Regiodivergent and Enantioselective Hydroxylation of C−H bonds by Synergistic Use of Protein Engineering and Exogenous Dual-Functional Small Molecules

It is a great challenge to optionally access diverse hydroxylation products from a given substrate bearing multiple reaction sites of sp³ and sp² C−H bonds. Herein, we report the highly selective divergent hydroxylation of alkylbenzenes by an engineered P450 peroxygenase driven by a dual-functional small molecule (DFSM). Using combinations of various P450BM3 variants with DFSMs enabled access to more than half of all possible hydroxylated products from each substrate with excellent regioselectivity (up to >99 %), enantioselectivity (up to >99 % ee), and high total turnover numbers (up to 80963). Crystal structure analysis, molecular dynamic simulations, and theoretical calculations revealed that synergistic effects between exogenous DFSMs and the protein environment controlled regio- and enantioselectivity. This work has implications for exogenous-molecule-modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry.     

A one-pot chemoenzymatic synthesis of (2S, 4R)-4-methylproline enables the first total synthesis of antiviral lipopeptide cavinafungin B

We report an efficient ten-step (longest linear sequence) synthesis of antiviral natural product cavinafungin B in 37% overall yield. By leveraging a one-pot chemoenzymatic synthesis of (2S,4R)-4-methylproline and oxazolidine-tethered (AT (Boc)G-Rink resin) SPPS methodology, the assembly of our molecular target could be conducted in an efficient manner. This general strategy could prove amenable to the construction of other natural and unnatural linear lipopeptides. The value of incorporating biocatalytic steps in complex molecule synthesis is highlighted by this work.     

杂多化合物对苯酚羟化制苯二酚反应的催化性能

研究了１５种杂多化合物对苯酚羟化反应的催化活性，其中具有Ｋｅｇｇｉｎ结构的稀土四元杂多化合物催化效果最好，苯酚的转化率达４１．６６％，对苯二酚产率达４０．２４％。     

微米级MEL分子筛聚集体的制备

使用四丁基氢氧化铵-正硅酸四乙酯-水（TBAOH-TEOS-H₂O）简单体系一步水热制备了具有多级孔道的微米级MEL结构分子筛聚集体. 得到的silicalite-2 微米球直径大于10 μm且具有高达460 m²·g^-1的比表面积和0.74 cm³·g^-1的孔体积. 微米球的生成一定程度上解决了催化应用过程中催化剂的分离和回收问题. 同时,水热晶化过程中由纳米粒子自组装而成的晶间介孔缩短了反应物分子的扩散路径,保持了分子筛纳米晶粒的优势. 此外,钛活性位的引入并未明显影响MEL微米球的形貌和结构,含钛的MEL微米球TS（钛硅分子筛）-2在苯酚羟基化反应中具有与纳米尺寸TS-1（100-200 nm）相当的催化活性,且TS-2 可以通过简单过滤得到,简化了纳米级TS-1的分离和回收过程.     

A molecular route towards silica supported zirconium catalysts active for the mild oxidation of olefins with H2O2

A series of Zr based catalysts were synthesized using tetraneopentylzirconium as precursor complex and a silica partially dehydroxylated. Modifications of the Zr coordination sphere of the anchored complex, (SiO)ZrNp₃ (Np = neopentyl), by hydrolysis or hydrogenolysis lead to catalysts showing unexpected activity for the expoxidation of cyclohexene and hydroxylation of phenol with H₂O₂.     

Preparation of phenolic compounds through catalyst-free ipso-hydroxylation of arylboronic acids

A novel method for the preparation of phenolic compounds through ipso-hydroxylation of the corresponding widely available arylboronic acid precursors is described. Through application of a novel PEG400-H₂O₂ reactant system, a variety of substituted phenols and other aromatic analogues have been prepared in excellent yields at room temperature in the absence of any catalyst.     

Syntheses of Prekinamycin and a Tetracyclic Quinone from Common Synthetic Intermediates

Towards total synthesis of a series of kinamycin and related antibiotics via common synthetic intermediates, total synthesis of prekinamycin was achieved via Suzuki coupling of naphthaleneboronic acid and bromobenzene derivative, intramolecular Friedel? Crafts reaction of 2‐(naphthalen‐2‐yl)benzoic acid, and diazotization in ten steps from 3,5‐dimethylphenol. Synthetic studies towards kinamycin antibiotics was also examined, and the tetracyclic quinone core for kinamycins was synthesized. Palladium‐catalyzed site‐selective hydroxylation of a benzoic acid derivative with the AB‐D ring part was successfully applied to the selective D‐ring functionalizations.     

Characterization of atenolol transformation products in ozonation by using rapid resolution high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry

This experiment investigated the transformation pathway of atenolol, a widely used β-blocker, in the ozonation process through the identification of generated intermediate compounds. In order to characterize the contribution of ozone and hydroxyl radical (•OH) in the transformation of atenolol, ozonation were performed at pH 2, 7 and 9. 15 major transformation products have been identified based on the chromatographic behavior of these compounds and the information obtained from accurate mass MS and MS/MS spectra. By comparing to the elution pattern of the identified transformation products and its fragmentation pattern in the MS/MS spectrum, a variety of isomers of the transformation products were characterized.Identified transformation products of atenolol are including its mono-, di and tri-hydroxylated derivatives as well as the aliphatic and aromatic ring breakdown products. Transformation of atenolol in the ozonation involved hydroxylation reaction, aromatic ring opening reaction, oxidation and cleavage of 2-hydroxy-3-(isopropylamino)propoxy group of atenolol. In ozonation, aromatic ring of atenolol was transformed through the reaction with both ozone and •OH whereas the aliphatic chain of atenolol was degraded mainly through the reaction with •OH. The results also indicated that both •OH and ozone involved in the aromatic ring opening reaction.     

Effect of calcination temperature on the structure and hydroxylation activity of Ni0.5Cu0.5Fe2O4 nanoparticles

Nanocrystalline Ni_0.5Cu_0.5Fe₂O₄ was synthesized by sol-gel method with varying calcination temperature over the range of 500-1000. The powders obtained were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). In addition, thermal analysis (TG-DTG-DTA) of the precursor was carried out. The study reveals the simultaneous decomposition and ferritization process at rather low temperature (280-350). For the crystalline structure investigated, single cubic spinel is gained when the precursor was decomposed at 800-1000, whereas separated crystal CuO formed when calcination temperature is below 800. The increase of calcination temperature favors the appearance of Fe_B³⁺, Cu_A²⁺ and O on the spinel surface. The hydroxylation activity is relative to the amount of Cu_B²⁺ species on the spinel surface. The lattice oxygen species on the spinel surface are favorable for the deep oxidation of phenol.