Preparation of antimicrobial calcium phosphate/protamine composite powders with fluoride ions using octacalcium phosphate.

Calcium phosphates are key biomaterials in dental treatment and bone regeneration. Biomaterials must exhibit antibacterial properties to prevent microbial infection in implantation frameworks. Previously, we developed various types of calcium phosphate powders (amorphous calcium phosphate, octacalcium phosphate (OCP), dicalcium phosphate anhydrate, and hydroxyapatite) with adsorbed protamine (which is a protein with antibacterial property) and confirmed their antibacterial property. In this study, as foundational research for the development of novel oral care materials, we synthesized calcium phosphate composite powders from three starting materials: i) OCP, which intercalates organic compounds, ii) protamine, which has antibacterial properties, and iii) F- ion, which promotes the formation of apatite crystals. Through investigating the preparation concentration of the F- ions and their loading into OCP, it was found that more F- ion could be loaded at higher concentrations regardless of the loading method. It was also observed that the higher the preparation concentration, the more the OCP converted to fluorapatite. The synthesized calcium phosphate composite powders were evaluated for biocompatibility through proliferation of MG-63 cells, with none of the powders exhibiting any growth inhibition. Antimicrobial tests showed that the calcium phosphate composite powders synthesized with protamine and F- ion by precipitation had enhanced antimicrobial properties than those synthesized by protamine adsorption. Thus, the calcium phosphate composite powder prepared from OCP, protamine, and F- ion forms the basis for promising antimicrobial biomaterials. Graphical abstract.

Construction of Tricyclic Nitrogen Heterocycles by a Gold(I)-Catalyzed Cascade Cyclization of Allenynes and Application to Polycyclic π-Electron Systems.

A novel approach to the direct construction of tricyclic nitrogen heterocycles based on gold-catalyzed cascade cyclization of aminoallenynes is described. The expected biscyclization reaction of hydroxyisobutyryl-protected aminoallenynes was efficiently promoted by a catalytic amount of BrettPhosAuNTf2 in the presence of iPrOH to produce 1,2-dihydrobenzo[cd]indole derivatives in good yields. When the reaction was combined with Friedel-Crafts acylation or palladium-catalyzed N-arylation, the resulting tricyclic products were efficiently converted into nitrogen-containing polycyclic aromatic compounds (N-PACs) with highly conjugated π-electron systems. A newly obtained hexacyclic indolium salt showed characteristic concentration-dependent absorption and emission properties.

11-Step Total Synthesis of Teleocidins B-1-B-4.

A unified and modular approach to the teleocidin B family of natural products is presented that proceeds in 11 steps and features an array of interesting strategies and methods. Indolactam V, the known biosynthetic precursor to this family, was accessed through electrochemical amination, Cu-mediated aziridine opening, and a remarkable base-induced macrolactamization. Guided by a desire to minimize concession steps, the tactical combination of C-H borylation and a Sigman-Heck transform enabled the convergent, stereocontrolled synthesis of the teleocidins.

Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines.

Herein, we describe a new catalytic approach to accessing aromatic amines from an abundant feedstock, namely phenols. The most reliable catalytic method for converting phenols to aromatic amines uses an activating group, such as a trifluoromethane sulfonyl group. However, this activating group is eliminated as a leaving group during the amination process, resulting in significant waste. Our nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including a formyl group, are compatible. A bisphosphine ligand immobilized on a polystyrene support (PS-DPPBz) is key to the success of this reaction, generating a catalytic species that is significantly more active than simple nonsupported variants.

N-Heterocyclic Carbene Catalyzed Concerted Nucleophilic Aromatic Substitution of Aryl Fluorides Bearing α,ß-Unsaturated Amides.

Concerted nucleophilic aromatic substitution (CSN Ar) has emerged as a powerful mechanistic manifold, in which nucleophilic aromatic substitution can proceed in one step without the need to form a Meisenheimer intermediate. However, all of the CSN Ar reactions reported thus far require a stoichiometric strong base or activating reagent, and no catalytic variants have yet been reported. Herein, we report an N-heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of acrylamides that contain a 2-fluorophenyl group on the nitrogen through a CSN Ar reaction. By using this catalytic method, it is possible to synthesize an array of quinolin-2-one derivatives, which are common structural motifs in pharmaceuticals and organic materials. DFT calculations unambiguously revealed that this reaction proceeds through the concerted nucleophilic aromatic substitution of aryl fluorides, in which a stereoelectronic σ (Cipso -Cß )→ σ*(Cipso -F) interaction critically contributes to the stabilization of the transition state for the cyclization.

C-O Activation by a Rhodium Bis(N-Heterocyclic Carbene) Catalyst: Aryl Carbamates as Arylating Reagents in Directed C-H Arylation.

Despite recent progress in the catalytic transformation of inert phenol derivatives as alternatives to aryl halides and triflates, attempts at the cross-coupling of inert phenol derivatives with the C-H bonds of arenes have met with limited success. Herein, we report the rhodium-catalyzed cross-coupling of aryl carbamates with arenes bearing a convertible directing group. The key to success is the use of an in situ generated rhodium bis(N-heterocyclic carbene) species as the catalyst, which can promote activation of the inert C(sp2 )-O bond in aryl carbamates.

Nickel-Catalyzed Electrophilic Amination of the Biphenylene C-C σ-Bond.

A nickel-catalyzed three-component carboamination of the biphenylene C-C σ-bond has been developed. Arylboronates and hydroxylamine derivatives work as carbon nucleophiles and nitrogen electrophiles, respectively, and the corresponding difunctionalized ring-opening products are obtained in good yields. The arylboronate nucleophile can be replaced with B2pin2 (boron nucleophile) and H-Si(OMe)3 (hydride nucleophile), thus allowing for the aminoboration and hydroamination of the biphenylene C-C σ-bond under similar nickel catalysis.

Pd-catalysed C-H alkynylation of benzophospholes.

A palladium-catalysed C2-H alkynylation of benzophospholes with alkynyl bromides has been developed to afford the corresponding phosphole-alkyne conjugations in good to high yields. The C-C triple bond as well as terminal alkyne C-H bond in the obtained products is a good synthetic handle for further manipulations, thus giving the versatile π-conjugated benzophosphole derivatives. The optoelectronic properties of the newly synthesized conjugated benzophospholes are also described.

Direct Synthesis of Benzoselenophene and Benzothiophene Derivatives from 1,1-Diarylethenes and Biaryls by Chalcogen Cation-Mediated Successive Bond Formation.

A Tf2O-mediated sequential C-Se bond-forming reaction of 1,1-diarylethenes and biaryls with methaneselenic acid has been developed. Upon demethylation workup with ethanolamine, the corresponding benzoselenophene derivatives are obtained directly. The related synthesis of benzothiophene derivatives with sodium methanesulfinate is also possible with the unique assistance of the ball milling technique. The active species is considered to be a highly electrophilic chalcogen cation, which enables successive bond formation even at room temperature.

Single-carbon atom transfer to α,ß-unsaturated amides from N-heterocyclic carbenes.

Single-carbon atom transfer reactions are lacking in organic synthesis, partly because of the absence of atomic carbon sources under standard solution-phase conditions. We report here that N-heterocyclic carbenes can serve as atomic carbon donors through the loss of a 1,2-diimine moiety. This strategy is applicable to single-carbon atom transfer to α,ß-unsaturated amides, which can be converted into homologated γ-lactams through the formation of four single bonds to one carbon center in one operation.

Late-stage modification of π-electron systems based on asymmetric oxidation of a medium-sized sulfur-containing ring.

The asymmetric oxidation of a sulfur-containing nine-membered heterocycle was achieved for the late-stage introduction of chirality to the substituents of π-electron systems. The oxidation of the sulfur atom considerably influenced the phase-transition behaviour and crystallinity of the resulting π-electron systems.

N-Heterocyclic Carbene-Catalyzed Truce-Smiles Rearrangement of N-Arylacrylamides via the Cleavage of Unactivated C(aryl)-N Bonds.

We report on the N-heterocyclic carbene (NHC)-catalyzed Truce-Smiles rearrangement of aniline derivatives, in which an unactivated C(aryl)-N bond is cleaved, leading to the formation of a new C(aryl)-C bond. The key to the success of this reaction is the utilization of a highly nucleophilic NHC, which enables the formation of a highly nucleophilic ylide intermediate that is generated from an α,ß-unsaturated amide.

Rhodium-Catalyzed C-O Bond Alkynylation of Aryl Carbamates with Propargyl Alcohols.

The rhodium-catalyzed alkynylation of aryl carbamates with propargyl alcohols is described. This methodology can provide aryl acetylenes from aryl carbamates via C-O bond activation. The use of propargyl alcohols as alkynylating agents allows the use of a variety of functional groups that are incompatible with organometallic nucleophiles. This reaction also serves to broaden the utility of a carbamate moiety as a convertible ortho directing group.