Deconstructive and Divergent Synthesis of Bioactive Natural Products.

Natural products play a key role in innovative drug discovery. To explore the potential application of natural products and their analogues in pharmacology, total synthesis is a key tool that provides natural product candidates and synthetic analogues for drug development and potential clinical trials. Deconstructive synthesis, namely building new, challenging structures through bond cleavage of easily accessible moieties, has emerged as a useful design principle in synthesizing bioactive natural products. Divergent synthesis, namely synthesizing many natural products from a common intermediate, can improve the efficiency of chemical synthesis and generate libraries of molecules with unprecedented structural diversity. In this review, we will firstly introduce five recent and excellent examples of deconstructive and divergent syntheses of natural products (2021-2023). Then, we will summarize our previous work on the deconstructive and divergent synthesis of natural products to demonstrate the high efficiency and simplicity of these two strategies in the field of total synthesis.

A long-wavelength fluorescent probe with a large Stokes shift for lysosome-targeted imaging of Cys and GSH.

Biothiols including cysteine (Cys) and glutathione (GSH) are biological signaling molecules responsible for cell detoxification, cell metabolism and neutralization of reactive oxygen species. Here, we synthesized a long-wavelength fluorescent probe, DCIMA, for lysosome-targeted imaging of Cys and GSH in living cells. DCIMA is consisted of a dicyanoisophorone core modified with an acrylate group for biothiol detection through the Michael addition reaction and a morpholine group as the lysosome-targeting agent. The presence of the electron-donating morpholine group also enhances the intramolecular charge transfer mechanism of the probe, thereby enabling its long-wavelength fluorescence emission (670 nm) and large Stokes shift (180 nm). In concentration range of 0-30 µM, the probe was determined to react quickly with both Cys and GSH with low detection limits (<5 min, 35.2 nM for GSH and 34.8 nM for Cys) and achieve the sensitive fluorescence imaging of the biothiols located in the lysosomes of living cells.

Research on the Effect of Molten Salt Ultrasonic Composite Cleaning for Paint Removal.

Aiming at paint removal on hydraulic cylinder, the effect of molten salt ultrasonic composite cleaning was studied. First, the mechanism of molten salt cleaning and ultrasonic cleaning was reviewed. To further describe the composite cleaning mechanism, the components and internal structure of paint were analyzed by scanning electron microscopy and Fourier transform infrared. Results showed that the paint had a significant layered structure. The total thickness was about 100 µm, and the main components were organic matters, including ester groups, epoxy groups, and aromatic compounds. Then, combining with thermal environment, cleaning medium's property, and ultrasound, the composite cleaning mechanism was described in terms of three aspects: thermal effect, chemical reaction, and ultrasonic effect. Besides, the reason why this composite cleaning had good effect on paint removal, compared to paint heated in air, was explained through dynamic analysis, which was the reduction of reaction activation energy from 114.4 kJ/mol of paint alone to 74.1 kJ/mol.

AND-Logic Based Fluorescent Probe for Selective Detection of Lysosomal Bisulfite in Living Cells.

Sulfur dioxide (SO2) plays significant roles in regulating cell apotosis and inflammation. However, there are complex interactions between small biomolecules in cells, and the identification of these coexisting biomarkers remains a challenge. Herein, we report an AND logic gate based fluorescent probe (NY-Lyso), operating by responding to pH differences between organelles in cell and selectively reacting with bisulfite (HSO3-). This approach allows the fluorescence of the probe to remain silent under neutral or alkaline conditions, notably, is activated by costimulation of lower pH and bisulfite. Furthermore, it was confirmed to be biocompatible and could be employed to monitor HSO3- in lysosomes of living cells. The proposed method demonstrated more practical and outstanding capabilities in targeted and real-time monitoring, providing an effective optical tool for biomarker sensing.