Rhodium-Catalyzed Double Dearomatization of 1,2,3-Triazole-Isoxazole Dyads: Synthesis of Nonfused 1-1,3-Diazepines.

A double dearomatization of dyads consisting of 1-sulfonyl-1,2,3-triazoles and 3-aryl-5-methoxyisoxazoles was applied for the efficient synthesis of nonfused 1-1,3-diazepines. The plausible mechanism of the cascade reaction includes transformation of the 1,2,3-triazole to rhodium azavinyl carbene, the -selective hydride shift to form the 1-azabuta-1,3-diene moiety, rhodium-catalyzed ring contraction of the isoxazole to azirine, and pseudopericyclic four-atom ring expansion of the azirine. The synthetic utility and antiproliferative activity of the 1,3-diazepines obtained have been demonstrated.

Metal-(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple-Negative Breast Cancer.

Invited for the cover of this issue are Tatiyana Serebryanskaya, Mikhail Kinzhalov and co-workers at St. Petersburg State University, the Research Institute for Physical Chemical Problems, Belarusian State University, Togliatti State University and Blokhin National Medical Research Center of Oncology. The image depicts the shield of Pallas Athena with the structure of a palladium carbene complex that protects against triple-negative breast cancer.

Facile synthesis of diiodoheteroindenes and understanding their Sonogashira cross-coupling selectivity for the construction of unsymmetrical enediynes.

Electrophile-promoted cyclizations of functionalized alkynes offer a useful tool for constructing halogen-substituted heterocycles primed for further derivatization. Preinstallation of an iodo-substituent at the alkyne prior to iodo-cyclization opens access to di-iodinated heterocyclic precursors for the preparation of unsymmetrical heterocycle-fused enediynes. This general approach was used to prepare 2,3-diiodobenzothiophene, 2,3-diiodoindole, and 2,3-diiodobenzofuran, a useful family of substrates for systematic studies of the role of heteroatoms on the regioselectivity of cross-coupling reactions.

Acridine-Isoxazole and Acridine-Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity.

Easy-to-handle -hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine-azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320-420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition.

Metal-(Acyclic Diaminocarbene) Complexes Demonstrate Nanomolar Antiproliferative Activity against Triple-Negative Breast Cancer.

Hydrolytically stable Pd and Pt complexes supported by acyclic diaminocarbene ligands represent a novel class of structural organometallic anticancer agents exhibiting nanomolar antiproliferative activity in a panel of cancer cell lines (IC 0.07-0.81 μM) and up to 300-fold selectivity for cancer cells over normal primary fibroblasts.

Xanthone-1,2,4-triazine and Acridone-1,2,4-triazine Conjugates: Synthesis and Anticancer Activity.

A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (, , , , and ) displayed good in vitro antiproliferative activities against these cancer cell lines.

3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors.

The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2.

Selective and Reversible 1,3-Dipolar Cycloaddition of 2-(2-Oxoindoline-3-ylidene)acetates with Nitrones in the Synthesis of Functionalized Spiroisoxazolidines.

The 1,3-dipolar cycloaddition of 2-(2-oxoindoline-3-ylidene)acetates with functionalized aldo- and ketonitrones proceeds with good selectivity to provide new highly functionalized 5-spiroisoxazolidines. A characteristic feature of these reactions is reversibility that allows for the control of the diastereoselectivity of cycloaddition. The reduction of obtained adducts using zinc powder in acetic acid leads to 1,3-aminoalcohols or spirolactones.

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold.

Formation of unusual unsymmetrical dimers or/and indenes via Rh(esp)-catalyzed decomposition of 3-diazo-2-arylidenesuccinimides has been investigated. The reaction proceeded under mild conditions, and its result was shown to strongly depend on the nature of the substituents in the diazo substrate. The new reaction provides access to dibenzoazulenodipyrrole and indenopyrrole derivatives in moderate to high yield.

Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells.

A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin-targeting lead molecules with the acylated 4-aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β-aryl-substituted vinylketones by tert-butyl nitrite in the presence of water as a key step. 4-Methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC  = 0.

Rhodium-Catalyzed Synthesis of 2-Aroylpyrimidines via Cascade Heteropolyene Rearrangement.

A one-step synthesis of cytotoxic 2-aroylpyrimidines by the denitrogenative reaction of 1-tosyl-1,2,3-triazoles with isoxazoles under rhodium catalysis has been developed. According to the density functional theory calculations and control experiments, the disclosed reaction proceeds via the rearrangement of an oxadiazatetraene intermediate involving a cascade of intramolecular aza-Diels-Alder and retro-aza-Diels-Alder reactions. The presence of a substituent at C4 of the isoxazole is a prerequisite for the formation of the pyrimidines.

A Hydroxypyrrole Approach to 2,2'-Bi(4-pyrrolin-3-ones) and Pyrrolone-Based α-Amino Esters.

A high yield synthesis of 2-amino-4-pyrrolin-3-ones including 4-pyrrolin-3-one-based amino esters by the NBS- or TfCl-mediated reaction of 3-hydroxypyrroles with amines has been developed. The reaction of 3-hydroxypyrroles with triflyl chloride in the absence of amine affords 2,2'-bi(4-pyrrolin-3-ones) in excellent yields and diastereoselectivity. The relative configuration of stereocenters in these compounds can be changed from (2,2') to (2,2') by the action of NaH in THF, while the reverse stereoisomerization occurs in the presence of 2,5-lutidine in MeCN.

Crystal structures of -[(4-phenyl-thia-zol-2-yl)carbamo-thio-yl]benzamide and -{[4-(4-bromo-phen-yl)thia-zol-2-yl]carbamo-thio-yl}benzamide from synchrotron X-ray diffraction.

The title compounds, CHNOS, (I), and CHBrNOS, (II), are potential active pharmaceutical ingredients. Compound (I) comprises two almost planar fragments. The first is the central (carbamo-thio-yl)amide (r.

Crystal structures of ethyl {2-[4-(4-iso-propyl-phen-yl)thia-zol-2-yl]phen-yl}carbamate and ethyl {2-[4-(3-nitro-phen-yl)thia-zol-2-yl]phen-yl}carbamate.

The title compounds, CHNOS (I) and CHNOS (II), are structural analogs of the alkaloid Thio-sporine B. Both mol-ecules adopt a near-planar V-shaped conformation, which is consolidated by intra-molecular N-H⋯N and C-H⋯O hydrogen bonds. The crystal structure of (I) consists of mlecular stacks along the axis, in which the mol-ecules are linked to each other by π(S)⋯π(C) inter-actions.

2-Bromo-1-[1-(4-bromo-phen-yl)-5-methyl-1H-1,2,3-triazol-4-yl]ethanone.

The asymmetric unit of the title compound, C11H9Br2N3O, contains two crystallographically independent mol-ecules with similar geometries; the Br-C-C=O torsion angles are 1.2 (4) and -2.8 (4)°, and the benzene and triazole rings are inclined o one another by 51.

2-Phenyl-5,6,7,8-tetra-hydro-imidazo[2,1-b][1,3]benzo-thia-zole.

The title compound, C15H14N2S, crystallizes with two independent mol-ecules in the asymmetric unit. The central imidazo[2,1-b][1,3]benzo-thia-zole unit is planar (r.m.

3-Bromo-2-[4-(methyl-sulfan-yl)phen-yl]-5,6,7,8-tetra-hydro-1,3-benzo-thia-zolo[3,2-a]imidazole.

In the title mol-ecule, C16H15BrN2S2, the central imidazo[2,1-b]thia-zole fragment is almost planar (r.m.s.

(Z)-N-[1-(Aziridin-1-yl)-2,2,2-tri-fluoro-ethyl-idene]-4-bromo-aniline.

The title compound, C10H8BrF3N2, crystallizes with two independent mol-ecules in the asymmetric unit, which can be considered as being related by a pseudo-inversion center, so their conformations are different; the corresponding N=C-N-C torsion angles are 54.6 (5) and -50.5 (5)°.

7-Nitro-2-phenyl-imidazo[2,1-b][1,3]benzo-thia-zole.

In the title mol-ecule, C15H9N3O2S, the central imidazo[2,1-b][1,3]benzo-thia-zole heterotricyclic unit is essentially planar (r.m.s.

2-Bromo-4-phenyl-1,3-thia-zole.

In the title mol-ecule, C9H6BrNS, the planes of the 2-bromo-1,3-thia-zole and phenyl rings are inclined at 7.45 (10)° with respect to each other. In the crystal, mol-ecules related by a centre of symmetry are held together via π-π inter-actions, with a short distance of 3.

6-(4-Chloro-phen-yl)-3-methyl-imidazo[2,1-b]thia-zole.

In the title compound, C12H9ClN2S, the imidazo[2,1-b]thia-zole fragment is planar (r.m.s.

2-(Adamantan-1-yl)-N-(6-meth-oxy-1,3-benzo-thia-zol-2-yl)acetamide.

The asymmetric unit of the title compound, C20H24N2O2S, contains two independent mol-ecules having very similar geometries. The main N-(6-meth-oxy-1,3-benzo-thia-zol-2-yl)acetamide moiety adopts an almost planar structure (r.m.

(E)-1,5-Di-phenyl-pent-2-en-4-yn-1-one.

The title compound, C17H12O, has an E conformation about the C=C bond. The C-C C-C torsion angle is 7.7 (2)°, and the mean planes of the phenyl-ethyl-enone [r.