity from simple precursors in natural living system by enzymatic pathway, our lab is mainly focused on the biocatalysis development and the utilization of biomimetic synthesis of natural products and biologically valuable small molecules. The utility of biomass-derived building blocks will be demonstrated by the synthesis of a variety of natural products through environmentally friendly organocascade process that involve the formation of several chemical bonds and stereogenic centers simultaneously with excellent stereoselectivity. Structurally complex natural products are naturally produced in microorganisms through a series of elaborate biological pathways, so its biomimetic synthesis will be incorporated with organocascade transformations in the lab.

Medicinal Chemistry:

Besides discovery of small molecule catalysis and natural product biomimetic synthesis, we are also interested in developing novel reagents for practical transformations to rapidly assemble unnatural complex molecules. The combination of chemical synthesis and biosynthesis of biologically valuable molecules is an important part of our pursuits for exciting discoveries of biomaterials, chemical biology as well as pharmaceutical agents to solve serious health problem in living system.

High-Throughput Screening：

HTS is a drug-discovery process widely used in the pharmaceutical companies and biomedical research institutes. Using robotics, data processing and control software, liquid handling devices and sensitive detectors, HTS conduct extremely scalable assay to test the biological or biochemical activity of a large number of small molecules for discovering active agents for receptors, enzymes, ion-channels or other pharmacological targets in the molecular and cellular level of biomolecular pathway. Typically, HTS assays are performed in microtiter plates with a 96 or 384 well format. HTS is one of main facilities in our lab to provide comprehensive services including the use of HTS technology, compounds in various libraries, a database of results from screens and lead optimization. On a collaborative basis, HTS has the capability to support cellular and biochemical assays using absorbance, fluorescent kinetics, fluorescence resonance energy transfer, AlphaScreen, bioluminescence and cellular fluorescence imaging. In addition, HTS has expertise in adapting those biological and biochemical bench-top assays into high-throughput screening settings.  Our HTS libraries are designed for diversity around not only well-established pharmacophore, but also very strict molecular property profiles that were balanced between diversity, physicochemical favorability, intrinsic complexity, and synthetic tractability. Encouraged by the fact that a significant number of marketed drugs are derived from natural products, we are also interested in expanding natural chemical products in compound libraries and developing effective strategy to diversify the core backbone structure of natural products. We will design and explore biomimetric synthetic pathways to build up the molecule efficiently. Easily modified structure and high selective strategy will be preferred. The organocascade type assembling of complex structure will eventually result in the discovery of novel bio-valuable molecules to diversify the library.

Novel Synthetic Methodology：

Saturation of carbon or heteroatoms, especially sp3-hybridized and stereogenic atoms in pharmacophore allows the preparation of architecturally more complex molecules for the exploration of more diverse chemical space. While biological activity of small molecule and clinical success are highly correlated with greater complexity of the molecule, the increasing sp3 character of carbon may improve the complexity and therefore increase the opportunity to adjust molecular shape by out-of-plane 3-D interaction of receptor/ligand that are not accessible for a flat aromatic ring, and thus improve potency and selectivity. While aromatic features can provide an opportunity to develop π-π interactions or π-cation interactions, an overall level of saturation may provide the molecule with an opportunity to better place these types of moieties in a 3D environment, which is generally observed in binding pockets of target proteins.

These criteria have also been applied to molecular complexity of natural product-like drug candidates by reducing the aromatic character of a molecule, which might further improve physical characteristics not only for better druggability, but also for better bioavailability. In our lab, we mainly focus on the synthetic logic and strategy for the activation, functionalization and formation of sp3-carbon-carbone single bond.

Carbon-carbon single bonds are among the most abundant and the strongest inert bonds in organic compounds. Activating them for chemical modification is one of the most challenging problems in organic synthesis. Furthermore, the selective activation or cleavage of the terminal vs. internal C-C single bonds of aliphatic chain is still unsolved! In addition, the presence of more active C-H bond is superimposed obstacle for selective activation of C-C bond.

SP3-C-C single bond activation:

http://qigroup.nibs.ac.cn/publications/

1. 1.      Huan Yan, Lei Zhang, YangLiu, Guoliang Sun, GuangWei Xu, Zilin Song, Wenhui Li*, and Xiangbing Qi* “Potent, persistent, and selective inhibition of human NTCP-mediated HBV infection by bile acid derivatives”,manuscript in preparation.
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3.  2.      Chao Yang, Songlin Bai, Chao Jiang* and Xiangbing Qi*, “Asymmetric synthesis alkylbora derivatives via enantioselectiove cross-coupling of gem-Borazirconocene Alkanes”, manuscript in preparation.
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5.  3.      Xiaolei Liu, Mingliang Lou, and Xiangbing Qi*, “Asymmetric Total Synthesis of (-)-Dehydrotubifoline through a de-aromatization/Fischer indole strategy”，Journal of the American Chemical Society, Submitted
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7.  4.      Lu Lv, Peihao Chen, Longzhi Cao, Yamei Li, ZhiZeng, Yue Cui, Qingcui Wu, Jiaojiao Li, Jian-Hua Wang, Meng-Qiu Dong, Xiangbing Qi* and Ting Han*, “Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger Cyclin K  degradation”, in press, elife

1.  5.      Youwei Ai, Haibing He, Peihao Chen, Bo Yan,Wenbin Zhang, Zhangcheng Ding, Dianrong Li, Jie Chen, Yan Ma, Yang Cao, JieZhu, Jiaojiao Li, Jinjie Ou, Shan Du, Xiaodong Wang, Jianzhang Ma, Shuanhu Gao* and Xiangbing Qi* , “An alkaloid initiates phosphodiesterase 3A–schlafen12 dependent apoptosis without affecting the phosphodiesterase activity”, Nature communication, 28 Jun. 2020: https://www.nature.com/articles/s41467-020-17052-4.pdf

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2.  6.      Chao Yang, Yadong Gao, Songlin Bai, ChaoJiang* and Xiangbing Qi*, “Chemoselective Cross-coupling of gem-Borazirconocene Alkanes with Aryl Halides”, Journal of the American Chemical Society, 2020, 142, 26, 11506-11513

1.  7.      Dapeng Ju, Wei Zhang, JiaweiYan, Haijiao Zhao, Wei Li, Jiawen Wang, Meimei Liao, Zhancong Xu, Zhiqiang Wang, Guanshen Zhou, LongMei, Nannan Hou, Shuhua Ying, Tao Cai, SheChen, Xiaowen Xie, Luhua Lai, Chao Tang, Noheon Park, Joseph S. Takahashi, Niu Huang, Xiangbing Qi* and Eric Erquan Zhang*, “Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals”, Science Translational Medicine 06 May 2020: 12, Issue 542, eaba0769; DOI: 10.1126/scitranslmed.aba0769

1.     8.      YadongGao, Jianhua Li, Songlin Bai, Daoquan Tu, Chao Yang, Zhiwen Ye, Bingcheng Hu, Xiangbing Qi* and Chao Jiang*, “Direct Synthesis of Annulated Indoles through Palladium-Catalyzed Double Alkylations” Org.Chem. Front., 2020, DOI: 10.1039/D0QO00135J

1.  9.      YadongGao, Chao Yang, Sonlin Bai, Xiaolei Liu, Qingcui Wu, Chao jiang*, Xiangbing Qi*, “Visible-light-induced Nickel-Catalyzed Cross-coupling with Alkylzirconocenes from Unactivated Alkenes” Chem, 2020，675.

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2.  10.   Ran Cao,Li Li, Zhengxin Ying, Zichen Cao, Yongfen Ma, Xiaoxu Mao,Jiaojiao Li, Xiangbing Qi, Zhiyuan Zhang, and Xiaodong Wang*.”A small molecule protects mitochondrial integrity by inhibiting mTOR activity” Proceedings of the National Academy of Sciences, 2019, 116 (46), 23332.
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4.  11.   XiaofeiShen#, Lin Zhao#, Peihao Chen#, Yanqiu Gong, Dingdong Liu, Xia Zhang, LunzhiDai, Qingxiang Sun, Jizhong Lou, Zhong Jin, Baohua Zhang, Dawen Niu, CeshiChen, Xiangbing Qi, Da Jia* “A thiazole-derived oridonin analog exhibits antitumor activity by directly and allosterically inhibiting STAT3” The Journal of Biological Chemistry, 2019, 294, 17471.
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6.  12.   QiqiChu, Changfu Yao, Xiangbing Qi, Barry Raymond Stripp, Nan Tang* “STK11 is required for the normal program of ciliated cell differentiation in airways” Cell Discovery (2019)5:36, 1.
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8.  13.   DianrongLi, Jie Chen, Youwei Ai, Xiaoqiong Gu, Li Li, Di Che, Zhaodi Jiang, Lin Li, SheChen, Huangwei Huang, Jiawen Wang, Tao Cai, Yang Cao, Xiangbing Qi, Xiaodong Wang*, “Estrogen-Related Hormones Induce Apoptosis by Stabilizing Schlafen-12 Protein Turnover” Molecular Cell, 2019, 1103.

1.  14.   Meiyi Zhou, Shao Jing, Cheng-Yang Wu, Le Shu, Weibing Dong, Yunxia Liu, Mengping Chen, R. Max Wynn, Jiqiu Wang, Ji Wang, Wen-Jun Gui, Xiangbing Qi, Aldons J. Lusis, Zhaoping Li, Weiqing Wang, Guang Ning, Xia Yang, David T. Chuang, Yibin Wang, Haipeng Sun*, “Targeting BCAA Catabolism to Treat Obesity-Associated Insulin Resistance” Diabetes 2019, 68(9),1730.
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3.  15.   Lei Zhang, Ye Zhang, Wenting Li, Xiangbing Qi*, “Total Synthesis of(-)-Alstofolinine A through a Furan Oxidation/Rearrangement and Indole Nucleophilic Cyclization Cascade” Angew. Chem. Int. Ed. 2019, 4988.

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2.  16.   Li Li , Yue Zhao, RanCao, Lin Li, Gaihong Cai, Jiaojiao Li, Xiangbing Qi, She Chen and Zhiyuan Zhang*, “Activity-based protein profiling reveals GSTO1 as the covalent target of piperlongumine and a promising target for combination therapy for cancer”, Chem. Commun., 2019,4407.
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4.  17.   Hang Fu,Nan Liu, Qiang Dong, Chunxiao Ma, Jing Yang, Jun Xiong, Zhuqiang Zhang, Xiangbing Qi, Chang Huang & Bing Zhu*. “SENP6-mediated M18BP1 deSUMOylation regulates CENP-A centromeric localization” Cell Research 2019, 254.
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6.    18.   Yu Zhou, Yuanxun Wang, PengfeiLi, Xi-Ping Huang, Xiangbing Qi, Yunfei Du*, and Niu Huang*. “Exploring Halogen Bonds in5-Hydroxytryptamine 2B Receptor–Ligand Interactions” ACS Med. Chem. Lett., 2018, 9, 1019.
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8.  19.  ChaoWei, Xiao Han, Danwei Weng, Qiru Feng, Xiangbing Qi, Jin Li & Minmin Luo. “Response dynamics of mid brain dopamine neurons and serotonin Interactions neurons to heroin, nicotine, cocaine, and MDMA” Cell Discovery，2018，1019.
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10.  20.   Aaron Nash, Xiangbing Qi, Pradip Maity, Kyle Owens, and Uttam K. Tambar*.“Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)‐Lundurine A” Angew. Chem. Int. Ed.,2018, 57, 6888.

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2.  21.      RuiLin, Qiru Feng, Peng Li, Ping Zhou, Ruiyu Wang, Zhe Liu, Zhiqiang Wang, Xiangbing Qi, Nan Tang, Feng Shao,Minmin Luo, “A hybridization-chain-reaction-based method for amplifying immuno signals” Nature Methods, 2018 (4),275.

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2.  22.   Cheng-Yang Wu, Santhosh Satapati, Wenjun Gui,R Max Wynn, Gaurav Sharma, Mingliang Lou, Xiangbing Qi, Shawn C Burgess, Craig Malloy, Chalermchai Khemtong, A Dean Sherry,David T Chuang, Matthew E Merritt, “A novel inhibitor of pyruvate dehydrogenasekinase stimulates myocardial carbohydrate oxidation in diet-induced obesity”, The Journal of Biological Chemistry, 2018, 293, 9604.
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4.  23.   Cheng-Yang Wu, Shih-Chia Tso, Jacinta LChuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David TChuang，“Targeting hepatic pyruvate dehydrogenase kinases restores insulin signaling and mitigates ChREBP-mediated lipogenesis indiet-induced obese mice”，Molecular Metabolism, 2018, 12.
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6.  24.   Xuekai Zhang, Gang Lu, Meng Sun, MadhuMahankali, Yanfei Ma, Mingming Zhang, Wangde Hua, Yuting Hu, Qingbing Wang,Jinghuo Chen, Gang He, Xiangbing Qi*,Weijun Shen*, Peng Liu*, Gong Chen*，“A general strategy for synthesis of cyclophane-braced peptide macrocycles via palladium-catalysed intramolecular sp3 C-H arylation”， Nature Chemistry，2018, 540.

1.  25.   Xueyan Ma, Peixue Li, Peihao Chen, Jinhui Li,Hongling Huang, Chao Wang, Wenjing Li, Jianping Ding, Yun Zhao, Fa-Xing Yu, Xiangbing Qi*, Lei Zhang*，“Staurosporine targets the Hippo pathway to inhibit cell growth” Journal of Molecular Cell Biology, 2018, 10, 267.

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2.  26.   JingjingFu, Yadong Gao, Xiangbing Qi*, Chao Jiang* “Synthesis of Polysubstituted Pyridines and Indoles by a Palladium-Catalyzed Catellani-type Alkylation-Alkenylation Sequence” Chemistry Select, 2018,10164
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4.  27.   Yanli Wang, Yuze Sun, Ran Cao, Dan Liu, YutingXie, Li Li, Xiangbing Qi*, Niu Huang*， “In Silico Identification of a Novel Hinge-Binding Scaffold for Kinase Inhibitor Discovery” J. Med. Chem., 2017, 60 (20), 8552.

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2.  28.     Shih-ChiaTso, Mingling Lou, Wen-Jun Gui , Cheng-Yang Wu, Jacinta L. Chuang, Lorraine K.Morlock, Noelle S. Williams, R. Max Wynn, XiangbingQi* and David T. Chuang* “Development of Dihydroxyphenyl Sulfonylisoindoline Derivatives as Liver-targeting Pyruvate Dehydrogenase Kinase Inhibitors” J. Med. Chem., 2017, 60 (3), 1142.

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2.  29.     YalingWu, Dingbin Tang, Na Liu, Wei Xiong, Huanwei Huang, Yang Li, Zhixiong Ma, HaijiaoZhao, Peihao Chen, Xiangbing Qi and Eric ErquanZhang*. “Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals”,Cell Metabolism, 2017, 25(1), 73.
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4.  30.     Shih-Chia Tso, Wen-Jun Gui, Cheng-YangWu, Jacinta L. Chuang, XiangbingQi, Kristen J. Skvorak, Kenneth Dorko, Amy L.Wallace, Lorraine K. Morlock, Brendan H. Lee, Susan M.Hutson, Stephen C. Strom, Noelle S. Williams, Uttam K.Tambar, R. Max Wynn, and David T. Chuang. “Benzothiophene Carboxylate Derivatives as Novel Allosteric Inhibitors of Branched-chainα-Ketoacid Dehydrogenase Kinase” J. Biol.Chem., 2014, 289,20583.
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6.  31.     Shih-ChiaTso*, Xiangbing Qi*,Wen-Jun Gui, Cheng-Yang Wu, Jacinta L. Chuang, Ingrid Wernstedt-Asterholm,Lorraine K. Morlock, Kyle R. Owens, Philipp E. Scherer, Noelle S. Williams,Uttam K. Tambar, R. Max Wynn and David T. Chuang. “Structure-guided Development of Specific Pyruvate Dehydrogenase Kinase Inhibitors Targeting the ATP-bindingPocket”.  J. Biol.Chem. 2014, 289,4432. (* Equal Contribution)
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8.  32.     Shih-chiaTso*, Xiangbing Qi*,Wen-Jun Gui, Jacinta L. Chuang, Lorraine K. Morlock, Amy L. Wallace, KamranAhmed, Sunil Laxman, Philippe M. Campeau, Brendan H. Lee, Susan M. Hutson,Benjamin P. Tu, Noelle S. Williams, Uttam K. Tambar, R. Max Wynna, and David T.Chuang. , “Structure-based Design and Mechanisms of Allosteric Inhibitors for Mitochondrial Branched-chainα-Ketoacid Dehydrogenase Kinase.” Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 9728. (* Equal Contribution)
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10.  33.     Yi Liu, Jun Liu*, Xiangbing Qi*, and Yuguo Du* “One-Pot Synthesis of 2,4-Disubstituted Thiazoline from β-AzidoDisulfide and Carboxylic Acid” J. Org. Chem., 2012, 7108.
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12.  34.     Feng Cai, Xiaotao Pu, Xiangbing Qi, Joseph. M. Ready*.“Allenes in Asymmetric Catalysis: Asymmetric Addition of Boronic Acid to α-ketoesters Catalyzed by Allene-Containing Rhodium-Phosphine Catalyst”. J. Am. Chem. Soc., 2011, 133, 18066.
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14.  35.     Xiangbing Qi, Hongli Bao, UttamK.Tambar*. “Total Synthesis of (±)-Trigonoliimine C via Oxidative Rearrangement of an Unsymmetrical Bis-Tryptamine”, J.Am. Chem. Soc. 2011, 133,10050-10053.
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16.  36.     Hongli Bao, Xiangbing Qi, Uttam K.Tambar*.“Catalytic Enantioselective [2,3]-Rearrangements of Amine N-Oxides ”, J. Am. Chem. Soc. 2011, 133, 1206.
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18.  37.     Xiangbing Qi, Grant T. Rice,Manjinder S. Lall, Mark S. Plummer, M. Christina White* “Diversification of aβ-lactam Pharmacophore via Allylic C–H Amination: Accelerating Effect of Lewis Acid co-catalyst”, Tetrahedron, 2010, 66, 4816.
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20.  38.     Xiaotao Pu, Xiangbing Qi, Joseph. M. Ready*.“Allenes in Asymmetric Catalysis: Asymmetric Ring Opening of meso-Epoxides Catalyzed by Allene-Containing Phosphine Oxides” J. Am. Chem. Soc. 2009, 131, 10364.
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22.  39.     Xiangbing Qi, Joseph. M. Ready*.“Synthesis of Cyclopentenones from Cyclopropanes and Silyl Ynol Ethers” Angew. Chem. Int. Ed. 2008, 47, 7068.
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24.  40.     Xiangbing Qi, Joseph. M. Ready*.“Copper-Promoted Cycloaddition of Diazocarbonyl Compounds with CopperAcetylides” Angew. Chem. Int. Ed. 2007, 46, 3242.