Chromic properties of dibenzo[j,l]fluoranthenes exhibiting different resonance contributions.

Chromic molecules change colour in response to external stimuli and are utilized in applications such as food additive detection, light dimmers, and biological probes. One of the common design strategies for organic chromic molecules is based on changes in the π-conjugation. We have hypothesized that non-alternant polyaromatic hydrocarbon (PAH) skeletons can be used as backbones for chromic molecules. Herein, we synthesized hydroxy-substituted dibenzo[j,l]fluoranthenes, a class of non-alternant PAHs, as novel chromic compounds and evaluated their halochromic properties by UV-vis and fluorescence spectroscopy. Under basic conditions, the 1-hydroxy derivatives show a hyperchromic shift, whereas the 9-hydroxy derivatives show a bathochromic shift and fluorescence although the skeleton of the chromophore is the same. Density functional theory calculations indicated that the different chromic properties are attributed to the differences in their resonance structures.

Structure-ATPase Activity Relationship of Rhodamine Derivatives as Potent Inhibitors of P-Glycoprotein CmABCB1.

Understanding the transport and inhibition mechanisms of substrates by P-glycoprotein (P-gp) is one of the important approaches in addressing multidrug resistance (MDR). In this study, we evaluated a variety of rhodamine derivatives as potential P-gp inhibitors targeting CmABCB1, a P-gp homologue, with a focus on their ATPase activity. Notably, a Q-rhodamine derivative with an o,o'-dimethoxybenzyl ester moiety (RhQ-DMB) demonstrated superior affinity and inhibitory activity, which was further confirmed by a drug susceptibility assay in yeast strains expressing CmABCB1. Results from a tryptophan fluorescence quenching experiment using a CmABCB1 mutant suggested that RhQ-DMB effectively enters and binds to the inner chamber of CmABCB1. These findings underscore the promising potential of RhQ-DMB as a tool for future studies aimed at elucidating the substrate-bound state of CmABCB1.

Intramolecular Ynamide-Benzyne (3+2) Cycloadditions.

We report herein intramolecular (3+2) cycloaddition reactions between ynamides as three-atom components and benzyne. In these intramolecular reactions, the two-bond formation is realized by exploiting benzyne precursors that contain a chlorosilyl group as a linking functionality. This method thus highlights the ambivalent character of the intermediate indolium ylide, which exhibits both nucleophilic and electrophilic properties at its C2 atom.

2-(Chlorodiisopropylsilyl)-6-(trimethylsilyl)phenyl triflate: a modified platform for intramolecular benzyne cycloadditions.

2-(Chlorodiisopropylsilyl)-6-(trimethylsilyl)phenyl triflate serves as an efficient aryne precursor for intramolecular benzyne [4 + 2] or (2 + 2 + 2) cycloadditions. Key features of this precursor are (1) rapid connection of various arynophiles to the precursor via a Si-O bond and (2) generation of aryne under mild conditions using a combination of Cs2CO3 and 18-crown-6.

Oxidative ß-Cleavage of Fused Cyclobutanols Leading to Hydrofuran-Fused Polycyclic Aromatic Compounds.

Treatment of aryl-fused bicyclo[4.2.0]octanols with an oxidant such as phenyliodine diacetate (PIDA) or hypochlorous acid gave dihydrofuran-containing polycyclic aromatic compounds by selective ß-cleavage of the cyclobutanol moiety. Mechanistic studies suggest that the oxygen atom of the hydrofuran ring is incorporated from the hydroxy group of the substrate via intramolecular addition. The oxidative transformation should serve as a new method to prepare functionalized polycyclic aromatic compounds.

Helical Nanographenes Embedded with Contiguous Azulene Units.

The azulene moiety, composed of contiguous pentagonal and heptagonal rings, is a structural defect that alters the electronic, magnetic, and structural properties of graphenes and graphene nanoribbons. However, nanographenes embedded with an azulene cluster have not been widely investigated because these compounds are difficult to synthesize in their pure form. Herein, azulene-embedded nanographenes bearing a unique cove-type edge were synthesized by a novel synthetic protocol. Experimental and theoretical investigations revealed that this cove edge imparts stable helical chirality, unlike normal cove edges. The in-solution self-association behavior and the structural, electronic, and electrochemical properties were also described in detail.

Intramolecular Benzyne-Phenolate [4+2] Cycloadditions.

An intramolecular benzyne-phenolate [4+2] cycloaddition is reported. Benzyne precursors, having vicinal halogen-sulfonate functionalities, linked with a phenol(ate) by various tether groups undergo efficient intramolecular [4+2] cycloaddition by treatment with either Ph3 MgLi or nBuLi for halogen-metal exchange to form various benzobarrelenes.

Synthesis of Polycyclic Spirocarbocycles via Acid-Promoted Ring-Contraction/Dearomative Ring-Closure Cascade of Oxapropellanes.

We report herein the development of an acid-promoted rearrangement of oxa[4.3.2]propellanes to afford polyaromatic-fused spiro[4.5]carbocycles. DFT calculations suggest that the reaction pathway involves generation of a cyclobutyl cation, ring contraction to the cyclopropylcarbinyl cation, and dearomative ring closure by an internal 2-naphthol moiety. The resulting spirocarbocycles are synthetically valuable, as they could be transformed into two different polycyclic aromatic hydrocarbons via skeletal rearrangement. Syntheses of optically pure spirocarbocycles via a central-to-axial-to-central chirality transfer are also described.

Total Syntheses of Allelopathic 4-Oxyprotoilludanes, Melleolides, and Echinocidins.

Stereocontrolled total syntheses of allelopathic 4-oxyprotoilludane sesquiterpenes, melleolide, melleolide F, and echinocidins B and D were achieved. The curved 5/6/4 tricyclic system with an angular hydroxy group was built via three key transformations: (1) Me3Al-catalyzed [2 + 2] cycloaddition of a ketene silyl acetal with a propiolate, (2) reductive ring-opening of a cyclic hemiketal, and (3) the intramolecular Morita-Baylis-Hillman reaction. This synthetic route represents a new and reliable strategy to obtain protoilludanes with several oxy-functional groups.

Synthesis of Functionalized Medium-Sized trans-Cycloalkenes by 4π Electrocyclic Ring Opening/Alkylation Sequence.

Development of a novel synthetic method for medium-sized trans-cycloalkenes (TCAs) is described. Functionalized TCAs are readily prepared from simple cycloalkanones in a few steps, namely, enol silyl ether formation, [2+2] cycloaddition, and domino 4π electrocyclic ring opening/alkylation (conjugate addition). The first example of central-to-planar chirality transfer from enantiomerically enriched cyclobutenes to TCAs is also described.

2-Bromo-6-(chlorodiisopropylsilyl)phenyl tosylate as an efficient platform for intramolecular benzyne-diene [4 + 2] cycloaddition.

An intramolecular benzyne-diene [4 + 2] cycloaddition with broad substrate scope has been realized by using a cleavable silicon tether, allowing access to various polycyclic structures. 2-Bromo-6-(chlorodiisopropylsilyl)phenyl tosylate serves as an efficient platform for (1) rapid attachment of various arynophiles to the benzyne precursor via a Si-O bond and (2) facile generation of benzyne via halogen-metal exchange with Ph3MgLi.

Aryne-based strategy in the total synthesis of naturally occurring polycyclic compounds.

The total syntheses of polycyclic natural products by exploiting an aryne as the key reactive species are reviewed. A short introduction summarizes the basic reactivities of aryne species as well as the methods for its generation. In the main part, early examples and the recent reports (mainly 2012-present) on the use of arynes in multistep syntheses are described.

Synthesis and Properties of Tribenzocarbazoles via an Acid-Promoted Retro (2+2)-Cycloaddition of Azapropellanes.

We describe herein the development of a new method to synthesize tribenzocarbazoles via an acid-promoted retro (2+2)-cycloaddition of azapropellanes, which were prepared by potassium hexamethyldisilazide (KHMDS)-promoted (2+2)-cycloaddition. The tribenzocarbazoles showed strong fluorescence both in solution and the solid state. The structural, electronic, and optical properties of the synthetic tribenzocarbazoles are also described.

First Total Syntheses of Tetracenomycins†C and X.

The first total syntheses of tetracenomycins C and X were achieved, featuring 1) preparation of a hexasubstituted naphthonitrile oxide by successive benzyne cycloadditions and an oxidative ring-opening reaction; 2) a novel ortho-quinone mono-acetal as the A-ring unit; 3) construction of three contiguous stereogenic centers by an asymmetric benzoin cyclization, an isoxazole oxidation, and a stereoselective reduction.

Concise total syntheses of amphidinolides†C and F.

The marine natural products amphidinolide C (1) and F (4) differ in their side chains but share a common macrolide core with a signature 1,4-diketone substructure. This particular motif inspired a synthesis plan predicating a late-stage formation of this non-consonant ("umpoled") pattern by a platinum-catalyzed transannular hydroalkoxylation of a cycloalkyne precursor. This key intermediate was assembled from three building blocks (29, 41 and 47 (or 65)) by Yamaguchi esterification, Stille cross-coupling and a macrocyclization by ring-closing alkyne metathesis (RCAM). This approach illustrates the exquisite alkynophilicity of the catalysts chosen for the RCAM and alkyne hydroalkoxylation steps, which activate triple bonds with remarkable ease but left up to five other π-systems in the respective substrates intact. Interestingly, the inverse chemoselectivity pattern was exploited for the preparation of the tetrahydrofuran building blocks 47 and 65 carrying the different side chains of the two target macrolides. These fragments derive from a common aldehyde precursor 46 formed by an exquisitely alkene-selective cobalt-catalyzed oxidative cyclization of the diunsaturated alcohol 44, which left an adjacent acetylene group untouched. The northern sector 29 was prepared by a two-directional Marshall propargylation strategy, whereas the highly adorned acid subunit 41 derives from D-glutamic acid by an intramolecular oxa-Michael addition and a proline-mediated hydroxyacetone aldol reaction as the key steps; the necessary Me3 Sn-group on the terminus of 41 for use in the Stille coupling was installed via enol triflate 39, which was obtained by selective deprotonation/triflation of the ketone site of the precursor 38 without competing enolization of the ester also present in this particular substrate.

Synthesis of isoxazoles en route to semi-aromatized polyketides: dehydrogenation of benzonitrile oxide-para-quinone acetal cycloadducts.

A variety of highly functionalized polycyclic isoxazoles are prepared by a two-step protocol: (1) 1,3-dipolar cycloaddition of o,o'-disubstituted benzonitrile oxides to para-quinone mono-acetals, then (2) dehydrogenation. The cycloaddition proceeds in a regioselective manner, favouring the formation of the 4-acyl cycloadducts, which are suitable intermediates for the synthesis of semi-aromatized polycyclic targets derived from polyketide type-II biosynthesis.