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The highly regio- and enantioselective intramolecular cyclopropanation reactions of naphthyl diazoacetamides have been reported herein. In the presence of a Ru(II)-Pheox catalyst, chiral and stable norcaradiene derivatives were obtained from the corresponding diazoacetamides

Resilin, an insect structural protein, has excellent flexibility, photocrosslinking properties, and temperature responsiveness. Recombinant resilin-like proteins (RLPs) can be fabricated into three-dimensional (3D) structures for use as cell culture substrates and highly elastic materials. A simplified, high-yielding production process for RLPs is required for their widespread application. This study proposes a simple production process combining extracellular expression using Brevibacillus choshinensis (B. choshinensis) and rapid column-free purification. Extracellular production was tested using four representative signal peptides; B. choshinensis was found to efficiently secrete Rec1, an RLP derived from Drosophila melanogaster, regardless of the type of signal peptide. However, it was suggested that Rec1 is altered by an increase in the pH of the culture medium associated with prolonged incubation. Production in a jar fermentor with controllable pH yielded 530 mg Rec1 per liter of culture medium, which is superior to productivity using other hosts. The secreted Rec1 was purified from the culture supernatant via (NH

Organometallic complexes [Ru-Colefin(sp2)-Ru(II)-Pheox 2a-2d] containing a Ru-Colefin(sp2) bond have been prepared from unsaturated chiral oxazoline derivatives and evaluated for asymmetric cyclopropanation reactions. The corresponding optically active cyclopropanes were obtained with high yields and high stereoselectivities (≥99/

The first catalytic asymmetric cyclopropanation of diazo oxime ethers with olefins was developed. In the presence of a Ru(II)-Pheox catalyst, various optically active cyclopropyl oxime derivatives were obtained in high yields (up to 99%) with high enantioselectivities (up to 98% ee). Furthermore, optically active cyclopropyl oxime ethers could be successfully converted into the corresponding cyclopropyl methylamine derivatives via metal hydride and Grignard reagent mediated Beckmann rearrangement, which are potential candidates for the assessment of biological and pharmaceutical activities.

Sphingomyelinase C (SMC) hydrolyzes sphingomyelin to ceramide and phosphocholine. Prokaryotic SMCs share sequence homology with mammalian SMCs that have enzymatic pH optima at neutral pH. SMC from the nonpathogenic prokaryote Streptomyces griseocarneus shows notable enzymatic features such as higher optimum pH and thermostability than other prokaryotic SMCs. Determination of the three-dimensional structure of S. griseocarneus-SMC (Sg-SMC) and comparison with other SMC structures represents a promising strategy to elucidate the unique enzymatic features of Sg-SMC on a structural basis. Therefore, we determined the crystal structure of Sg-SMC at 2.0 A resolution by X-ray crystallography. Comparison of the Sg-SMC structure with three other structurally known SMCs from Listeria ivanovii, Bacillus cereus, and Staphylococcus aureus indicated that Sg-SMC is more diverse in sequence and that structural differences in the main chain between these SMCs are primarily located on the molecular surface distant from the active site. Comparison of the surface area of the four SMCs revealed that Sg-SMC has the most compact structure, which may contribute to the enhanced thermostability of Sg-SMC. Regarding the hydrogen bond network in the active site of Sg-SMC, a basic amino acid, Arg278, is involved, whereas the corresponding residue in other SMCs (Ser or Asn) does not form hydrogen bonds with metal-coordinating water molecules. Hydrogen bond formation between Arg278 and a Mg2+ ion-coordinating water molecule may be responsible for the higher optimal pH of Sg-SMC compared to that of other SMCs.

A reusable and highly enantioselective catalyst for the intramolecular cyclopropanation of various diazo ester and Weinreb amide derivatives was developed. The reactions catalyzed by a water-soluble Ru(II)-Amm-Pheox catalyst proceeded smoothly at room temperature, affording the corresponding bicyclic cyclopropane ring-fused lactones and lactams in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). After screening of various catalysts, the Ru(II)-Amm-Pheox complex having an ammonium group proved to be crucial for the intramolecular cyclopropanation reaction in a water/ether biphasic medium. The water-soluble catalyst could be reused at least six times with little loss in yield and enantioselectivity.

This work reports the first efficient enantioselective intramolecular Buchner reaction of diazoacetamides. The Ru(ii)-Pheox catalyst was shown to be highly efficient in this transformation in terms of both the regio- and enantioselectivity (up to 99% ee) giving the desired products in quantitative yield.

Organometallic complexes [Ru-C

We established a highly enantioselective Si-H insertion reaction to construct chiral centers at the carbon and silicon atoms, using a Ru(ii)-pheox catalyst. The catalytic asymmetric Si-H insertion reaction of α-methyl-α-diazoesters proceeded smoothly with excellent stereoinduction at both the neighboring carbon and silicon atoms (up to 99% yield and 99% ee).

Optically active spirocyclopropyloxindole derivatives were efficiently synthesized from diazooxindoles and olefins in the presence of a Ru(II)-Pheox catalyst. Among a series of Ru(II)-Pheox catalysts, Ru(II)-Pheox 6e was determined to be the best catalyst for spirocyclopropanation reactions of diazooxindoles with various olefins in high yields (up to 98%) with high diastereoselectivities (up to trans:cis = >99:1

Computational chemical analysis of Ru(II)-Pheox-catalyzed highly enantioselective intramolecular cyclopropanation reactions was performed using density functional theory (DFT). In this study, cyclopropane ring-fused γ-lactones, which are 5.8 kcal/mol more stable than the corresponding minor enantiomer, are obtained as the major product. The results of the calculations suggest that the enantioselectivity of the Ru(II)-Pheox-catalyzed intramolecular cyclopropanation reaction is affected by the energy differences between the starting structures 5l and 5i. The reaction pathway was found to be a stepwise mechanism that proceeds through the formation of a metallacyclobutane intermediate. This is the first example of a computational chemical analysis of enantioselective control in an intramolecular carbene-transfer reaction using C1 -symmetric catalysts.

The enantioselective formation of α-aryloxy-β-keto esters is described for the first time. Lewis acid catalyzed enantioselective chlorination of β-keto esters and subsequent SN 2 reactions with phenols yielded α-aryloxy-β-keto esters with up to 96% ee. Favorskii rearrangement of α-chloro-β-keto esters was also found to give 1,2-diesters with slightly reduced enantiopurity.

Resorcin[4]arene (resorcinol cyclic tetramer, abbreviated as RCT) or pyrogallol[4]arene (pyrogallol cyclic tetramer, PCT) form host–guest 1:1 complexes with DL -pipecolinic acid ( DL -pipeH), RCT· DL -pipeH·EtOH·8H2O (1), PCT DL -pipeH·EtOH·4H2O (2), and PCT· DL -pipeH·3H2O (3), whose crystal structures have been determined. In each complex, the pipeH ligand is incorporated into the bowl-shaped cavity of the RCT or PCT host molecules through C–H⋯π interactions between alkyl protons of the piperidine ring of pipeH and π-rings of RCT or PCT, forming an [(RCT/PCT)·pipeH] structural fragment. In 1 and 3, two [(RCT/PCT) pipeH] fragments self-associate across an inversion center to form a guest-mediated, obliquely declined dimeric structure [(RCT/PCT)· L -pipeH· D -pipeH (RCT/PCT)]. In 2, each PCT-capped pipeH ligand bridges to two adjacent PCT molecules to form guest-mediated, optically-discrete helical polymers [PCT· L -pipeH]n or [PCT· D -pipeH]n. An 1H NMR experiment shows that the complexation through C–H⋯π interaction between the piperidine ring of pipeH and π-rings of RCT or PCT occurs also in solution, with the binding constants of 9.7 ± 0.6 M−1 for RCT and 26.5 ± 1.5 M−1 for PCT. These complexes provide a synthetic model for the recognition of the pipecolinyl-ring moiety, a key constituent of immunosuppressant drugs such as FK506, FK520 or rapamycin, by their binding proteins through C–H⋯π interaction.

Metal ions play a key role in nucleic acid structure and activity. The elucidation of factors/rules that govern the binding of metal ions is therefore an essential step for the better understanding of nucleic acid functions. In this review, we deal with stereospecific intra-molecular interligand interactions as such a factor, involving hydrogen-bonding, electrostatic interaction, and steric constraints, especially focusing on their significance as a factor that could affect base-specific metal bonding to adenine and guanine bases in the solid state.

Single crystal X-ray analysis of the complex formed between pyrogallo[4]arene ( 1 ) and phosphocholine (PCh), [Ca(H 2 O) 3 ( 1 ) 2 ]·(PCh − ) 2 ·2EtOH·5H 2 O, a model compound that mimics PCh–receptor recognition in biological systems, has shown that PCh is incorporated into the bowl-shaped cavity of 1 through cation–π interactions between the quaternary cationic trimethylammonium group of PCh and π-rings of 1 . The hepta-coordinated [Ca(H 2 O) 3 ] 2+ ion is directly bound to two molecules of 1 through phenolic oxygens to form a dimeric molecule of 1 , [ 1 {Ca(H 2 O) 3 } 1 ] 2+ . Conformational data of PCh and its derivatives observed in known crystal structures are compiled, focusing on the conformation about the C–C bond in the P–O–C–C–N + backbone with a reemphasis that the usually observed gauche conformation could be stabilized by an intramolecular N + –C(methyl group)–H⋯O hydrogen bonding.

The glycine betaine (betaine), interacts with several types of proteins with diverse structures in vivo, and in the contact regions, the aromatic rings of protein residues are frequently found beside the trimethylammonium group of betaine, implying the importance of the cation−π interactions in recognition of this molecule. The crystal structures determined by X-ray crystallography of the complexes of betaine and C-ethyl-pyrogallol[4]arene (pyrogallol cyclic tetramer: PCT) and betaine and C-ethyl-resorcin[4]arene (resorcinol cyclic tetramer: RCT) mimic the conformations of betaine and protein complexes and show that the clathrate conformations are retained by the cation−π interactions. The difference of the conformation feature of betaine in the Protein Data Bank and in the Cambridge Structural Database was found by chance during the research and analyzed with the torsion angles.

Highly enantioselective chlorination of β-oxo esters and subsequent stereospecific substitution of tertiary chlorides are described. Enantioselective chlorination of β-keto esters and malonates was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline ligand 2 to yield the desired α-chlorinated products with high enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting chlorides proceeded smoothly to afford a variety of chiral molecules such as α-amino, α-alkylthio, and α-fluoro esters, without loss of enantiopurity. The results of X-ray crystallographic analysis proved that Walden inversion occurs at the chlorinated tertiary carbon center. These results supported the fact that the substitution proceeds via an S(N)2 mechanism.

Crystal structures of two vancomycin complexes with phosphate and N-acetyl–D-Ala (AcDA) were determined. Each complex involves two crystallographically independent vancomycin molecules (V1 and V2) ...

Reaction of 1,4,7,10-tetraazacyclododecane (cyclen) and Cu(ClO4)2·6H2O with nucleobases (adenine, hypoxanthine, xanthine, theophylline, cytosine, or uracil) under alkaline conditions gave four ternary cyclen–metal–nucleobase complexes, [Cu(cyclen)(adeninato)]·ClO4·2H2O (1), [{Cu(cyclen)}2(hypoxanthinato)]·(ClO4)3 (2), [Cu(cyclen)(theophyllinato)]3·(ClO4)3·2H2O (3), and [Cu(cyclen)(xanthinato)]·(0.7ClO4)·(0.3ClO4)·3H2O·(0.5H2O)3 (4), whose crystal structures were determined by X-ray diffraction. In the adenine complex 1, a cyclen-capped square–pyramidal Cu2+ ion binds to an adeninato ligand through N(9) with the formation of an intramolecular interligand hydrogen bond between the secondary amino nitrogen of cyclen and N(3) of the base. In the hypoxanthine complex 2, two cyclen-capped Cu2+ ions bind to a hypoxanthinato ligand, one through N(7) with the formation of an intramolecular N(cyclen)–H···O(6) hydrogen bond and the other through N(9) to form an intramolecular N(cyclen)–H···N(3) hydrogen bond. Similarly, in both the theophylline complex 3 and the xanthine complex 4, each cyclen-capped Cu2+ ion binds to a theophyllinato or xanthinato ligand through N(7) with the formation of an intramolecular N(cyclen)–H···O(6) hydrogen bond. However, unlike in 2, steric constraints between amino group(s) of cyclen and the methyl group at N(3) of theophylline in 3 or the proton attached to N(9) of xanthine in 4 preclude the metal bonding to N(9) in 3 or N(3) in 4. The significance of intramolecular interligand interaction as a factor that affects metal-binding site(s) on nucleobases is emphasized.

Reaction between nucleobases (adenine, hypoxanthine, cytosine, and uracil), tris(2-aminoethyl)amine (tren) and M(ClO4)2 (M2+ = Zn2+, Cd2+, Ni2+ or Cu2+) under pH 8–9 gave eight ternary tren-metal ion-nucleobase complexes, among which seven crystal structures, [Zn(tren)(adeninato)] · ClO4 (1), [Cd(tren)(adeninato)] · ClO4 (2), [Ni(tren)(adeninato)(ClO4)] (3), [Zn(tren)(hypoxanthinato)] · ClO4 · H2O (4), [{Cd(tren)}2(hypoxanthinato)] · (ClO4)3 · 0.5 H2O (5), [Ni(tren)(uracilato)(H2O)] · ClO4 · (0.5H2O)2 (7), and [Cu(tren)(uracilato)] · ClO4 · 0.5H2O (8) were determined by X-ray diffraction. In each of the adenine complexes with Zn2+ (1), Cd2+ (2), and Ni2+ (3), among which 1 and 2 are isostructural to each other, a tren-capped metal ion binds to an adeninato ligand through N(9) with the formation of an intramolecular interligand hydrogen bond between the amino nitrogen of tren and N(3) of the base. In the hypoxanthine complexes 4 and 5, a tren-capped Zn2+ ion in 4 binds to a hypoxanthinato ligand through N(9) with the formation of an intramolecular N(tren)–H⋯N(3) hydrogen bond, while in 5 two tren-capped Cd2+ ions bind to a hypoxanthinato ligand, one through N(7) with the formation of an intramolecular N(tren)–H⋯O(6) hydrogen bond and the other through N(9) to form an intramolecular N(tren)–H⋯N(3) hydrogen bond. In each of the uracil complexes with Ni2+ (7) and Cu2+ (8), a tren-capped metal ion binds to an uracilato ligand through N(1) with the formation of an intracomplex O(aqua)–H⋯O(2) hydrogen bond in 7 or an intramolecular N(tren)–H⋯O(2) hydrogen bond in 8. Tren-capped metal ion-bonded nucleobases act as building blocks for the assembly of supramolecular structures, by versatile hydrogen bonding and/or stacking abilities of nucleobases. The significance of intramolecular interligand interaction as a factor that affects metal-binding site(s) on nucleobases is emphasized.

The crystal structures of three vancomycin complexes with two vancomycin-sensitive cell-wall precursor analogs (diacetyl-Lys-D-Ala-D-Ala and acetyl-D-Ala-D-Ala) and a vancomycin-resistant cell-wall precursor analog (diacetyl-Lys-D-Ala-D-lactate) were determined at atomic resolutions of 1.80 A, 1.07 A, and 0.93 A, respectively. These structures not only reconfirm the "back-to-back" dimerization of vancomycin monomers and the ligand-binding scheme proposed by previous experiments but also show important structural features of strategies for the generation of new glycopeptide antibiotics. These structural features involve a water-mediated antibiotic-ligand interaction and supramolecular structures such as "side-by-side" arranged dimer-to-dimer structures, in addition to ligand-mediated and "face-to-face" arranged dimer-to-dimer structures. In the diacetyl-Lys-D-Ala-D-lactate complex, the interatomic O...O distance between the carbonyl oxygen of the fourth residue of the antibiotic backbone and the ester oxygen of the D-lactate moiety of the ligand is clearly longer than the corresponding N-H...O hydrogen-bonding distance observed in the two other complexes due to electrostatic repulsion. In addition, two neighboring hydrogen bonds are concomitantly lengthened. These observations provide, at least in part, a molecular basis for the reduced antibacterial activity of vancomycin toward vancomycin-resistant bacteria with cell-wall precursors terminating in -D-Ala-D-lactate.

Reaction between xanthine, tris(2-aminoethyl)amine (tren) and M(ClO 4 ) 2 (M = Zn 2+ , Cd 2+ , Ni 2+ or Cu 2+ ) under alkaline conditions gave five ternary tren–metal ion–xanthine complexes, among which crystal structures of [Zn(tren)(H 2 xan)] · ClO 4 · H 2 O ( 1 ), [Cd(tren)(H 2 xan)] · ClO 4 · H 2 O ( 2 ), [Ni(tren)(H 2 xan)(H 2 O)] · ClO 4 · H 2 O ( 3 ), and [Cu 2 {(μ-Hxan)Cu(tren)} 2 (μ-Hxan) 2 (H 2 O) 2 ] · 10H 2 O ( 4 ) (H 3 xan = neutral xanthine) were determined by X-ray diffraction. In the Zn 2+ ( 1 ) and Cd 2+ ( 2 ) complexes, which are isostructural to each other, the tren-capped metal ion binds to xanthine through N(7) with the formation of an intramolecular interligand hydrogen bond between the amino nitrogen of tren and O(6) of the base. The Ni 2+ complex ( 3 ) involves the metal bonding to N(7) of the base with the formation of two intramolecular hydrogen bonds between O(6) of the base and the amino group of tren and the aqua ligand. The tetranuclear Cu 2+ complex ( 4 ) forms a paddle-wheel type of centrosymmetrical dicopper tetraxanthinate structure, where the two copper ions are bridged by four xanthine ligands through N(3)/N(9) chelation and, in addition, two among the four xanthine ligands are metalated each by the tren-capped copper ion through N(7) with the formation of an intramolecular hydrogen bond between the amino group of tren and O(6) of the base. The significance of intramolecular interligand interaction as a factor that affects site-specific metal bonding is emphasized. A review of metal bonding properties of so far reported xanthine–metal complexes is given.

The enantioselective formation of α-aryloxy-β-keto esters is described for the first time. Lewis acid catalyzed enantioselective chlorination of β-keto esters and subsequent SN 2 reactions with phenols yielded α-aryloxy-β-keto esters with up to 96% ee. Favorskii rearrangement of α-chloro-β-keto esters was also found to give 1,2-diesters with slightly reduced enantiopurity.

Reaction of tris(2-aminoethyl)amine (tren) and Cu(ClO 4 ) 2 , Ni(ClO 4 ) 2 , or Ni(NO 3 ) 2 with purine nucleobases (adenine, 9-ethylguanine, and hypoxanthine) gave five ternary tren–metal ion–nucleobase complexes, [Ni(tren)(adeninato)(ClO 4 )] · adenine ( 1 ), [Cu(tren)(9-ethylguanine)] · (ClO 4 ) 2 ( 2 ), [{Ni(tren)(H 2 O)} 2 (hypoxanthinato)] · (ClO 4 ) 3 · 1.5H 2 O ( 3 ), [Ni(tren)(hypoxanthinato)(H 2 O)] · ClO 4 · 2H 2 O ( 4 ), and [{Ni(tren)(H 2 O)} 2 (hypoxanthinato)] 2 · (NO 3 ) 6 · 4.5H 2 O ( 5 ), where 1 and 4 were prepared under pH 8–9 while 2 , 3 , and 5 were under pH 6–7, and their crystal structures were determined by X-ray diffraction. In the adenine complex 1 , the tren-capped metal ion binds to the base through N(9) with the formation of an intramolecular interligand hydrogen bond between the amino group of tren and N(3) of the base, and the 9-ethylguanine complex 2 involves the metal bonding to N(7) of the base with the formation of an intramolecular hydrogen bond between the amino group of tren and O(6) of the base. In the hypoxanthine complexes 3 and 5 , the metal ions bind to N(7) in addition to N(9), forming three intramolecular hydrogen bonds, two involving O(6) with the amino nitrogen of tren and the aqua ligand and one between the aqua ligand and N(3) of the base, whereas the hypoxanthine complex 4 involves the metal bonding solely to N(9) with the formation of an intramolecular hydrogen bond between the aqua ligand and N(3) of the base, where N(7) as well as N(1) are hemi-protonated. The absence of the metal–N(7) bonding for adenine in 1 while the metal bonding to N(7) specific for guanine derivatives in 2 , 3 and 5 are rationalized in terms of interligand interactions.

X-ray analyses of two calix[4]pyrogallolarene complexes with DL-proline have shown that they form host–guest-like 1:1 complexes in which the pyrrolidine ring of proline is incorporated into the bow...

Resorcin[4]arene and tetramethylated resorcin[4]arene form complexes with L-carnitine, whose crystal structures were determined. Each complex contains two carnitine ligands in the asymmetric unit, ...

Metal ions play a key role in nucleic acid structure and activity. The elucidation of factors/rules that govern the binding of metal ions is therefore an essential step for the better understanding of nucleic acid functions. In this review, we deal with stereospecific intra-molecular interligand interactions as such a factor, involving hydrogen-bonding, electrostatic interaction, and steric constraints, especially focusing on their significance as a factor that could affect base-specific metal bonding to adenine and guanine bases in the solid state.

Tetramethylated resorcin[4]arene self-assembles to form molecular capsules incorporating a tetraethylammonium ion within the cavity through cation-π interactions. Two "head-to-head" arranged substructures are staggered with each other so as to participate in mcthyl-hydroxy van der Waals interactions between pairing substructures. The tetraethylammonium ion is oriented in a vertical or horizontal fashion.

When tetraethylresorcin[4]arene is crystallized from dioxane, it forms a “head-to-head” arranged self-dimer directly connected by non-conventional O–H···π interaction. The resorcinarene molecule ad...

The reaction occurs in the presence of the new ligands (I) affording α-chlorinated products with high enantioselectivity.

Diels—Alder reactions of β-fluoromethylacrylates in the presence of a Lewis acid activated chiral oxazaborolidine catalyst provide access to fluoromethylated cyclohexenes with very high enantioselectivity.

Highly enantioselective Diels–Alder reactions of β-fluoromethylacrylates were carried out in the presence of a Lewis acid activated chiral oxazaborolidine catalyst. These reactions yielded fluoromethylated cyclohexenes, including trifluoromethyl-, difluoromethyl-, and monofluoromethyl cyclohexenes, as nearly pure enantiomers. The resulting fluoromethyl cyclohexenes were converted into potential synthetic intermediates for bioactive compounds.

Tetramethylated resorcin[4]arene (MRCT) forms ‘head-to-head’ arranged self-dimers incorporating neutral guest molecules methanol, ethanol, and imidazole within the cavity, with the MRCT:guest compo...