Helvetica Chimica Acta最新文献

Guaiane sesquiterpenes are an important class of biologically active natural products. Several oxygenated bicyclic but also tricyclic derivatives show unprecedented olfactory activity with great importance in perfumery. Their in vivo syntheses are largely controlled by the intrinsic selectivities of terpene synthases and only a few rearrangements of their hydroazulene skeletons were reported, mostly resulting into terpenoids with decalin motives. Using α-guaiene and bulnesene, complex rearrangements into novel tri and tetracyclic terpenoids are described herein. The cationic rearrangement mechanisms of their formation based on subsequent 1,2-H and alkyl shifts promoted by substoichiometric amounts of ethylaluminum dichloride.

Umifenovir is a broad-spectrum antiviral agent used to treat influenza in China and Russia, and it has been studied as an antiviral agent for the treatment of coronavirus disease 2019 (COVID-19). We have previously reported the synthesis of novel umifenovir analogues and their biological evaluation with a focus on their inhibitory activity against the binding of the spike glycoprotein (S-protein) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the angiotensin-converting enzyme 2 (ACE2) receptor; however, no strong inhibitory activity was observed from these analogues. In the present study, an additional set of umifenovir analogues was synthesized with replacement of the substituents at the 2-, 3-, and 4-positions of the indole, and a cell-based assay using SARS-CoV-2 (B.1.1) was performed to examine the antiviral activity of the analogues. We found that one of the newly synthesized umifenovir analogues exhibited antiviral activity and reduced the viral load to 0.06 % as compared to the control when it was assessed in the presence of nafamostat and marimastat, which inhibit cell-surface viral entry. In contrast, when this analogue was evaluated without the addition of nafamostat or marimastat, it exhibited less antiviral activity, suggesting that the umifenovir analogue would exert antiviral activity mainly by inhibiting endosome-mediated viral entry.

Advancing the use of alkali-metal alkoxides as additives to activate organometallic reagents, here we report the synthesis and characterization of a novel potassium zincate [{(PMDETA)KZn(OtBu)Et₂}₂] obtained by co-complexation of equimolar amounts of potassium tert-butoxide, diethyl zinc and the tridentate donor PMDETA (N,N,N’,N’’,N’’-pentamethyldiethylenetriamine). Demonstrating its ability to activate both of the Et groups towards alkyne C−H metalation, this zincate reacts at room temperature with 2 equivalents of phenylacetylene to furnish [(THF)₂KZn(CCPh)₂(OtBu)}₂], whereas, for the homometallic [ZnEt₂(TMEDA)] (TMEDA=N,N,N’,N’-tetramethylethylendiamine) only one Et group is reactive towards the same substrate under the same conditions. Investigations on the reactivity of these complexes to undergo N−H amine metalation using 2, 6-diisopropylphenylamine (NH₂Dipp) and 1,2,3,4-tetrahydroquinoline (THQ(H)) as model substrates revealed that while homometallic [ZnEt₂(TMEDA)] is completely inert towards these amines, heterobimetallic [{(PMDETA)KZn(OtBu)Et₂}₂] reacts through one of its Et groups to form [(THF)₂KZn(OtBu)(Et)(NHDipp)] as well as [(THF)₄K₂Zn(THQ)₄]. The latter is obtained as a side product of ligand redistribution of a putative [(THF)_nKZn(OtBu)(Et)(THQ)] intermediate. An alternative method to access mixed amide/alkoxide potassium zincates is also described by assessing the co-complexation of KOtBu with Zn(HMDS)₂ in the presence of PMDETA which gave [(PMDETA)KZn(HMDS)₂(OtBu)].

The development of water-soluble hosts for the selective recognition of aromatic amino acids is highly desirable and may serve as a tool to facilitate drug discovery and enable fabrication of sensors for point-of-care monitoring in the context of phenylketonuria disease. This paper presents the synthesis and characterization of a water-soluble molecular cleft which is demonstrated to selectively bind aromatic amino acid guests over other amino acids in aqueous medium, favoring ʟ-Trp over ʟ-Phe and ʟ-Tyr by a factor of approximately five. Host/guest-interaction forces were studied by ¹H-NMR titrations complemented by fluorescence titrations and isothermal titration calorimetry. The here presented results provide a starting point for future optimizations in our efforts to selectively identify and quantify individual aromatic amino acids in aqueous medium.

The preparations, photophysical and electrochemical properties of a series of fac-[Re(CO)₃(diimine)Br] complexes are presented. The bipyridine (bpy) based diimine ligands feature symmetrical and asymmetrical 3,3’-diamino-2,2’-bipyridine substitution patterns. Photophysical and electrochemical properties of these complexes are tunable, depending on their organic diimine framework. Introduction of a distal urea bridge via the 3,3’-substitution pattern led to prolonged phosphorescence lifetimes without a significant change in absorbance and phosphorescence emission wavelengths. Reversible electrochemical bipyridine reduction remained largely unchanged by this derivatization.

We herein report a protocol for the asymmetric 1,4-addition of hydantoins to various Michael acceptors by utilizing Cinchona alkaloid-based chiral quaternary ammonium salt catalysts. Various products were obtained with moderate to good enantioselectivities and accompanying computational investigations helped to identify key interactions responsible for the observed selectivity. DFT calculations along with non-covalent interaction plots reveal the presence of numerous stabilizing non-classical hydrogen bonding interactions along with other non-covalent interactions between the chiral quaternary ammonium salt and hydantoin molecule in the C−C bond forming transition states leading to the formation of the products. In addition, a first proof-of-concept for an analogous a-sulfanylation reaction, albeit with poor selectivity, is reported as well.

This review describes applications of radical reactions developed in the authors’ laboratory for the modification of carbohydrates. It focuses on tin-free variation on the Barton-McCombie deoxygenation; on reductive de-iodination; on intermolecular radical additions of xanthates; on allylations and vinylations of xanthates and iodides, with emphasis on allylations using allylic alcohols activated as fluoropyridyl ethers; and, finally, on the synthesis of mercaptosugars.

The incorporation of nitrogen into small molecules is one of the highest-demanded transformations in modern synthetic chemistry. Alkene difunctionalization and aziridination offer desirable approaches to the incorporation of these amino synthons from feedstock precursors. Although amino groups can be added to alkenes following alkene reaction with an initiation reagent, the most desirable approach involves direct addition of the nitrogen group to the alkene, allowing for a range of possible secondary functionalization outcomes. Although many of these strategies have been accomplished through the use of transition metals, the utility of a transition metal-free approach is still at the forefront of synthetic chemistry, both in development and demand. This review aims to present a comprehensive review of the history and current state-of-the-art in the transition metal-free, direct addition of nitrogen to alkenes.