Biomimetic Hydrogenation Catalyzed by a Manganese Model of [Fe]‐Hydrogenase

[Fe]‐hydrogenase is an efficient biological hydrogenation catalyst. Despite intense research, Fe complexes mimicking the active site of [Fe]‐hydrogenase have not achieved turnovers in hydrogenation reactions. Herein, we describe the design and development of a manganese(I) mimic of [Fe]‐hydrogenase. This complex exhibits the highest activity and broadest scope in catalytic hydrogenation among known mimics. Thanks to its biomimetic nature, the complex exhibits unique activity in the hydrogenation of compounds analogous to methenyl‐H₄MPT⁺, the natural substrate of [Fe]‐hydrogenase. This activity enables asymmetric relay hydrogenation of benzoxazinones and benzoxazines, involving the hydrogenation of a chiral hydride transfer agent using our catalyst coupled to Lewis acid‐catalyzed hydride transfer from this agent to the substrates.     

Divergent Biomimetic Total Syntheses of Ganocins A–C,Ganocochlearins C and D,and Cochlearol T

A divergent synthetic approach to six Ganoderma meroterpenoids, namely ganocins A–C, ganocochlearins C and D, and cochlearol T, has been developed for the first time. This synthetic route features a two‐phase strategy which includes early‐stage rapid construction of a common planar tricyclic intermediate followed by highly selective late‐stage transformations into various Ganoderma meroterpenoids. Key to the strategy are a bioinspired intramolecular hetero‐Diels–Alder reaction and Stahl‐type oxidative aromatization, allowing efficient formation of the common tricyclic phenol intermediate. A nucleophilic dearomatization of the phenol unit, combined with a regioselective 1,4‐reduction of the resulting dienone, enabled rapid access to ganocins B and C. Additionally, site‐selective Mukaiyama hydration, followed by an intramolecular oxa‐Michael addition/triflation cascade, served as a key strategic element in the chemical synthesis of ganocin A.     

Complex Polypropionates from a South China Sea Photosynthetic Mollusk: Isolation and Biomimetic Synthesis Highlighting Novel Rearrangements

Placobranchus ocellatus is well known to produce diverse and complex γ‐pyrone polypropionates. In this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery and identification of ocellatusones A–D, a series of racemic non‐γ‐pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane ( 1 , 2 ), a bicyclo[3.3.1]nonane ( 3 ) or a mesitylene‐substituted dimethylfuran‐3(2H)‐one core ( 4 ). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X‐ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1 – 4 after chiral HPLC resolution. An array of new and diversity‐generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co‐occurring γ‐pyrones ( 5 – 10 ). Furthermore, the successful biomimetic semisynthesis of ocellatusone A ( 1 ) confirmed the proposed rearrangement through an unprecedented acid induced cascade reaction.     

Imitation of drug metabolism in cell co-culture microcapsule model using a microfluidic chip platform coupled to mass spectrometry

In this work,a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry(MS) detector was described.We constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor treatment.On this specially designed integrated platform,the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture,and the second step was to achieve on-line perfusion culture and continuous drug stimulation on chip.It facilitates cell proliferation analysis and the collection of metabolism medium.After micro solid phase extraction column(SPE) pretreatment,subsequent mass spectrometry could detect drug metabolism.The high activity of two kinds of cells(A549 and HUVEC) shows the biocompatibility of the platform.Paclitaxel was used as a model drug,the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry(ESI-Q-TOF MS).Therefore,the integrated platform has shown promise as a high throughput,low cost for cell metabolism research and drug screening processes.     

Total Syntheses of (−)-Minovincine and (−)-Aspidofractinine through a Sequence of Cascade Reactions

We report 8-step syntheses of (−)-minovincine and (−)-aspidofractinine using easily available and inexpensive reagents and catalyst. A key element of the strategy was the utilization of a sequence of cascade reactions to rapidly construct the penta- and hexacyclic frameworks. These cascade transformations included organocatalytic Michael-aldol condensation, a multistep anionic Michael-S_N2 cascade reaction, and Mannich reaction interrupted Fischer indolization. To streamline the synthetic routes, we also investigated the deliberate use of steric effect to secure various chemo- and regioselective transformations.     

Catalyst-Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides

The biomimetic synthesis of aromatic polyketides from macrocyclic substrates by means of catalyst-controlled transannular cyclization cascades is described. The macrocyclic substrates, which feature increased stability and fewer conformational states, were thereby transformed into several distinct polyketide scaffolds. The catalyst-controlled transannular cyclizations selectively led to aromatic polyketides with a defined folding and oxygenation pattern, thus emulating β-keto-processing steps of polyketide biosynthesis.     

A Green and Wide-Scope Approach for Chiroptical Sensing of Organic Molecules through Biomimetic Recognition in Water

Optical chirality sensing has attracted a lot of interest due to its potential in high-throughput screening in chirality analysis. A molecular sensor is required to convert the chirality of analytes into optical signals. Although many molecular sensors have been reported, sensors with wide substrate scope remain to be developed. Herein, we report that the amide naphthotube-based chirality sensors have an unprecedented wide scope for chiroptical sensing of organic molecules. The substrates include, but are not limited to common organic products in asymmetric catalysis, chiral molecules with inert groups or remote functional groups from their chiral centers, natural products and their derivatives, and chiral drugs. The effective chirality sensing is based on biomimetic recognition in water and on effective chirality transfer through guest-induced formation of a chiral conformation of the sensors. Furthermore, the sensors can be used in real-time monitoring on reaction kinetics in water and in determining absolute configurations and ee values of the products in asymmetric catalysis.     

Aerobic Double Dehydrogenative Cross Coupling between Cyclic Saturated Ketones and Simple Arenes

The synthesis of 3‐aryl‐2‐cyclohexenones is a topic of current interest as they are not only privileged structures in bioactive molecules, but they are also relevant feedstocks for the synthesis of substituted phenols or anilines, which are ubiquitous structural elements both in drug design and medicinal chemistry. A simple and sustainable one‐pot aerobic double dehydrogenative reaction under mild conditions for the introduction of arenes in the β‐position of cyclic ketones has been developed. Starting from the corresponding saturated ketone, this reaction sequence proceeds under relatively low Pd catalyst loading and involves catalytic amounts of electron‐transfer mediators (ETMs) under ambient oxygen pressure.     

On the Reaction Mechanism of the Complete Intermolecular O2 Transfer between Mononuclear Nickel and Manganese Complexes with Macrocyclic Ligands

The recently described intermolecular O₂ transfer between the side‐on Ni‐O₂ complex [(12‐TMC)Ni‐O₂]⁺ and the manganese complex [(14‐TMC)Mn]²⁺, where 12‐TMC and 14‐TMC are 12‐ and 14‐membered macrocyclic ligands, 12‐TMC=1,4,7,10‐tetramethyl‐1,4,7,10‐tetraazacyclododecane and 14‐TMC=1,4,8,11‐tetramethyl‐1,4,8,11‐tetraazacyclotetradecane, is studied by means of DFT methods. B3LYP calculations including long‐range corrections and solvent effects are performed to elucidate the mechanism. The potential energy surfaces (PESs) compatible with different electronic states of the reactants have been analyzed. The calculations confirm a two‐step reaction, with a first rate‐determining bimolecular step and predict the exothermic character of the global process. The relative stability of the products and the reverse barrier are in line with the fact that no reverse reaction is experimentally observed. An intermediate with a μ‐η¹:η¹‐O₂ coordination and two transition states are identified on the triplet PES, slightly below the corresponding stationary points of the quintet PES, suggesting an intersystem crossing before the first transition state. The calculated activation parameters and the relative energies of the two transition sates and the products are in very good agreement with the experimental data. The calculations suggest that a superoxide anion is transferred during the reaction.