Electrophilic aromatic substitution of 3‐alkoxy‐6‐alkyl‐2‐cyano‐4,5,6a,11‐tetraazabenzo[a]fluorene with orthoesters

Fused tetracycles, 6‐alkyl‐3‐alkoxy‐2‐cyano‐4,5,6a,11‐tetraazabenzo[a]fluorene derivatives ( 5a , b , c , d , e , f ), are synthesized from 2‐alkoxy‐5‐(benzimidazol‐2‐ylidene)‐3‐cyano‐6‐imino‐5,6‐dihydro‐pyridines ( 4b , c ), and when refluxed in ethyl orthoacetate or ethyl orthopropionate, the elecrophilic aromatic substitution occurs at the ortho position of the cyanopyridine ring in the fused tetracycles ( 5b , c , e , f ) to afford 6‐alkyl‐3‐alkoxy‐2‐cyano‐1‐ethyl‐4,5,6a,11‐tetraazabenzo[a]fluorenes( 6b , c , e , f ).     

2-nitrophenyl isocyanide as a versatile convertible isocyanide: rapid access to a fused gamma-lactam beta-lactone bicycle

2-Nitrophenyl isocyanide is introduced as a convertible isocyanide with demonstration of its feasibility and applicability in an efficient synthesis of the fused gamma-lactam beta-lactone bicycle of proteasome inhibitor omuralide. Starting from a linear keto acid precursor, the fused gamma-lactam beta-lactone bicycle was prepared in four steps by a sequential biscyclization strategy; a stereocontrolled Ugi reaction and the concomitant direct beta-lactonization following the formation of an N-acylbenzotriazole intermediate. The N-acylbenzotriazole is amenable to intra- or intermolecular attack from a variety of nucleophiles with a catalytic amount of base to form the pyroglutamic acid derivatives.     

Synthesis of the common propellane core structure of the hasubanan alkaloids

The racemic synthesis of the common propellane core structure found in various hasubanan alkaloids is reported. The successful completion hinged upon the stereocontrolled construction of the cis-substituted heterobicycle as a precursor for the intramolecular Dieckmann condensation. A novel strategy is introduced for the facile hydrolysis of a sterically demanding carboxamide under a mild condition. The 2-nitroanilide obtained by the Goldberg arylation of a carboxamide with 2-iodonitrobenzene was readily converted to the corresponding ester derivative by way of N-acylbenzotriazole. We expect that the reported synthetic route will allow the synthesis of a series of hasubanan alkaloids starting from the correspondingly functionalized 2-tetralone derivatives.     

Enantiodifferentiating photoisomerization of cyclooctene included and sensitized by aroyl-beta-cyclodextrins: a critical enantioselectivity control by substituents

A series of 6-O-benzoyl-beta-cyclodextrins (CDs) with methyl, methoxy, methoxycarbonyl, and bromo substituent(s) at the ortho-, meta-, and/or para-position(s) were synthesized as chiral sensitizing hosts for the use in supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to its chiral (E)-isomer (1E). The complex stability constants (K(S)) of the modified beta-CDs with 1Z in aqueous methanol solutions were highly sensitive to the substituent(s) introduced to the benzoate moiety, and the log K(S) values decreased linearly with slightly different slopes with increasing methanol content. The enantiomeric excess (ee) of 1E obtained upon photosensitization with these hosts was a critical function of the size and position of the substituent, varying from almost zero to 46% ee. This indicates that even an apparently small structural difference between methyl and methoxy can critically affect the enantiodifferentiating photoisomerization of a guest included in the chiral cavity, probably through manipulation of both the orientation of ground-state 1Z and the subsequent rotational relaxation of excited 1Z inside the chiral cavity.     

One-Step Synthesis of Cyclobutene-Annulated Fullerenes through a Cascade Reaction

The physicochemical properties of fullerene-based materials typically vary depending on the type and mode of addition of functional groups; therefore, developing fullerene derivatives with novel structures is imperative for further progress in materials science. In this study, we develop an efficient one-step strategy for synthesizing cyclobutene-annulated fullerene derivatives (cyclobutenofullerenes) and characterize their electronic properties. Despite the steric strain, cyclobutenofullerenes can be easily prepared via a one-step reaction of C₆₀ with a secondary propargylic phosphate. Structural analysis of the reaction intermediates suggests that the cascade reaction proceeds through a formal [2+2] cycloaddition of C₆₀ with an allene, caused by the 1,3-migration of the propargylic phosphate, followed by an additional 1,3-migration and the subsequent 1,2-elimination of the phosphodiester moiety.     

An M2L4 Molecular Capsule with a Redox Switchable Polyradical Shell

Preparation of molecular nanostructures with polyradical frameworks remains a significant challenge because of the limited synthetic accessibility which is entirely different from that of neutral and ionic ones. Herein we report the quantitative formation of a new M₂L₄ molecular capsule from metal ions and dihydrophenazine‐based ligands. The capsule has a spherical nanocavity (ca. 1 nm in diameter) enclosed by eight redox‐active, dihydrophenazine panels. Electrochemical oxidation of the capsule leads to the generation of multiple radical cations on the shell framework. Moreover, a stable tetra(radical cation) capsule can be reversibly obtained by chemical as well as electrochemical oxidation.     

Controlled diastereoselectivity at the alkene-geometry through selective encapsulation: E-Z photoisomerization of oxazolidinone-functionalized enecarbamates within hydrophobic nano-cavities

Photoisomerization of encapsulated Z-enecarbamates within the hydrophobic chiral cavities of gamma-CD showed higher diastereoselectivities in the photoproducts than those obtained in solution. The selective encapsulation of the enecarbamates and the following isomerization process are both diastereoselectively controlled by gamma-CD.     

Physicochemical characterization of tamoxifen citrate pseudopolymorphs, methanolate and ethanolate

Two novel pseudopolymorphs, methanolate and ethanolate of tamoxifen [(Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine]citrate, were prepared in addition to forms A and B reported previously. Their crystalline forms were identified and characterized by powder and single crystal X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, scanning electron microscopy and diffuse reflectance infrared Fourier-transform spectroscopy, and their physicochemical stability was also evaluated. The results of single crystal X-ray analysis and thermogravimetric analysis of methanolate and ethanolate suggested that the stoichiometry of tamoxifen citrate : methanol and tamoxifen citrate : ethanol could be composed of a 1 : 1 molecular ratio for both solvates. The results of physicochemical stability evaluations at 75 and 97% RH at 40 and 60 degrees C indicated that the metastable form A was quite stable for at least 2 months even under severe storage conditions, whereas methanolate immediately transformed to a crystalline mixture of forms A and B, and subsequently changed to the stable form B.