Trifluoromethylated aromatic compounds are the substances of considerable interest in various industrial fields. The high lipophilicity, strong electron-withdrawing ability, and charasteristic size of trifluoromethyl group are key influences in biologically active molecules. Due to these attractive properties, the benzotrifluoride structural motifs have been widely employed in the design of pharmaceuticals, agrochemicals, dyes, liquid crystals, and polymers. Therefore, the development of highly efficient methodologies for aromatic trifluoromethylation is of significant importance for wide fields of science and technology. Recently, a great deal of attention has been paid to transition metal-catalyzed protocols to introduce trifluoromethyl groups into aromatic rings selectively. This review outlines the successful examples on catalytic aromatic trifluoromethylation, such as electrophilic and radical trifluoromethylation of aromatic compounds, cross-coupling of aryl halides with CF3Cu reagents, cross-coupling of aromatic halides with nucleophilic trifluoromethylation agents catalyzed by copper and palladium complexes, and catalytic oxidative cross-coupling to give trifluoromethylated aromatics effectively.
This review describes the development of a new class of chiral secondary phosphine oxide preligands: Amino acid-derived P-chiral diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric reactions. The Pd-DIAPHOX catalyst system was successfully applied to enantioselective construction of quaternary stereocenters through Pd-catalyzed asymmetric allylic alkylation with β-keto esters as prochiral nucleophiles, asymmetric allylic substitutions with nitromethane, asymmetric allylic amination with various substrates, and enantioselective synthesis of axially chiral allenes. Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were also examined using structurally optimized DIAPHOX preligands, and the corresponding branched products were obtained in a highly regio- and enantioselective manner. Furthermore, the developed processes were successfully applied to the enantioselective synthesis of biologically active compounds.
The structure of guadinomines, new inhibitors of a bacterial Type III secretion system (T3SS) isolated from the cultured broths of Streptomyces sp. K01-0509. The property has been traced to the novel guadinomines A to D, and three of them have been identified as being selective inhibitors of T3SS. In the process of isolation, a new compound, guadinomic acid was detected, occurring as a biosynthetic intermediate. The T3SS is expressed by many Gram-negative pathogens, where it helps deliver effector proteins into the host cell during the infection process. Original structural analysis was elucidated by spectroscopic studies including various NMR experiments. Guadinomines A to D consist of a carbamoylated cyclic guanidinyl moiety, an alkyl chain moiety and an dipeptide moiety in common, while guadinomic acid is a smaller molecule including a carbamoylated cyclic guanidinyl moiety. However, the relative and absolute configurations of these compounds remained to be determined, except for the peptide moiety. Herein, we report the isolation, the total assignment of the configurations of guadinomic acid, guadinomines B and C2, through the first asymmetric total synthesis of these natural products.
This paper focuses on the synthesis of new aromatic compounds by thermal, photochemical, or oxidative cleavage reaction of the corresponding precursors. The precursor-methods are useful for the derivatization of the non-soluble aromatic compounds. We have applied retro Diels-Alder reactions for the preparation of new π-expanded porphyrinoid compounds such as tribenzotriphyrin(2.1.1), tetrabenzoporphycene, dodecasubstituted porphycene, tetraanthraporphyin, butadiyne-linked tetrabenzoporphyrin dimer, and so on. We have investigated the photocleavage synthesis of pentacenes from the corresponding α-diketone precursors. This photoreaction enabled us to prepare 1,4,8,11-tetrasubstituted pentacene. The synthesis of new pentacene derivatives with electron-withdrawing substituents at 6,13-positions by oxidative cleavage reaction will be also reported.
Cytosine methylation at the 5-position in DNA has been implicated in a epigenetic regulation of genetic information and diseases including cancer, and therefore it has become important to identify the methylation status of a specified cytosine residue in DNA to obtain a molecular insight into the biological function of cytosine methylation. To discriminate between cytosine and 5-methylcytosine (mC), we investigated a photochemical one-electron oxidation at 5-methylcytosine in DNA, using oligodeoxynucleotides (ODN) possessing a 2-methyl-1,4-naphthoquinone (NQ) chromophore. Photoirradiation and subsequent hot piperidine treatment of the duplex consisting of the NQ-tethered ODN and its complementary strand bearing mC led to oxidative cleavage at the mC residue, which is located at the front of the NQ chromophore. Detailed mechanistic study revealed that rapid deprotonation of the mC radical cation generated by NQ-photosensitization and subsequent addition of molecular oxygen to generate alkali labile oxidized form would lead to cleavage at the original mC site. We also designed an efficient fluorometric detection system of DNA methylation based on a combination of photooxidative DNA cleavage reaction with NQ chromophore and invasive cleavage reaction with Human Flap endonuclease-I. Enzymatic treatment of a mixture of photochemically fragmented target ODNs at mC and hairpin-like probe oligomer possessing a fluorophore and a quencher resulted in a dramatic enhancement of fluorescence. Thus, the presented systems would be a highly sensitive protocol for the identification of methylation status in DNA.
Umpolung chemistry has been the focus of research on organic synthesis due to its usefulness and unusual reactivity. Above all, umpolung of enamine property enables the formation of highly substituted carbon-carbon bonds and installation of aryl groups on sp3 carbon atoms, which are difficult to realize by normal enolate chemistry. This short review describes recent reports of the carbon-carbon bond formation by umpolung reactions of enamine derivatives.