Yasuyuki Ura

Self-Assembling Sequence-Adaptive Peptide Nucleic Acids

Adaptable DNA Analogs The defining feature of DNA as a genetic blueprint is its capacity for self-replication. In the cell, however, the replication process requires the assistance of multiple elaborate enzymes. How then at the origin of life could DNA or its precursor replicate before enzymes were present? Ura et al. (p. 73, published online 11 June) have achieved the long-sought goal of preparing a synthetic DNA analog that can dynamically adapt its sequence in free solution. Their analog (as yet only studied in relatively short, 20-unit oligomers) replaces DNAs sugar and phosphate backbone by a peptide strand in which cysteines reversibly bind the conventional DNA bases through thioester tethers. These strands can pair with complementary sequences of true DNA and furthermore swap one tethered base for another if different DNA templating strands are added to the solution in succession. A synthetic DNA analog can dynamically adapt its sequence in response to changing templates. Several classes of nucleic acid analogs have been reported, but no synthetic informational polymer has yet proven responsive to selection pressures under enzyme-free conditions. Here, we introduce an oligomer family that efficiently self-assembles by means of reversible covalent anchoring of nucleobase recognition units onto simple oligo-dipeptide backbones [thioester peptide nucleic acids (tPNAs)] and undergoes dynamic sequence modification in response to changing templates in solution. The oligomers specifically self-pair with complementary tPNA strands and cross-pair with RNA and DNA in Watson-Crick fashion. Thus, tPNA combines base-pairing interactions with the side-chain functionalities of typical peptides and proteins. These characteristics might prove advantageous for the design or selection of catalytic constructs or biomaterials that are capable of dynamic sequence repair and adaptation.

Cu(I) Catalyzed or Promoted Metallacycle Transfer of Zirconacycles to Stannacycles.

Abstract Zirconacyclopentadienes, zirconacyclopentenes and zirconacyclopentanes were readily transferred to the corresponding stannacycles in the presence of a catalytic or a stoichiometric amount of CuCl. Without CuCl, the above transfer did not proceed at all or proceeded very slowly. A convenient one-pot procedure for the preparation of spiro stannacyclopentadiene compounds was also developed with CuCl.

Facile Insertion of Carbon Dioxide into Cu2(μ-H) Dinuclear Units Supported by Tetraphosphine Ligands

Reactions of meso-bis[(diphenylphosphinomethyl)phenylphosphino]methane (dpmppm) with Cu(I) species in the presence of NaBH4 afforded di- and tetranuclear copper hydride complexes, [Cu2(μ-H)(μ-dpmppm)2]X (1) and [Cu4(μ-H)2(μ4-H)(μ-dpmppm)2]X (2) (X=BF4, PF6). Complex 1 undergoes facile insertion of CO2 (1 atm) at room temperature, leading to a formate-bridged dicopper complex [Cu2(μ-HCOO)(dpmppm)2]X (3). The experimental and DFT theoretical studies clearly demonstrate that CO2 insertion into the Cu2(μ-H) unit occurred with the flexible dicopper platform. Complex 2 also undergoes CO2 insertion to give a formate-bridged complex, [Cu4(μ-HCOO)3(dpmppm)2]X, during which the square Cu4 framework opened up to a linear tetranuclear chain.

A highly stereoselective synthesis of the C10–C31 (BCDEF ring) portion of pinnatoxin A

Abstract An efficient, highly stereoselective synthesis of the C10–C31 (BCDEF ring) portion of pinnatoxin A has been achieved utilizing tandem double hemiketal formation/intramolecular hetero-Michael addition to construct the 6,5,6-dispiroketal (BCD ring) system and subsequent intramolecular ketalization to form the 5,6-bicycloketal (EF ring) system as key steps.

Tiara-like Octanuclear Palladium(II) and Platinum(II) Thiolates and Their Inclusion Complexes with Dihalo- or Iodoalkanes

A tiara-like octanuclear palladium thiolate complex, [Pd(μ-SCH2CO2Me)2]8, that has a toroidal structure was synthesized via reactions of either PdCl2 with methyl thioglycolate/N,N-diisopropylethylamine (DIEA) (conventional method) or [PdCl2(MeCN)2] with m-C6H4(CMe2SCH2CO2Me)2 (alternative method). In the latter method, the tiara-like complex formed via the corresponding SCS-pincer complex and/or 1:1 PdCl2 and ligand complexes. With respect to the platinum analogues, the alternative method efficiently produced the tiara-like octanuclear complex [Pt(μ-SCH2CO2Me)2]8 in high purity. Small molecules, such as CH2Cl2, ClCH2CH2Cl, CH2Br2, and CH3I, were accommodated in the inner voids of the tiara rings to form 1:1 inclusion complexes. These complexes are stabilized not only by weak CH···X hydrogen bonds (X = Cl or Br) between the methylene protons of four or eight axially positioned methoxycarbonylmethyl groups on the tiara rings and the halogen atoms of the guest molecules but also by weak coordination of the halogen atoms to the transition-metal atoms.

Dynamic polythioesters via ring-opening polymerization of 1,4-thiazine-2,5-diones.

We describe the preparation and characterization of polythioesters composed of alternating alpha-amino acid and alpha-thioglycolic acid residues that undergo dynamic constitutional exchange under mild conditions. The polymers are assembled via reversible ring-opening polymerizations of 1,4-thiazine-2,5-diones and related monomers in solution-phase conditions that do not require the use of transition metal catalysts. Because 1,4-thiazine-2,5-diones can be derived in part from alpha-amino acids, a variety of side chain functionalized monomers in optically pure forms could readily be accessed. In addition, the resulting polythioesters have the potential for intra- and inter-chain hydrogen bonding, which is known to impart materials properties to other previously studied polyamides. The studies reported here could be useful in advancing a new class of biodegradable polymers and furthermore suggest that dynamic constitutional exchange could be exploited to modify many known synthetic and natural polythioesters.

Allene formation by coupling of propargylic ethers with olefins via β-alkoxide elimination of zirconacycle intermediates

Abstract A zirconoceneethylene complex reacted with propargylic ethers to give allene derivatives in good yields via β-alkoxide elimination. Deuterolysis of the reaction mixture revealed that the final product after elimination still had a zirconiumcarbon bond. Coupling of styrene and propargylic ethers was mediated by Cp 2 ZrBu 2 (Negishi reagent) to give phenethyl allene derivatives. β-Alkoxide elimination from zirconacyclopentadienes bearing two α-CH 2 OMe groups was also observed. One CH 2 OMe group was easily eliminated. Elimination of the second CH 2 OMe group was dependent on its structure.

A Fluxional Cu8H6 Cluster Supported by Bis(diphenylphosphino)methane and its Facile Reaction with CO2

A copper hydride cluster [Cu8 (μ-H)6 (μ-dppm)5 ](PF6 )2 (dppm=bis(diphenylphosphino)methane) was prepared from reaction of [CuH(PPh3 )]6 with dppm in the presence of [Cu(CH3 CN)4 ]PF6 and exhibited fluxional behaviors in solution where the hydrides and the phosphines are scrambling around the trans-bicapped octahedral Cu8 framework. The Cu8 H6 complex showed facile reactivity with CO2 (1 atm, RT) to afford a tricopper complex, [Cu3 (μ-H)(μ-O2 CH)(μ-dppm)3 ]PF6 , which could be developed to unprecedented hydrosilylation of CO2 catalyzed by multinuclear CuH species under mild conditions.

Allene formation by the reaction of olefins with propargyl silyl ethers mediated by a zirconocene complex

Abstract Ethylene and styrene derivatives reacted with various propargylic ethers in the presence of zirconocene(II) to afford allenic products in high yields. The reaction proceeded via formation of zirconacyclopentenes by selective coupling of an olefin and a propargylic ether, which was followed by β-elimination of the siloxy group. Deuterolysis confirmed that the final product had a zirconium-carbon bond.

Rhodium‐Catalyzed Decarbonylative Coupling Reactions of Diphenylketene with Alkenes

Ketenes are reactive and useful synthetic intermediates in traditional organic chemistry. Much attention has been focused on ketene-coordinated transition metal complexes with the aim of developing new catalytic reactions that use ketenes as a starting material. In organometallic chemistry, ketenes have often been generated in situ by the coupling of the carbene and carbon monoxide ligands on the metal, which has been implicated as a key step in several useful synthetic reactions, such as benzannulations, ketene–imine or ketene–alkene cycloadditions, and electrophilic substitution reactions. In sharp contrast, the reverse reaction, cleavage of a ketene ligand to carbene and CO ligands on a single metal center, is extremely rare, and, in general, metal–CO complexes and alkenes, probably derived from the dimerization of carbene ligands, are formed. Based on our research on rhodium-, ruthenium-, and palladium-catalyzed coupling reactions of heterocumulenic compounds, such as isocyanates and ketenes, with alkynes, we have developed novel rhodium-catalyzed decarbonylative coupling reactions of diphenylketene with alkenes. The reaction of diphenylketene 1 a with 2-norbornene 2 a gave the corresponding substituted cyclopropane, 3,3-diphenyltricyclo[3.2.1.0 ]octane (3 a), whereas the reaction with electron-deficient alkenes, 2 b–d, gave linear coupling products 4 a–c, by decarbonylation. In these reactions, diphenylketene could be safely used as an efficient diphenyl carbene source. The reaction of 1 a (3.0 mmol) with 2 a (1.0 mmol) in the presence of [{RhCl(CO)2}2] catalyst (0.050 mmol) in toluene at 120 8C for 12 h under an argon atmosphere gave 3 a in 81 % yield, together with the formation of a stoichiometric amount of CO [0.90 mmol; Eq. (1)] .