The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented.

A palladium-catalyzed regiodivergent C1 insertion multicomponent reaction involving aryne, CO, and 2-iodoaniline is established to construct the scaffolds of phenanthridinone and acridone alkaloids. Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand-free condition. In comparison, application of the electron-abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method.

A palladium-catalyzed multicomponent reaction (MCR) involving aryne, CO, and aniline is established for straightforward assembly of a phenanthridinone scaffold through C-H bond activation. Free combination with multiple kinds of readily available anilines and arynes is facilely achieved for phenanthridinone construction without prefunctionalization. Representative natural products were subsequently synthesized through this MCR strategy highly efficiently. Control experiments and interval NMR tracking revealed the mechanism, particularly the key role of CuF2 in determining the aryne-releasing rate from the precursor in this transformation.

a b s t r a c tDesymmetrization synthesis strategy has simplified and improved the efficiency of synthesis, which attracted great attention in the past few decades. Since the strategy has been developed rapidly and got a wide range of applications in natural product total synthesis, the rules are urgent to be summarized. In this Letter, the recent developments of desymmetrization protocol in natural product total synthesis were summarized.

Novel, temperature-responsive molecularly imprinted polymers (TMIPs) based on potassium hexatitanate whiskers for selectively adsorbing sulfadiazine (SDZ) from aqueous media were prepared with methacrylic acid (MAA) and 4-vinylpyridine (4-VP) as cofunctional monomers and N-isopropyl acrylamide (NIPAM) as a temperature-responsive monomer. The template-monomer interactions were studied by molecular simulation. In particular, the effects of different kinds of crosslinkers on the selective recognition ability of the TMIPs in water media were investigated. The temperature-responsive adsorption performance and phase behavior of the molecularly imprinted polymers were studied by batch-mode binding experiments, swelling experiments, and contact angle testing. The results demonstrate that the combination of MAA, 4-VP, and NIPAM was a favorable temperature-responsive imprinted system for SDZ in water, and the cocrosslinking agent of ethylene glycol dimethacrylate (EGDMA) and N,N 0 -methylene bisacrylamide (MBA) was more suitable compared with either pure EGDMA or MBA. The adsorption kinetics and adsorption isotherms were analyzed by the fitting of different adsorption models. Also, the effect of the temperature on the recovery was investigated by the determination of the spiked SDZ in real-water samples with solid-phase extraction and high-performance liquid chromatography.