Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis

This work is dedicated to 100th anniversary of Xiamen University and its Chemistry.手性α-芳基酮，是一个非常重要的药效官能团，广泛存在于药物分子中，虽然含有α-季碳手性中心的芳基酮的不对称合成已经有较多报道，但是相应的具有α-叔碳手性中心的芳基酮的高效不对称合成依然极具挑战性，因为相对活泼的叔碳手性中心很容易发生外消旋化。霍浩华教授课题组在前期工作的基础上（JACS, 2020, 142, 19058.），经过一系列探索，成功将“溴自由基介导的C-H活化策略”由α-氨基sp3 C-H键拓展至苄位sp3 C-H键，在镍和光的协同催化下，实现了首例不对称苄位C(sp3)-H的酰基化反应。该研究工作在霍浩华教授指导下完成，博士研究生环磊桃和束晓敏为该论文的共同第一作者，博士研究生祖维赛和硕士研究生钟德参与了部分研究工作。Asymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.We are grateful for financial support from the NSFC (22071203) and the Xiamen University. We thank professor Hai-Chao Xu (Xiamen University) for assistance and helpful discussions. We acknowledge Wesley Harrison (UIUC) for manuscript revision.研究工作得到了国家高层次青年人才项目、厦门大学南强A计划、国家自然科学基金委项目（No. 22071203）的资助

Behavior changes of rats with syndrome of stagnation of liver qi and spleen deficiency after injecting microcrystalline BDNF in bilateral DG areas and regulation of active fraction of Xiaoyao Powder

目的:从行为学角度探讨逍遥散有效部位治疗肝郁脾虚证的调节机制。方法:60只雄性SD大鼠随机等分为5组:正常组、模型组、假手术组、脑源性神经营养因子(BDNF)组、逍遥散组。以21d慢性束缚应激方法塑造大鼠肝郁脾虚证模型,在此基础上,运用脑立体定位仪埋管微量注射BDNF塑造BDNF组。逍遥散组造模方法和BDNF组尽可能相似,突出逍遥散有效部位和BDNF二者干预的可比性,第1、7、14、21天分别比较BDNF组和逍遥散组反映行为变化的各项指标变化趋势是否一致。结果:模型组大鼠逐步呈现肝郁脾虚证表现;假手术组大鼠开始呈现焦躁状态,第14-21天,逐步和模型组行为表现趋同;BDNF组起到干预治疗作用,大鼠焦躁状态得到抑制;逍遥散组大鼠表现自然,逍遥散有效部位起到较好的调节作用。排除了手术创伤等混杂因子,逍遥散组和BDNF组经过21d治疗后穿格数、站立次数、修饰次数变化趋势逐步相似。结论:逍遥散有效部位和BDNF可能有一条作用通路相似,即可能均通过BDNF信号通路来治疗肝郁脾虚证。Objective: To explore the mechanism of active fraction of Xiaoyao Powder in treating rats with syndrome of stagnation of liver qi and spleen deficiency. Methods: Sixty SD male rats were randomly divided into 5 groups as control group, model group, sham-operation group, BDNF group and Xiaoyao Powder group. The rat models with syndrome of stagnation of liver qi and spleen deficiency were established by using method of chronic immobilization stress(CIS) for 21 days. On the basis, rats in BDNF group received injection with microcrystalline BDNF in bilateral DG areas with the help of stereotaxic apparatus. The model establishing methods of Xiaoyao Powder and BDNF groups were as similar as possible, in order to highlight the comparability in intervention between active fraction of Xiaoyao Powder and BDNF. The variation trend of behavior indicators of rats in Xiaoyao Powder group and BDNF group was compared on the 1st, 7th, 14 th, and 21 st day. Results: The symptoms of ‘syndrome of stagnation of liver qi and spleen deficiency' appeared progressively in rats of the model group. Rats in shamoperation group were in anxiety states at the beginning, and the symptoms were basically the same with model group from the 14 th to 21 th day. Anxiety state of rats in BDNF group was inhibited. The behaviors of rats in Xiaoyao Powder group were nature, which showed that active fraction of Xiaoyao Powder could play a good adjustment effect. Eliminating the influence of surgical trauma, the crossing times, standing times, and licking frequency of rats in Xiaoyao Powder group and BDNF group after treating for 21 days were basically the same. Conclusion: From the above results of behaviores, it concludes that there is a similar action pathway between active fraction of Xiaoyao Powder and BDNF, and both might treat syndrome of stagnation of liver qi and spleen deficiency by BDNF signaling pathway.国家自然科学基金青年基金项目(No.81302960)~

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies