High‐Throughput Proteomics Enabled by a Photocleavable Surfactant

Mass spectrometry (MS)‐based proteomics provides unprecedented opportunities for understanding the structure and function of proteins in complex biological systems; however, protein solubility and sample preparation before MS remain a bottleneck preventing high‐throughput proteomics. Herein, we report a high‐throughput bottom‐up proteomic method enabled by a newly developed MS‐compatible photocleavable surfactant, 4‐hexylphenylazosulfonate (Azo) that facilitates robust protein extraction, rapid enzymatic digestion (30 min compared to overnight), and subsequent MS‐analysis following UV degradation. Moreover, we developed an Azo‐aided bottom‐up method for analysis of integral membrane proteins, which are key drug targets and are generally underrepresented in global proteomic studies. Furthermore, we demonstrated the ability of Azo to serve as an “all‐in‐one” MS‐compatible surfactant for both top‐down and bottom‐up proteomics, with streamlined workflows for high‐throughput proteomics amenable to clinical applications.     

Continuous Consecutive Reactions with Inter‐Reaction Solvent Exchange by Membrane Separation

Pharmaceutical production typically involves multiple reaction steps with separations between successive reactions. Two processes which complicate the transition from batch to continuous operation in multistep synthesis are solvent exchange (especially high‐boiling‐ to low‐boiling‐point solvent), and catalyst separation. Demonstrated here is membrane separation as an enabling platform for undertaking these processes during continuous operation. Two consecutive reactions are performed in different solvents, with catalyst separation and inter‐reaction solvent exchange achieved by continuous flow membrane units. A Heck coupling reaction is performed in N,N‐dimethylformamide (DMF) in a continuous membrane reactor which retains the catalyst. The Heck reaction product undergoes solvent exchange in a counter‐current membrane system where DMF is continuously replaced by ethanol. After exchange the product dissolved in ethanol passes through a column packed with an iron catalyst, and undergoes reduction (>99 % yield).     

The Many Roles of Quantum Chemical Predictions in Synthetic Organic Chemistry

This account discusses representative case studies for various applications of quantum chemical calculations in synthetic organic chemistry. These include confirmation of target structures, methodology development, and catalyst design. These examples demonstrate how predictions from quantum chemical calculations can be utilized to streamline synthetic efforts.     

促进高中学生有机化学素养发展的复习课教学活动设计——以“合成高分子化合物”为例

在教学价值及学情分析的基础上，确定了学生有机化学素养发展在"合成高分子化合物"上的生长点。由滴眼液引入，围绕其主要成分设计问题情境，通过一系列的教学活动发展了学生对高分子化合物的合成方法及合成路线设计、高分子化合物的"链节"和"聚合度"等基本概念及高分子化合物的应用等的认识。     

Synthesis of New Lipid‐Inspired Ionic Liquids by Thiol‐ene Chemistry: Profound Solvent Effect on Reaction Pathway

The synthesis of a series of new lipid‐inspired ionic liquids through thiol‐ene “click” reaction with a single‐step process. This synthesis offers considerable promise as an efficient and orthogonal method to construct structurally diverse imidazolium‐type ionic liquids with linear and branched cationic tails, as well as versatility in the placement of the sulfur heteroatom. Profound solvent effect in this ene reaction regioselectivity has been observed.     

Synthesis of Fragment Derivatives of Delta Sleep-inducing Peptide （1-4） Catalyzed by Enzymes in Organic Solvents

Synthesis of two fragment derivatives of delta sleep-inducing peptide (DSIP) (1-4), Boc-Trp-Ala-Gly-GlyNHNHPh (1) and Boc-Trp-Ala-Gly-GlyOEt (2), catalyzed by proteases via 2 2 or 1 3 synthetic routes with different protecting groups at C-terminal in organic solvents was reported. The yield of N-Boc tetrapeptide with phenylhydrazinyl protecting carboxyl group at C-terminal (1) was higher than that of N-Boc tetrapeptide ethyl ester (2) by 2 2 route. The factors influencing the synthetic yield of the fragments of DSIP (1-4) were discussed.     

3D Printed High‐Throughput Hydrothermal Reactionware for Discovery,Optimization, and Scale‐Up

3D printing techniques allow the laboratory‐scale design and production of reactionware tailored to specific experimental requirements. To increase the range and versatility of reactionware devices, sealed, monolithic reactors suitable for use in hydrothermal synthesis have been digitally designed and realized. The fabrication process allows the introduction of reaction mixtures directly into the reactors during the production, and also enables the manufacture of devices of varying scales and geometries unavailable in traditional equipment. The utility of these devices is shown by the use of 3D printed, high‐throughput array reactors to discover two new coordination polymers, optimize the synthesis of one of these, and scale‐up its synthesis using larger reactors produced on the same 3D printer. Reactors were also used to produce phase‐pure samples of coordination polymers MIL‐96 and HKUST‐1, in yields comparable to synthesis in traditional apparatus.     

饮料及配制酒中11种有机合成色素的低共熔溶剂萃取/高效液相色谱法测定

采用四丁基氯化铵和辛酸合成新型疏水性低共熔材料,并以其为萃取剂建立了快速测定饮料、配制酒中11种有机合成色素的高效液相色谱方法。样品经水稀释,以200μL低共熔溶剂萃取后,采用高效液相色谱-二极管阵列检测器(HPLC-DAD)检测,外标法定量。结果表明,11种有机合成色素在各自的质量浓度范围内均呈良好的线性关系,相关系数(r~2)均大于0.996,检出限为0.03～0.31 mg/kg,定量下限为0.08～1.02 mg/kg;加标回收率为92.6%～103%,相对标准偏差(RSD)为0.98%～4.3%。该方法快速、简便、精准,适用于饮料、配制酒中有机合成色素的检测。     

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty‐Chemicals Manufacturing

The recent uptake of molecular metathesis catalysts in specialty‐chemicals and pharmaceutical manufacturing is reviewed.     

4‐Methyltetrahydropyran (4‐MeTHP): Application as an Organic Reaction Solvent

4‐Methyltetrahydropyran (4‐MeTHP) is a hydrophobic cyclic ether with potential for industrial applications. We herein report, for the first time, a comprehensive study on the performance of 4‐MeTHP as an organic reaction solvent. Its broad application to organic reactions includes radical, Grignard, Wittig, organometallic, halogen‐metal exchange, reduction, oxidation, epoxidation, amidation, esterification, metathesis, and other miscellaneous organic reactions. This breadth suggests 4‐MeTHP can serve as a substitute for conventional ethers and harmful halogenated solvents. However, 4‐MeTHP was found incompatible with strong Lewis acids, and the C?O bond was readily cleaved by treatment with BBr₃. Moreover, the radical‐based degradation pathways of 4‐MeTHP, THP and 2‐MeTHF were elucidated on the basis of GC‐MS analyses. The data reported herein is anticipated to be useful for a broad range of synthetic chemists, especially industrial process chemists, when selecting the reaction solvent with green chemistry perspectives.     

Rapid Syntheses of (−)‐FR901483 and (+)‐TAN1251C Enabled by Complexity‐Generating Photocatalytic Olefin Hydroaminoalkylation

We report a common strategy to facilitate the syntheses of the polycyclic alkaloids (?)‐FR901483 ( 1 ) and (+)‐TAN1251C ( 2 ). A divergent synthetic strategy provides access to both natural products through a pivotal spirolactam intermediate ( 3 ), which can be accessed on a gram‐scale. A photocatalytic olefin hydroaminoalkylation brings together three readily available building blocks and forges the majority of the carbon framework present in 1 and 2 in a single operation, leading to concise total syntheses. The complexity‐generating photocatalytic process also provides direct access to novel non‐racemic spirolactam scaffolds that are likely to be of interest to early‐stage drug discovery programs.     

Lithium‐Doped 3D Covalent Organic Frameworks: High‐Capacity Hydrogen Storage Materials

Quick on the uptake : A multiscale theoretical method predicts that the gravimetric adsorption capacities of H₂ in Li‐doped covalent organic frameworks based on the building blocks shown (Li violet, H white, B pink, C green, O red, Si yellow) can reach nearly 7 % at T=298 K and p=100 bar, suggesting that these Li‐doped materials are promising adsorbents for hydrogen storage.