Catalytic (4+2) Annulation via Regio- and Enantioselective Interception of in-situ Generated Alkylgold Intermediate.

A regio- and stereoselective stepwise (4+2) annulation of N-propargylamides and α,ß-unsaturated imines/ketones has been accomplished with synergetic catalysis by a combination of a gold-complex and a chiral quinine-derived squaramide (QN-SQA), leading to highly functionalized chiral tetrahydropyridines/dihydropyrans in good to high yields with generally excellent enantioselectivity. Mechanistic studies and DFT calculations indicate that the in situ formed alkylgold species is the key intermediate in this transformation, and the amide group served as a traceless directing group in this highly selective transformation. This method complements the enantioselective (4+2) annulation of allene reagents, providing the formal internal C-C π-bond cycloaddition products, which is challenging and remains elusive.

Artificial Channels Based on Bottlebrush Polymers: Enhanced Ion Transport Through Polymer Topology Control.

Synthetic structures mimicking the transport function of natural ion channel proteins have a wide range of applications, including therapeutic treatments, separation membranes, sensing, and biotechnologies. However, the development of polymer-based artificial channels has been hampered due to the limitation on available models. In this study, we demonstrate the great potential of bottlebrush polymers as accessible and versatile molecular scaffolds for developing efficient artificial ion channels. Adopting the bottlebrush configuration enhanced ion transport activity of the channels compared to their linear analogs. Matching the structure of lipid bilayers, the bottlebrush channel with a hydrophilic-hydrophobic-hydrophilic triblock architecture exhibited the highest activity among the series. Functionalized with urea groups, these channels displayed high anion selectivity. Additionally, we illustrated that the transport properties could be fine-tuned by modifying the chemistry of ion binding sites. This work not only highlights the importance of polymer topology control in channel design, but also reveals the great potential for further developing bottlebrush channels with customized features and diverse functionalities.

A diastereoselective three-component reaction for the assembly of succinimide and isatin hybrid molecules with potent anticancer activities.

A Rh2(OAc)4 catalyzed three-component reaction of vinyl diazosuccinimides with alcohols and isatins has been reported, which provides a practical assess to the direct assembly of succinimide and isatin hybrid molecules in good-to-high yields with excellent stereoselectivity. The antiproliferation activity of these synthesized succinimide and isatin hybrid products has been tested via the CCK8 assay in different cancer cell lines, and compounds 4g (SJSA-1, IC50 = 3.82 µM) and 4r (HCT-116, IC50 = 9.02 µM) exhibit higher anticancer potency than other tested compounds.

Construction of Chiral Quaternary Carbon Centers via Asymmetric Metal Carbene gem-Dialkylation.

The catalytic asymmetric construction of all-carbon quaternary stereocenters has received tremendous interest over the past decades, and numerous efficient protocols have been disclosed based on the formation of one C-C bond between two assembling reactants. However, the use of asymmetric multi-component reactions that build two C-C bonds on the same carbonic center with concomitant assembly of quaternary stereocenters is rare and remains challenging. Herein, we disclose an enantioselective three-component reaction of α-diazo ketones with alkenes and 1,3,5-triazines under dirhodium/chiral phosphoric acid cooperative catalysis, which leads to a practical and atom-economic synthesis of poly-functionalized chiral ketones that bear a α-quaternary stereocenter in generally good to high yields with excellent enantioselectivities. In comparison to the previous method for the construction of tertiary and quaternary stereocenters via carbene gem-difunctionalization reactions, this reaction features an unprecedented gem-dialkylation process via sequential installation of two C-C bonds on the carbene center in one reaction, providing an essential complement to the asymmetric construction of all-carbon quaternary stereocenters using common and readily available starting materials.

Superelectrophilic-Initiated C-H Functionalization at the ß-Position of Thiophenes: A One-Pot Synthesis of trans-Stereospecific Saddle-Shaped Cyclic Compounds.

Superelectrophilic-initiated direct C-H functionalization of thiophenes at the ß-position was developed. A series of trans-stereospecific [2,1-a]-IF-thiophene-fused cyclic compounds (4) with saddle-shaped structure were prepared in 17-30% yields through a one-pot superelectrophilic Friedel-Crafts reaction of dihydroindenofluorene with thiophene derivatives. From the crystal packing analyses of 4a, its skeleton shows both strong intermolecular π-π stacking and C-H···π stacking. Furthermore, the ring-dependent photophysical properties of 4 were confirmed by UV-vis absorption and photoluminescence spectroscopy as well as through the study of their fluorescence quantum yield.

Paclitaxel-induced myocarditis presenting as new-onset heart failure.

Myocarditis with systolic dysfunction is not typically associated with paclitaxel use. Here, we present a case of paclitaxel-induced myocarditis with systolic dysfunction developing after two cycles of carboplatin/paclitaxel in a woman with uterine papillary serous carcinoma and no cardiac risk factors. Myocarditis was diagnosed by cardiac MRI. The management of paclitaxel-induced myocarditis includes intravenous diuresis and initiation of heart failure with reduced ejection fraction guideline-directed medical therapy. Cessation of paclitaxel is also recommended in these patients.

Catalytic 4-exo-dig carbocyclization for the construction of furan-fused cyclobutanones and synthetic applications.

Cyclobutanone is a strained motif with broad applications, while direct assembly of the aromatic ring fused cyclobutanones beyond benzocyclobutenone (BCB) skeletons remains challenging. Herein, we report a Rh-catalyzed formal [3+2] annulation of diazo group tethered alkynes involving a 4-exo-dig carbocyclization process, providing a straightforward access to furan-fused cyclobutanones. DFT calculations disclose that, by comparison to the competitive 5-endo-dig process, 4-exo-dig carbocyclization is mainly due to lower angle strain of the key sp-hybridized vinyl cationic transition state in the cyclization step. Using less reactive catalysts Rh2(carboxylate)4 is critical for high selectivity, which is explained as catalyst-substrate hydrogen bonding interaction. This method is proved successful to direct access previously inaccessible and unknown furan-fused cyclobutanone scaffolds, which can participate in a variety of post-functionalization reactions as versatile synthetic blocks. In addition, preliminary antitumor activity study of these products indicates that some molecules exhibite significant anticancer potency against different human cancer cell lines.

Enantioselective assembly of 3,3-disubstituted succinimides via three-component reaction of vinyl diazosuccinimides with alcohols and imines.

An enantioselective three-component reaction of vinyl diazosuccinimdes with alcohols and imines has been realized by a cooperative catalysis of Rh2(OAc)4 and a chiral phosphoric acid, leading to chiral 3,3-disubstituted succinimides in good to high yields with high to excellent enantioselectivity. The generated product with an alkenyl species could be converted to the chiral tricyclic structure under mild conditions.

Retailer perspectives on sugar-sweetened beverage taxes in the California Bay Area.

The sugar-sweetened beverage (SSB) industry has claimed that food and beverage retailers are opposed to SSB taxes. In 2018 and 2019, we formally evaluated retailers' perceptions of SSB taxes using semi-structured interviews (including open- and closed-ended questions) with 103 randomly selected retailers (50 corner and liquor stores; 28 chain convenience, drug, and mass-merchandise stores; 18 chain supermarkets and discount supermarkets; and 7 independent supermarkets) across 3 cities with SSB taxes (Berkeley, Oakland, and San Francisco); interviews occurred in 2018 and 2019 (approximately 3 years, 1 year and 6 months post tax-implementation, respectively). A majority of both small and large retailers reported the tax had only a minimal effect on their business (70%). About half of retailers believed that other cities should adopt SSB taxes (53%), and were supportive of a statewide SSB tax (53%), noting it would level the playing field and better support health in their communities. Retailers' responses did not differ based on neighborhood income, and only 2 responses differed significantly between large and small retailers. Only 2 of 103 retailers reported raising the price of a non-beverage product in response to the tax, specifically raising the price of snack foods of low nutritional quality and alcoholic beverages. A majority of retailers in 3 California cities with SSB taxes have no concerns regarding the tax, endorse the health goals of SSB taxes and support statewide expansion of SSB tax policies.