Peking University Shenzhen Graduate School

Shenzhen, China

Peking University Shenzhen Graduate School

Shenzhen, China
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Cheng G.-J.,Peking University Shenzhen Graduate School | Zhang X.,Peking University Shenzhen Graduate School | Chung L.W.,South University of Science and Technology of China | Xu L.,Peking University Shenzhen Graduate School | And 2 more authors.
Journal of the American Chemical Society | Year: 2015

Understanding the mechanisms of chemical reactions, especially catalysis, has been an important and active area of computational organic chemistry, and close collaborations between experimentalists and theorists represent a growing trend. This Perspective provides examples of such productive collaborations. The understanding of various reaction mechanisms and the insight gained from these studies are emphasized. The applications of various experimental techniques in elucidation of reaction details as well as the development of various computational techniques to meet the demand of emerging synthetic methods, e.g., C-H activation, organocatalysis, and single electron transfer, are presented along with some conventional developments of mechanistic aspects. Examples of applications are selected to demonstrate the advantages and limitations of these techniques. Some challenges in the mechanistic studies and predictions of reactions are also analyzed. © 2015 American Chemical Society.


Chen K.,Peking University Shenzhen Graduate School | Zhang X.,Peking University Shenzhen Graduate School | Wu Y.-D.,Peking University Shenzhen Graduate School | Wu Y.-D.,Peking University | And 2 more authors.
Journal of the American Chemical Society | Year: 2014

Histone deacetylases (HDACs) have found intense interest as drug targets for a variety of diseases, but there is disagreement about basic aspects of the inhibition and mechanism of HDACs. QM/MM calculations of HDAC8 including a large QM region provide a model that is consistent with the available crystal structures and structure-activity relationships of different HDAC inhibitors. The calculations support a spontaneous proton transfer from a hydroxamic acid to an active site histidine upon binding to the zinc. The role of the H142/D176 catalytic dyad as the general base of the reaction is elucidated. The reasons for the disagreements between previous proposals are discussed. The results provide detailed insights into the unique mechanism of HDACs, including the role of the two catalytic dyads and function of the potassium near the active site. They also have important implications for the design of novel inhibitors for a number of HDACs such as the class IIa HDACs. © 2014 American Chemical Society.


Wei H.,Peking University Shenzhen Graduate School | Qiao C.,Peking University Shenzhen Graduate School | Liu G.,Peking University Shenzhen Graduate School | Yang Z.,Peking University Shenzhen Graduate School | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2013

Convergent approach: The total syntheses of (-)-flueggine A and (+)-virosaine B (see scheme) have been accomplished in a concise and convergent manner. Key steps in these approaches were relay ring-closing metathesis reactions for rapid construction of the key intermediates, and 1,3-dipolar cycloaddition reactions for the formation of the natural products. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


An K.,Xiamen University | Zhu J.,Xiamen University | Zhu J.,Peking University Shenzhen Graduate School
European Journal of Organic Chemistry | Year: 2014

Aromaticity, one of the most important concepts in chemistry, has attracted considerable interest from both experimentalists and theoreticians. According to Baird's rule, triplet annulenes with 4n π electrons are aromatic. However, the approach to evaluate the magnitude of the triplet aromaticity is less developed. Herein we apply the indene-isoindene isomerization stabilization energy (ISE) method to evaluate the aromaticity in the triplet state. The reliability of this approach can be demonstrated by the strong correlation of these indene-isoindene ISE values with nucleus-independent chemical shifts [NICS(1)zz] as well as methyl-methylene ISE values. Large [4n]annulenes have the tendency to be planar to achieve aromaticity in the T1 state. Steric effects play an important role in the stabilities of large [4n]annulene isomers. Triplet aromaticity has been evaluated by applying the indene-isoindene isomerization stabilization energy (ISE) method. The reliability of this approach can be demonstrated by the strong correlation of ISE values with NICS(1)zz as well as the previous methyl-methylene ISE values. Our results verify Baird's rule: that triplet annulenes with 4n π-electrons are aromatic. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Meng L.,Wuhan University | Wu K.,Wuhan University | Liu C.,Wuhan University | Lei A.,Wuhan University | Lei A.,Peking University Shenzhen Graduate School
Chemical Communications | Year: 2013

The first palladium-catalysed aerobic oxidative intramolecular alkenylation of Csp3-H bonds was described. The reaction conditions were mild and molecular oxygen was used as the terminal oxidant. Kinetic studies showed that the Csp3-H metallation step was a slow step. © 2013 The Royal Society of Chemistry.


Han J.-C.,South University of Science and Technology of China | Li F.,Peking University Shenzhen Graduate School | Li C.-C.,South University of Science and Technology of China | Li C.-C.,Peking University Shenzhen Graduate School
Journal of the American Chemical Society | Year: 2014

A new method has been developed for the concise and asymmetric synthesis of seven humulanolides in 5-7 steps without the need for protecting groups. Notably, the challenging 11-membered ring and bridged butenolide moieties in asteriscunolide D and 6,7,9,10-tetrahydroasteriscunolide were introduced in one step using a ring-opening/ring-closing metathesis cascade reaction. Asteriscunolide D was used as a versatile synthetic precursor to prepare asteriscunolides A-C via a photoinduced isomerization reaction, asteriscanolide via a unique transannular Michael reaction, and 6,7,9,10-tetradehydroasteriscanolide via a transannular Morita-Baylis-Hillman-type reaction. The unique bicyclo[6.3.0]undecane core was introduced diastereoselectively. © 2014 American Chemical Society.


Zhang Y.,Peking University Shenzhen Graduate School | Luo T.,CAS Beijing National Laboratory for Molecular | Yang Z.,Peking University Shenzhen Graduate School | Yang Z.,CAS Beijing National Laboratory for Molecular
Natural Product Reports | Year: 2014

Novel organic reactions drive the advance of chemical synthesis in the same way that enabling technologies drive new scientific discoveries. One area of organic methodology that has undergone significant growth during the last decade is that of homogeneous gold-catalyzed transformations. This trend has been further enhanced by the employment of gold catalysis on a routine basis to accomplish the total synthesis of natural products. In particular, the superior π acidity of the cationic gold complex for the activation of alkynes and allenes towards nucleophilic addition has significantly enriched the toolkit of transformations available to the total synthesis community, and inspired a new era of creativity in terms of the strategic disconnection of target compounds during their retrosynthetic analysis. Instead of simply supplementing the many existing reviews of gold catalysis, this review has been organized from the perspective of synthetic target families, with particular emphasis on the use of gold-catalyzed transformations during the late stages of syntheses involving complicated substrates, and cascade reactions that significantly increase molecular complexity. This journal is © the Partner Organisations 2014.


Wang C.,Peking University Shenzhen Graduate School | Huang Y.,Peking University Shenzhen Graduate School
Synlett | Year: 2013

The need to use a static directing group represents a major limitation for the emerging field of ortho-selective C-H activation and functionalization. Chemistry was recently developed that allowed partial removal or minor transformations for certain directing groups. Our recent work demonstrated that triazenes were a class of excellent directing groups for C-H activation/functionalization, and subsequent chemical manipulations generated key compounds with synthetic versatility. © Georg Thieme Verlag Stuttgart · New York.


Xu J.,Peking University Shenzhen Graduate School | Shen C.,Peking University Shenzhen Graduate School | Wang T.,Peking University Shenzhen Graduate School | Quan J.,Peking University Shenzhen Graduate School
Nature Structural and Molecular Biology | Year: 2013

Polo-like kinase 1 (PLK1) is a master regulator of mitosis and is considered a potential drug target for cancer therapy. PLK1 is characterized by an N-terminal kinase domain (KD) and a C-terminal Polo-box domain (PBD). The KD and PBD are mutually inhibited, but the molecular mechanisms of the autoinhibition remain unclear. Here we report the 2.3-Å crystal structure of the complex of the Danio rerio KD and PBD together with a PBD-binding motif of Drosophila melanogaster microtubule-associated protein 205 (Map205 PBM). The structure reveals that the PBD binds and rigidifies the hinge region of the KD in a distinct conformation from that of the phosphopeptide-bound PBD. This structure provides a framework for understanding the autoinhibitory mechanisms of PLK1 and also sheds light on the activation mechanisms of PLK1 by phosphorylation or phosphopeptide binding. © 2013 Nature America, Inc. All rights reserved.


Wang X.-L.,Peking University Shenzhen Graduate School | Quan J.-M.,Peking University Shenzhen Graduate School
Journal of the American Chemical Society | Year: 2011

BluB is a distinct flavin destructase that catalyzes a complex oxygen-dependent conversion of reduced flavin mononucleotide (FMNH2) to form 5,6-dimethylbenzimidazole (DMB), the lower ligand of vitamin B 12. The catalyzed mechanism remains a challenge due to the discrepancy between the complexity of the conversion and the relative simplicity of the active site of BluB. In this study, we have explored the detailed conversion mechanism by using the hybrid density functional method B3LYP on an active site model of BluB consisting of 144 atoms. The results indicate that the conversion involves more than 14 sequential steps in two distinct stages. In the first stage, BluB catalyzes the incorporation of dioxygen, and the fragmentation of the isoalloxazine ring of FMNH2 to form alloxan and the ribityl dimethylphenylenediimine (DMPDI); in the second stage, BluB exploits alloxan as a multifunctional cofactor, such as a proton donor, a proton acceptor, and a hydride acceptor, to catalyze the remaining no fewer than 10 steps of the reaction. The retro-aldol cleavage of the C1′-C2′ bond of DMPDI is the rate-determining step with a barrier of about 21.6 kcal/mol, which produces D-erythrose 4-phosphate (E4P) and the ring-closing precursor of DMB. The highly conserved residue Asp32 plays critical roles in multiple steps of the conversion by serving as a proton acceptor or a proton shuttle, and another conserved residue Ser167 plays its catalytic role mainly in the rate-determining step by stabilizing the protonated retro-aldol precursor. These results are consistent with the available experimental observations. More significantly, the novel intermediate-assisted mechanism not only provides significant insights into understanding the mechanism underlying the power of the simple BluB catalyzing the complex conversion of FMNH2 to DMB, but also represents a new type of intermediate-assisted multifunctional catalysis in an enzymatic reaction. © 2011 American Chemical Society.

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