Improvement of water-solubility of biarylcarboxylic acid peroxisome proliferator-activated receptor (PPAR) δ-selective partial agonists by disruption of molecular planarity/symmetry.

To elucidate the molecular basis of peroxisome proliferator-activated receptor (PPAR) δ partial agonism, X-ray crystal structures of complexes of the PPARδ ligand-binding site with partial agonists are required. Unfortunately, reported PPARδ partial agonists, biphenylcarboxylic acids 1 and 2, possess insufficient aqueous solubility to allow such crystals to be obtained. To improve the aqueous solubility of 1 and 2, substituents were introduced at the 2-position of the biaryl moiety, focusing on disruption of molecular planarity and symmetry.

Azulenocyanine: a new family of phthalocyanines with intense near-IR absorption.

Azulenocyanine, having four azulene units fused to a tetraazaporphyrin skeleton, is a structural isomer of naphthalocyanine. We synthesized the first example of an azulenocyanine from 1,3-di-tert-butyl-5,6-dicyanoazulene. The macrocycle exhibits broad absorption over the visible and near-IR regions far beyond 1000 nm.

Lithium cadmate-mediated deprotonative metalation of anisole: experimental and computational study.

Lithium cadmates bearing different ligands were compared with efficient (TMP)(3)CdLi (TMP = 2,2,6,6-tetramethylpiperidino) for their ability to deprotometalate anisole. The generated arylcadmates were evidenced using I(2). The results show that it is possible to replace only one of the TMP (with a piperidino, a diisopropylamino, a butyl, or a sec-butyl) without important yield drop.

beta-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor agonists: improvement of solubility by disruption of molecular planarity.

The physiological role of aryl hydrocarbon receptor (AhR) is not yet fully understood, and investigation is hampered by the limited solubility of reported AhR ligands in aqueous media. To achieve improved solubility, we focused on our previous finding that planarity-disruption of molecules leads to less efficient crystal packing and greater aqueous solubility. Here, we describe chemical modification of an AhR agonist, beta-naphthoflavone, focusing on planarity-disruption.

Deprotonative metalation of functionalized aromatics using mixed lithium-cadmium, lithium-indium, and lithium-zinc species.

In situ mixtures of CdCl(2)TMEDA (0.5 equiv; TMEDA = N,N,N',N'-tetramethylethylenediamine) or InCl(3) (0.33 equiv) with [Li(tmp)] (tmp = 2,2,6,6-tetramethylpiperidino; 1.

Deprotonative cadmation of functionalized aromatics.

This communication describes the deproto-metalation of a large range of aromatics including heterocycles using a newly developed lithium-cadmium base; the reaction proceeds at room temperature with an excellent chemoselectivity and efficiency, and proved to be regioselective in most cases.

Development of highly chemoselective bulky zincate complex, tBu4ZnLi2: design, structure, and practical applications in small-/macromolecular synthesis.

We present full details of the unique reactivities of the newly developed dianion-type bulky zincate, dilithium tetra-tert-butylzincate (tBu(4)ZnLi(2)). With this reagent, halogen-zinc exchange reaction of variously functionalized haloaromatics and anionic polymerization of N-isopropylacrylamide (NIPAm)/styrene with excellent chemoselectivity were realized. Halogen-zinc exchange reaction followed by electrophilic trapping with propargyl bromide provided a convenient route to functionalized phenylallenes, particularly those with electrophilic functional groups (such as cyano, amide and halogens).

Deprotonative metalation of five-membered aromatic heterocycles using mixed lithium-zinc species.

Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.

Silylmetalation of alkenes.

Silylmetalation of alkenes is challenging due to the low reactivity of the substrates. In contrast, carbometalation of alkenes has been realized through several innovative methods, including activation of the reagent and the substrate. A similar approach could be applicable to silylmetalation of alkenes, and we have recently developed a bimetal activation method using zincate complexes for this purpose.

Regiocontrolled intramolecular cyclizations of carboxylic acids to carbon-carbon triple bonds promoted by acid or base catalyst.

We systematically investigated, for the first time, the relationship between regioselectivity and acid/base effects in the cyclization reactions between carboxylic acids and carbon-carbon triple bonds. We found novel acid- and base-promoted cyclizations to selectively give isocoumarin or pyran-2(2H)-one and phthalide or furan-2(5H)-one skeletons, respectively, and established a catalytic version of regioselective heterocyclic ring synthesis. Density functional theory calculations and application to a short route to thunberginol A were also described.