Reaction of vinylmagnesium bromide with hexacyclo[10.2.1.02,11.04,9.04,14.09,13]pentadeca-5,7-diene-3,10-dione: Transannular hemiketal formation

Reaction between vinylmagnesium bromide and the cage dione leads to attack of only one equivalent of Grignard and intramolecular nucleophilic attack on the second ketone. The product compound crystallizes in the monoclinic space group, P2₁/a, witha=9.509(1),b=11.071(2),c=12.492(4) Å, =104.32(2)°, andZ=4.     

Structure of 1-(2′-tosyloxyethoxy)-8-tosyloxy-9,10-anthraquinone

The title compound crystallizes in the monoclinic space group, P2₁/c;a=12.938(1),b=11.041(1),c=19.285(2) Å, =104.314(8)°,Z=4. Refinement based on 1660 unique observed reflections converged toR=0.054. The anthraquinone moiety is distorted due to intramolecular steric hindrance from the tosylate groups.     

Finite element error bounds for a curve shrinking with prescribed normal contact to a fixed boundary

We approximate the evolution of a curve subject to motion bycurvature by linear finite elements. The curve evolves insidea given domain and meets orthogonally. We derive optimal boundsfor the error with respect to the L²- and H¹-norms and presentsome computed examples.     

Heterocyclic lithium amides as chiral ligands for an enantioselective hydroxyalkylation with n-BuLi

Chiral heterocyclic structures based on 3-aminopyrrolidines (3APs), 3-aminotetrahydrothiophens (3ATTs), and 3-aminotetrahydrofurans (3ATFs) have been synthesized. The corresponding lithium amides have been evaluated as chiral ligands in the condensation of n-BuLi on o-tolualdehyde. The returned levels of induction were in the 46-80% ee range. The cheap and easily prepared 3ATFLi's turned out to be also the best ligands, giving access to the expected R or S alcohols in a same 80% level of induction at -78 degrees C in THF. In all cases, the sense of induction depends on the absolute configuration of C(8) on the 3-amino appendage. A general concept is proposed to rationalize the process of induction in the presence of organolithium species.     

Chiral Lithium Amides: Tuning Asymmetric Synthesis on the Basis of Structural Parameters

An overview on the structural arrangements adopted by Chiral Lithium Amides (CLAs), alone or in mixed complexes, is presented. These species are important reagents for asymmetric synthesis and understanding their organization is essential to improve their design and the reaction conditions.     

One-Pot Synthesis of Cage-Functionalized,Ketal-Containing Crown Ethers

Acid-catalyzed reaction of pentacyclo[5.4.0.0^2,6.0^3,10.0^5.9]undecane-8,11-dione (1) with penta(ethylene glycol) produced two cage-functionalized, ketal-containing crown ethers, i.e., 2 and 3, in low yield. The structure of 2 was established unequivocally by direct methods. Alkali metal picrate extraction data obtained for 2 and for a structurally related model compound, i.e., 18-crown-6,indicate that 2 is an inefficient alkali metal picrate extracting agent.     

5‐Chloro‐3‐methylthio‐1,2,4‐thiadiazol‐2‐ium chlorides as useful synthetic precursors to a variety of 6aλ4‐thiapentalene systems

Title salts 3 were easily obtained by treatment of formimidoyl isothiocyanates 1 with a twofold excess of methanesulfenyl chloride. They showed interesting chemical behavior toward several nitrogen and carbon nucleophiles. Substitution reactions with isothioureas and acetamide in the presence of triethylamine gave the 1H, 6H‐6aλ⁴‐thia‐1,3,4,6‐tetraazapentalenes 7 and 6H‐6aλ⁴‐thia‐1‐oxa‐3,4,6‐triazapentalene 9 , respectively. Addition of p‐toluidine furnished the 5‐imino‐thiadiazole derivatives 10 , which reacted further with diverse heterocumulenes to yield the corresponding thiatriaza‐ and tetraazapentalene species 11 . The N,N′‐bis(1,2,4‐thiadiazol‐5‐ylidene)diaminobenzenes 13 were also prepared and reacted with phenyl isothiocyanate. Two stable rotational isomers were separated for the 1,2‐phenylene product 14b . Other π‐hypervalent sulfur compounds 16 were synthesized under similar conditions from salts 3 and methyl cyanoacetate or dimethyl malonate. The structural assignments were discussed on the basis of IR and NMR spectroscopic data and received additional support from X‐ray analysis of substrate 16a . © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:95–105, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10106     

Synthesis,Structure–Activity Relationships,and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity.