Electrophilic Thiocyanation of Tryptamine Derivatives: Divergent Synthesis of SCN-Containing Indole Compounds.

A tandem dearomative electrophilic thiocyanation/cyclization/acylation of indoles was developed for the first time, which is enabled by acyl chloride. A variety of 3-SCN pyrroloindolines were obtained with moderate to excellent yields. Interestingly, following replacement of acyl chloride with methanesulfonic acid, 2-SCN tryptamines were obtained using the same starting substrates and reagents. Furthermore, catalytic enantioselective manner of thiocyanation/cyclization/acylation reaction was also studied. An enantiomer self-disproportionation effect of 3-SCN pyrroloindolines was discovered. A series of chiral 3-SCN pyrroloindolines were obtained with high enantioselectivities.

Lewis-Acid-Mediated Intramolecular Trifluoromethylthiolation of Alkenes with Phenols: Access to SCF3-Containing Chromane and Dihydrobenzofuran Compounds.

A Lewis-acid-mediated intramolecular trifluoromethylthiolation of alkenes with phenols that can offer direct access to SCF3-containing chromane and dihydrobenzofuran compounds was disclosed for the first time. Numerous SCF3-containing chromanes were obtained in moderate to good yields using γ-substituted 2-allyphenols as substrates. Meanwhile, various SCF3-containing dihydrobenzofurans with oxa-quaternary centers were also delivered in moderate to good yields using ß-substituted 2-allyphenols as substrates.

Coumarin derivatives with anticancer activities: An update.

Cancer can invade or spread to almost all parts of the body. The increasing morbidity and high mortality of cancer create a great demand for the development of novel anticancer drugs. Coumarin derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond interactions; hence, coumarin is a highly privileged pharmacophore for the development of novel anticancer agents. This review will focus on the recent development of coumarin hybrids as potential anticancer agents covering articles published from 2019 to 2020.

Lewis-Acid-Mediated Thiocyano Semipinacol Rearrangement of Allylic Alcohols for Construction of α-Quaternary Center ß-Thiocyano Carbonyls.

An electrophilic thiocyano semipinacol rearrangement of allylic alcohols has been achieved for the first time by using N-thiocyano-dibenzenesulfonimide (NTSI). This approach provides a direct, simple, and efficient strategy for the formation of thiocyano carbonyl compounds with moderate to excellent yields. Meanwhile, an all-carbon quaternary center was rapidly constructed. In addition, an asymmetric version of this tandem reaction was preliminarily investigated.

Lewis Base/Brønsted Acid Co-Catalyzed Asymmetric Thiolation of Alkenes with Acid-Controlled Divergent Regioselectivity.

A divergent strategy for the facile preparation of various enantioenriched phenylthio-substituted lactones was developed based on Lewis base/Brønsted acid co-catalyzed thiolation of homoallylic acids. The acid-controlled regiodivergent cyclization (6-endo vs. 5-exo) and acid-mediated stereoselective rearrangement of phenylthio-substituted lactones were explored. Experimental and computational studies were performed to clarify the origins of the regioselectivity and enantioselectivity. The calculation results suggest that C-O and C-S bond formation might occur simultaneously, without formation of a commonly supposed catalyst-coordinated thiiranium ion intermediate and the potential π-π stacking between substrate and SPh as an important factor in the enantio-determining step. Finally, this methodology was applied in the rapid syntheses of the bioactive natural products (+)-ricciocarpin A and (R)-dodecan-4-olide.

Lewis base-catalyzed asymmetric sulfenylation of alkenes: construction of sulfenylated lactones and application to the formal syntheses of (-)-nicotlactone B and (-)-galbacin.

An efficient method for the preparation of chiral sulfenylated lactones has been described based on Lewis base-catalyzed enantioselective sulfenylation of unsaturated carboxylic acids. The scope of this method includes two enantioselective cyclization reactions: 5-endo and 6-exo thiolactonizations of alkenes. Two types of lactones were obtained with up to 95% ee and 99% yield. Additionally, this methodology has been applied in the formal syntheses of bioactive natural products (-)-nicotlactone B and (-)-galbacin.

TMSCl-Catalyzed Electrophilic Thiocyano Oxyfunctionalization of Alkenes Using N-Thiocyano-dibenzenesulfonimide.

Numerous electrophilic thiocyano oxyfunctionalization reactions of alkenes have been achieved using N-thiocyano-dibenzenesulfonimide, which is a new electrophilic thiocyanation reagent and could be easily prepared in two steps from dibenzenesulfonimide. This approach provides efficient, simple, and modular methods for the formation of SCN-containing heterocycles such as lactones, tetrahydrofurans, dihydrofurans, and dihydrobenzofurans in moderate to excellent yields. Meanwhile, diverse oxa-quaternary centers were rapidly constructed. Additionally, this protocol is free of transition metals and features broad substrate toleraance and mild reaction conditions.

Recent advances of pyrazole-containing derivatives as anti-tubercular agents.

One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium tuberculosis (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles. Numerous of pyrazole-containing derivatives have been synthesized for searching new anti-TB agents, and some of them showed promising potency and may have novel mechanism of action. This review aims to outline the recent achievements in pyrazole-containing derivatives as anti-TB agents and their structure-activity relationship.

Azide-alkyne cycloaddition towards 1H-1,2,3-triazole-tethered gatifloxacin and isatin conjugates: Design, synthesis and in vitro anti-mycobacterial evaluation.

Twelve novel 1H-1,2,3-triazole-tethered gatifloxacin (GTFX) isatin conjugates 5a-l with greater lipophilicity compared with GTFX were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The preliminary results showed that all the targets (MIC: 0.10-8 µg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but eight of them (CC50: 7.8-62.5 µg/mL) were much more toxic than the parent GTFX (CC50: 125 µg/mL). Among them, 5g (MIC: 0.10 µg/mL) was 4-8 times more potent in vitro than the references GTFX (MIC: 0.78 µg/mL) and RIF (MIC: 0.39 µg/mL) against MTB H37Rv, but less active than INH (MIC: 0.05 µg/mL). The most potent 5g and 5h (MIC: 0.25 µg/mL) were 4->512 times more active than the three references (MIC: 1.0->128 µg/mL) against MDR-TB. Unfortunately, both of the two hybrids (CC50: 7.8 µg/mL) were much more cytotoxic than the other derivatives, need to be further optimized.

Synthesis, characterization and spectral properties of substituted tetraphenylporphyrin iron chloride complexes.

A series of substituted tetraphenylporphyrin iron chloride complexes [RTPPFe(III)Cl, R=o/p-NO2, o/p-Cl, H, o/p-CH3, o/p-OCH3] were synthesized by a novel universal mixed-solvent method and the spectral properties of free base porphyrins and iron porphyrin compounds were compared with each other. The experimental results showed that the one-pot mixed solvent method was superior to the two-step method in the yields, reaction time and workup of reaction mixtures for the synthesis of iron porphyrin compounds. The highest yields (28.7%-40.4%) of RTPPFe(III)Cl were obtained in the mixed solvents propionic acid, glacial acetic acid and m-nitrotoluene under reflux for 2 h. A detailed analysis of ultraviolet-visible (UV-vis), infrared (IR) and far-infrared (FIR) spectra suggested the transformation from free base porphyrins to iron porphyrins. The red shift of the Soret band in ultraviolet-visible spectra due to the presence of p-nitrophenyl substituents and the blue shift of Fe-Cl bond of TPPFeCl in far-infrared spectra were further explained by the electron transfer and molecular planarity in the porphyrin ring.