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Antibiotics have been widely used in the medical field as a treatment for infectious diseases, but they are not effective against all Gram-negative bacteria because of their low permeability to the outer membrane. One of the strategies to improve the antibacterial activity of antibiotics is the coadministration of antibiotics and membrane-perturbing antimicrobial peptides for their synergistic effects. However, because of their different pharmacokinetics, their coadministration may not exert expected effects in the clinical stage. Here, we designed various antimicrobial peptide–antibiotic conjugates as a novel approach to improve the antimicrobial activity of antibiotics. Ampicillin was chosen as a model antibiotic with poor outer membrane permeability, and the effects of the chemistry and position of conjugation and the choice of antimicrobial peptides were examined. One of the ampicillin conjugates exhibited significantly improved antimicrobial activity against ampicillin-resistant Gram-negative bacteria without exerting cytotoxicity against human cultured cells, demonstrating that our novel approach is an effective strategy to improve the antimicrobial activity of antibiotics with low outer membrane permeability.

The Zn(OTf)₂-catalyzed domino reaction of enamide-ynamides in the presence of trimethylsilyl cyanide as an external nucleophile to construct spirocyclic indolines was developed. This domino reaction involved cyclization of enamide to ynamide to generate 4', 5'-dihydrospiro[indoline-3, 3'-pyrrol]-1'-ium followed by cyanide addition to produce spiroindolopyrrolidines with good diastereoselectivity.

Total synthesis of phenanthroquinolizidine alkaloid cryptopleurine was achieved in 8 steps from commercially available 2-pyridinecarboxaldehyde and the epoxide derived from methyleugenol. The key intermediate vinyl triflate enables the divergent synthesis of crypto­pleurine derivatives by late-stage installation of various substituents on the C-ring.

We previously reported an intramolecular migrative cyclization of propargylsufones and sulfonylalkynamides giving oxa- and azacycles, respectively. To confirm the postulated reaction mechanism, the reaction was conducted with chiral nucleophiles such as N-heterocyclic carbenes, phosphines, and pyridines, or with sulfinate anions and chiral cations. As expected, migrative cyclization proceeded to give the enantiomerically enriched products. These results strongly support the postulated mechanism and provide the first example of the asymmetric version of this reaction.

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.

The total synthesis of (−)-sigillin A, a highly chlorinated and oxygenated octahydroisocoumarin, is described herein. A hexahydroisocoumarin skeleton was constructed from (R)-4-(trichloromethyl)oxetan-2-one in seven steps. Its unique manganese oxidation provided an enone as the key intermediate of sigillin A. Stereoselective installation of two hydroxy groups and formation of gem-dichloroalkene from the corresponding ketone led to the total synthesis of (−)-sigillin A in a total of 16 steps.

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.