COS-triggered Oxygen/Sulfur Exchange of Isatins: Chemoselective Synthesis of Functionalized Isoindigos and Spirothiopyrans via Self-condensation and Thio-Diels-Alder Reaction

Herein, we present the first organocatalytic oxygen/sulfur atom exchange reaction (O/S ER) of isatins by employing carbonyl sulfide (COS) as novel sulfuring reagent under mild reaction conditions. 8-Diazabicyclo[5.4.0] undec-7-ene (DBU),...

Modular and stereoselective synthesis of tetrasubstituted vinyl sulfides leading to a library of AIEgens

Tetraarylethylenes exhibit intriguing photophysical properties and sulfur atom frequently play a vital role in organic photoelectric materials and biologically active compounds. Tetrasubstituted vinyl sulfides, which include both sulfur atom and tetrasubstituted alkenes motifs, might be a suitable skeleton for the discovery of the new material molecules and drug with unique functions and properties. However, how to modular synthesis these kinds of compounds is still challenging. Herein, a chemo- and stereo-selective Rh(II)-catalyzed [1,4]-acyl rearrangements of α-diazo carbonyl compounds and thioesters has been developed, providing a modular strategy to a library of 63 tetrasubstituted vinyl sulfides. In this transformation, the yield is up to 95% and the turnover number is up to 3650. The mechanism of this reaction is investigated by combining experiments and density functional theory calculation. Moreover, the “aggregation-induced emission” effect of tetrasubstituted vinyl sulfides were also investigated, which might useful in functional material, biological imaging and chemicalnsing via structural modification.

1,3,4-thiadiazole: a privileged scaffold for drug design and development

: 1,3,4-thiadiazole is a five-membered aromatic heterocycle containing two nitrogen atoms and one sulfur atom. As a privileged scaffold, it has its unique chemical properties and biological characteristics. In the design of drugs, they are widely and flexibly applied by medicinal chemists, and many candidates with therapeutic prospects have been developed. In this review, we focus on 1,3,4-thiadiazole derivatives and their various biological activities reported in the past five years (from 2015 to early 2020), such as anticancer, antibacterial, antifungal, anti-tuberculosis, anti-inflammatory, antivirus, anti-leishmania and other functions. It is believed that this review can provide some new ideas for seeking rational design to develop 1,3,4-thiadiazole based medicinal agents with better activity and lower toxicity.

A New Synthetic Route to (Trifluoromethyl)quinolines: Nickel-Catalyzed Insertion of an Alkyne into an Aromatic C–S Bond by Formation of a Thianickelacycle and Thermal Desulfidation

We have developed a nickel-catalyzed insertion reaction of an alkyne into a 2-(trifluoromethyl)-1,3-benzothiazole to give a seven-membered benzothiazepine that is converted into a 2-(trifluoromethyl)quinoline by thermal desulfidation. This process can be considered a formal substitution of a sulfur atom with an alkyne. The structure of the thianickelacycle intermediate formed through oxidative addition of a C–S bond in the benzothiazole to nickel(0) was confirmed by X-ray single-crystal structure analysis and in situ X-ray absorption fine-structure spectroscopy.

A Novel Family of [1,4]Thiazino[2,3,4-ij]quinolin-4-ium Derivatives: Regioselective Synthesis Based on Unsaturated Heteroatom and Heterocyclic Compounds and Antibacterial Activity

A novel family of [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives was synthesized by annulation reactions of 8-quinolinesulfenyl chloride with unsaturated heteroatom and heterocyclic compounds. It was found that the reactions with 4-pentenoic and 5-hexenoic acids, allyl chloride and bromide, allyl cyanate and vinyl heterocyclic compounds (N-vinyl pyrrolidin-2-one and 1-vinylimidazole) proceeded in a regioselective mode but with the opposite regiochemistry. The reactions with vinyl heterocyclic compounds included electrophilic addition of the sulfur atom of 8-quinolinesulfenyl chloride to the β-carbon atom of the vinyl group. In the case of other substrates, the annulation proceeded with the attachment of the sulfur atom to the α-carbon atom of the vinyl group. The antibacterial activity of novel water-soluble compounds against Enterococcus durans, Bacillus subtilis and Escherichia coli was evaluated. Compounds with high antibacterial activity were found.

A DFT Study on the Molecular Mechanism of Additions of Electrophilic and Nucleophilic Carbenes to Non-Enolizable Cycloaliphatic Thioketones

The molecular mechanisms of addition of dihalocarbenes and dimethoxycarbene to thioketones derived from 2,2,4,4-tetrmethylcyclobutane-1,3-dione were examined on the basis of the DFT wb97xd/6-311g(d,p)(PCM) calculations. Obtained results demonstrated that the examined processes exhibit polar nature and in the case of electrophilic dichloro-, and dibromocarbenes are initiated by the attack of carbene species onto the sulfur atom of the C=S group. Remarkably, reactions involving more electrophilic carbenes (dichloro-, and dibromocarbene) proceeds via stepwise mechanism involving thiocarbonyl ylide as a transient intermediate. In contrast, analogous reactions with nucleophilic dimethoxycarbene occur via a single step reaction, which can be considered as the [2 + 1] cycloaddition reaction initiated by the attack onto the C=S bond. A computational study showed that difluorocarbene tends to react as a nucleophilic species and resembles rather dimethoxycarbene and not typical dihalocarbene species. Significantly higher reactivity of the thioketone unit in comparison to the ketone group, both present in 3-thioxo-2,2,4,4-tetramthylcyclobutanone molecule, was rationalized in the light of DFT computational study.

Thionation of Aminophthalimide Hindered Carbonyl Groups and Application to the Synthesis of 3,6′-Dithionated Pomalidomides

Herein, we present a new one-pot procedure for the 3,6′-dithionation of pomalidomide derivatives in which the key 3-position sulfur atom is preferentially installed at the desired (but sterically congested) carbonyl of the aminophthalimide system and with regiochemistry distinct from Lawesson’s Reagent thionation methods. When heated in 1,4-dioxane with P4S10–pyridine complex, pomalidomides are smoothly and reproducibly converted into their 3,6′-dithionated analogues in roughly 30% isolated yield and at various scales. While detrimental to the desired 3,6′-type outcome when employing Lawesson’s Reagent, we hypothesize that the pomalidomide aniline group instead facilitates P4S10-type thionation at the otherwise hindered 3-position carbonyl, contributing to the selectivity observed. When paired with classical methods of thionation, this approach offers an interesting and appealing addition to the synthetic toolbox, permitting facile late-stage access to complementary thionated pomalidomides in direct single-flask procedures.

Examining the Underappreciated Role of S-Acylated Proteins as Critical Regulators of Phagocytosis and Phagosome Maturation in Macrophages

Phagocytosis is a receptor-mediated process used by cells to engulf a wide variety of particulates, including microorganisms and apoptotic cells. Many of the proteins involved in this highly orchestrated process are post-translationally modified with lipids as a means of regulating signal transduction, membrane remodeling, phagosome maturation and other immunomodulatory functions of phagocytes. S-acylation, generally referred to as S-palmitoylation, is the post-translational attachment of fatty acids to a cysteine residue exposed topologically to the cytosol. This modification is reversible due to the intrinsically labile thioester bond between the lipid and sulfur atom of cysteine, and thus lends itself to a variety of regulatory scenarios. Here we present an overview of a growing number of S-acylated proteins known to regulate phagocytosis and phagosome biology in macrophages.