Fast Protein Modification in the Nanomolar Concentration Range Using an Oxalyl Amide as Latent Thioester.

We show that latent oxalyl thioester surrogates are a powerful means to modify peptides and proteins in highly dilute conditions in purified aqueous media or in mixtures as complex as cell lysates. Designed to be shelf-stable reagents, they can be activated on demand to enable ligation reactions with peptide concentrations as low as a few hundred nM at rates approaching 30 M-1 s-1 .

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue.

A new asymmetric organocatalyzed intramolecular aza-Michael reaction by means of both a chiral auxiliary and a catalyst for stereocontrol is reported for the synthesis of optically active isoindolinones. A selected cinchoninium salt was used as phase-transfer catalyst in combination with a chiral nucleophile, a Michael acceptor and a base to provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists.

Mixed Allyl Rare-Earth Borohydride Complexes: Synthesis, Structure, and Application in (Co-)Polymerization Catalysis of Cyclic Esters.

A series of new trivalent rare-earth allyl-borohydride complexes with the formula [RE(BH4 )2 (C3 H5 )(thf)x ] (RE=Sc (1), x=2; RE=Y (2) and La (3), x=3) were synthesized by reaction of the corresponding rare-earth trisborohydrides [RE(BH4 )3 (thf)x ] with half an equivalent of bis(allyl)magnesium. The complexes were fully characterized by determining their X-ray structure. Similar to their previously described Nd (4) and Sm (5) analogues, these complexes display a monomeric structure with two terminal trihapto BH4 groups, one π-η3 allyl ligand, three THF molecules for complexes 2 and 3, and two THF molecules for complex 1. The catalytic behavior of complexes 1-5 toward the ring-opening polymerization (ROP) of l-lactide (l-LA) and ϵ-caprolactone (ϵ-CL) was assessed. The Nd complex featured the best activity toward l-LA (turnover frequency (TOF)=1300 h-1 ) and the order was Nd>La>Sm>Y>Sc. Complexes 1-3 were found very active for the ROP of ϵ-CL (TOF=166 000 h-1 ), which is in line with the already established exceptionnally high performance of complexes 4 and 5. With both monomers, it was shown that the borohydride moiety was the preferentially initiating group, rather than the allyl one. The random copolymerization of l-LA and ϵ-CL was performed with complexes 1-5, in the absence or in the presence of benzyl alcohol as a chain-transfer agent, affording copolymers with ϵ-caprolactone up to 62 % inserted. The copolymers synthesized display a variety of microstructures, that is, blocky, random, or quasi-alternating.

Gold(I)-Catalysed Asymmetric Hydroamination of Alkenes: A†Silver- and Solvent-Dependent Enantiodivergent Reaction.

In the present study, we report the first silver-dependent enantiodivergent gold-catalysed reaction. The asymmetric intramolecular hydroamination of alkenes catalysed by the combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate can afford both enantiomers of the products by a simple solvent change from toluene to methanol. Such an enantiodivergent reaction is strictly independent of the reaction temperature or of the nature of the catalyst anion and displays the same first-order kinetic rate law with respect to substrate concentration in both solvents. Beyond a simple solvent effect the enantioinversion is controlled by gold-silver chloride adducts which occur only in methanol and allow a dual activation of the reagent. While one single gold atom activates the alkene moiety, the other gold atom forms an oxophilic gold-silver chloride adduct which is likely to interact with the carbamate function. By comparison with toluene, which affords (S)-enantiomer, this proximal and bimetallic activation would allow an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and lead therefore to the (R)-enantiomer.

Selective Hydrosilylation of Esters to Aldehydes Catalysed by Iridium(III) Metallacycles through Trapping of Transient Silyl Cations.

The combination of an iridium(III) metallacycle and 1,3,5-trimethoxybenzene catalyses rapidly and selectively the reduction of esters to aldehydes at room temperature with high yields through hydrosilylation followed by hydrolysis. The ester reduction involves the trapping of transient silyl cations by the 1,3,5-trimethoxybenzene co-catalyst, supposedly by formation of an arenium intermediate whose role was addressed by DFT calculations.

3-Benzyl-1-{[3-(4-chloro-phen-yl)isoxazol-5-yl]meth-yl}-1H-benzimidazol-2(3H)-one.

In the title compound, C24H18ClN3O2, the benzimidazole plane is nearly perpendicular to the phenyl ring and to the isoxazole ring, making dihedral angles of 75.95 (7) and 73.04 (8)°, respectively, but the two residues point in opposite directions with respect to the benzimidazole plane. The dihedral angle between the chloro-phenyl and isoxazole rings is 7.95 (8)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds into inversion dimers.

1-(Prop-2-en-1-yl)-3-{[3-(pyridin-4-yl)-4,5-di-hydro-isoxazol-5-yl]meth-yl}-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.

The fused five- and three six-membered rings of the anthra[1,2-d]imidazole-trione part of the title compound, C27H20N4O4, show two different substituents at the imidazole N atoms, viz. an allyl group and a [3-(pyridin-4-yl)-4,5-di-hydro-isoxazol-5-yl]methyl group. The fused-ring system is approximately planar [r.m.s. deviation = 0.232 (2) Å], but is slightly buckled along the common edge of the two pairs of adjacent rings, with a dihedral angle between them of 11.17 (6)°. The isoxazole ring makes dihedral angles of 27.2 (2) and 12.7 (2)° with the imidazole and pyridine rings, respectively. Weak C-H⋯O and C-H⋯N hydrogen bonds ensure the cohesion of the crystal structure, forming a three-dimensional network.

1,3-Bis(prop-2-yn-1-yl)-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.

In the title compound, C21H12N2O3, the fused-ring system is roughly planar, the largest deviation from the mean plane being 0.084 (2) Å. The two prop-2-yn-1-yl groups are almost perpendicular to the fused ring plane, making C-C-N-C torsion angles of -103.4 (2) and -105.3 (2)°, and point in opposite directions with respect to the plane. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming a three-dimensional network.

3-Benzyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one.

The fused imidazole and pyridine rings in the title compound, C13H10BrN3O, are linked to a benzyl group. The fused ring system is essentially planar, the largest deviation from the mean plane being 0.006 (2) Å. The phenyl ring is not coplanar with the fused ring system, as indicated by the dihedral angle of 67.04 (12)°. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers.

1-Allyl-3-benzyl-1H-benzimidazol-2(3H)-one.

In the title compound, C17H16N2O, the fused benzimidazol-2(3H)-one system is essentially planar, the largest deviation from the mean plane being 0.006 (2) Šfor the carbonyl C atom. Its mean plane is almost perpendicular to the benzyl plane and to the allyl group, making dihedral angles of 80.6 (1) and 77.4 (3)°, respectively. The benzyl group and the allyl subsituent lie on opposite sides of the fused ring system. In the crystal, mol-ecules are linked by bifurcated C-H⋯O hydrogen bonds in which the carbonyl O atom acts as accepter to two aromatic C-H groups, forming a two-dimensional network parallel to (001).

6-Bromo-1,3-bis-[(1,3-dioxolan-2-yl)meth-yl]-1H-imidazo[4,5-b]pyridin-2(3H)-one.

In the title compound, C14H16BrN3O5, the N atoms adjacent to the carbonyl group in the five-membered ring are substituted by (1,3-dioxolan-2-yl)methyl groups. The fused ring system is essentially planar, with the largest deviation from the mean plane being 0.014 (2) Šfor the C atom bearing the Br atom. The first oxolane ring, attached on the side of the N atom belonging to the pyridine ring, has an envelope conformation with one of the O atoms as the flap, whereas the second oxolane ring displays a twisted boat conformation. The two oxolane rings display envelope and twisted boat conformations. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, building chains parallel to the a-axis direction.

Rapid and Efficient Access to Novel Bio-Inspired 3-Dimensional Tricyclic SpiroLactams as Privileged Structures via Meyers' Lactamization.

The concept of privileged structure has been used as a fruitful approach for the discovery of novel biologically active molecules. A privileged structure is defined as a semi-rigid scaffold able to display substituents in multiple spatial directions and capable of providing potent and selective ligands for different biological targets through the modification of those substituents. On average, these backbones tend to exhibit improved drug-like properties and therefore represent attractive starting points for hit-to-lead optimization programs. This article promotes the rapid, reliable, and efficient synthesis of novel, highly 3-dimensional, and easily functionalized bio-inspired tricyclic spirolactams, as well as an analysis of their drug-like properties.

Crystal structure, Hirshfeld surface analysis, inter-action energy and energy framework calculations, as well as density functional theory (DFT) com-putation, of methyl 2-oxo-1-(prop-2-yn-yl)-1,2-di-hydro-quinoline-4-carboxyl-ate.

In the title mol-ecule, C14H11NO3, the di-hydro-quinoline core deviates slightly from planarity, indicated by the dihedral angle of 1.07 (3)° between the two six-membered rings. In the crystal, layers of mol-ecules almost parallel to the bc plane are formed by C-H⋯O hydro-gen bonds. These are joined by π-π stacking inter-actions. A Hirshfeld surface analysis revealed that the most important contributions to the crystal packing are from H⋯H (36.0%), H⋯C/C⋯H (28.9%) and H⋯O/O⋯H (23.5%) inter-actions. The evaluation of the electrostatic, dispersion and total energy frameworks indicates that the stabilization is dominated by the dispersion energy contribution. Moreover, the mol-ecular structure optimized by density functional theory (DFT) at the B3LYP/6-311G(d,p) level is com-pared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

trans-Diaqua-bis-[2,5-bis-(pyridin-2-yl)-1,3,4-thia-diazole]cobalt(II) bis-(tetra-fluoridoborate).

The bidentate 1,3,4-thia-diazole ligand substituted by two 2-pyridyl rings (denoted L) has been found to produce the new monomeric title complex, [Co(C(12)H(8)N(4)S)(2)(H(2)O)(2)](BF(4))(2). The thia-diazole and pyridyl rings surrounding the Co atom are almost coplanar [dihedral angle = 4.35 (7)°]. The mean plane defined by these heterocyclic moieties makes a dihedral angle of 18.72 (6)° with the non-coordinated pyridyl ring. The Co(2+) cation, located at a crystallographic center of symmetry, is bonded to two ligands and two water mol-ecules in a trans configuration in an octa-hedral environment. The tetra-fluorido--borate ions can be regarded as free anions in the crystal lattice. Nevertheless, they are involved in an infinite two-dimensional network along the [010] and [101] directions of O-H⋯F hydrogen bonds.

3-Allyl-1-{[3-(4-nitro-phen-yl)-4,5-dihydro-1,3-oxazol-5-yl]meth-yl}-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.

The mol-ecular structure of the title compound, C(28)H(20)N(4)O(6), consists of three fused six-membered rings (A,B,C) and one five-membered ring (D). The latter is linked to an isoxazole ring (E) via a methyl-ene unit. A 4-nitro-phenyl substituent (F) is attached to the isoxazole. The fused five and six-membered rings (C,D) are almost coplanar with an r.m.s. deviation of 0.0345 Šand make a dihedral angle of 9.40 (8)° with ring A. The isoxazole and 4-nitro-phenyl rings (E,F) are also almost coplanar with the imidazole and the fused adjacent ring (C,D), forming a dihedral angle of 11.4 (6)°. The crystal packing displays inter-molecular C-H⋯O hydrogen bonding. An intra-molecular C-H⋯O inter-action also occurs.

trans-Diaqua-bis-[2,5-bis-(pyridin-2-yl)-1,3,4-thia-diazole]nickel(II) bis-(tetra-fluoridoborate).

The bidentate 1,3,4-thia-diazole ligand, namely, 2,5-bis-(2-pyrid-yl)-1,3,4-thia-diazole (denoted L), untested as a polydentate ligand, has been found to form the monomeric title complex, [Ni(C(12)H(8)N(4)S)(2)(H(2)O)(2)](BF(4))(2). The complex shows an octa-hedral environment of the nickel cation in which the Ni(2+) ion is located on a center of symmetry, linked to two ligands and two water molecules. In this 1:2 complex (one metal for two organic ligands) each thia-diazole ligand uses one pyridyl and one thia-diazole N atom for chelate binding. In the second pyridyl substituent, the N atom is oriented towards the same direction as the S atom of the 1,3,4-thiadiazole ring. The mean plane of the thia-diazole and pyridyl rings linked to the nickel cation forms a dihedral angle with the other pyridine ring of 18.63 (8)°. The tetra-fluorido-borate ions can be regarded as free anions in the crystal lattice. Nevertheless, they are involved in an infinite two-dimensional network parallel to ([Formula: see text]01) through O-H⋯F hydrogen bonds.

Diethyl 2,6,11-trioxo-2,3-dihydro-1H-anthra[1,2-d]imidazole-1,3-diacetate.

The title compound, C(23)H(20)N(2)O(7), consists of three fused six-membered rings (A, B and C) and one five-membered ring (D), linked to two ethyl acetate groups. The four fused rings are slightly folded around the O=C⋯C=O direction of the anthraquinone system, with a dihedral angle of 3.07 (8)° between the fused five- and six-membered rings (C and D) and the terminal ring (A). The planes through the atoms forming each acetate group are nearly perpendicular to the mean plane of the anthra[1,2-d]imidazole system, as indicated by the dihedral angles between them of 79.94 (9) and 85.90 (9)°. The crystal packing displays non-classical C-H⋯O hydrogen bonds.

1,3-Dibenzyl-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.

The mol-ecule of the title compound, C(29)H(20)N(2)O(3), contains four fused rings, three are six-membered rings and one is the five-membered imidazole ring. The fused-ring system is linked to two benzyl groups. The four fused rings are folded around the O=C⋯C=O direction of the anthraquinone, with a dihedral angle of 16.36 (8)° between the two terminal rings (A and D). The imidazole ring (D) is almost perpendicular to the two benzyl groups (E and F) with dihedral angles of 86.69 (17) and 83.15 (13)°, respectively. In the crystal, adjacent mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonding.

1,3-Bis[3-(1,3-dioxoisoindolin-2-yl)prop-yl]-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.

The title compound, C(37)H(26)N(4)O(7), is a 1H-anthra[2,1-d]imidazole-2,6,11(3H)-trione derivative having isoindolindionylpropyl substitutents attached to the imidazole N atoms. The anthraquinone fragment is buckled, the dihedral angle between the two benzene rings being 1.6 (1)°. The two isoindoline rings of the substituents of the imidazole ring are positioned on opposite sides of the five-membered ring; these are nearly mutually perpendicular [dihedral angle between isoindoline rings = 88.3 (1)°].

1,3-Bis(naphthalen-2-ylmeth-yl)-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.

The title compound, C(37)H(24)N(2)O(3), is a 1H-anthra[2,1-d]imidazole-2,6,11(3H)-trione derivative having naphthyl-methyl substitutents attached to the imidazole N atoms. The anthraquinone part of the mol-ecule is somewhat folded along the the line connecting the carbonyl bonds. The dihedral angle between the two benzene rings is 7.8 (1)°. The two naphthyl systems of the substituents of the imidazole ring are positioned on the same side of the five-membered ring; these are approximately coplanar, the dihedral angle between the napthyl systems being 4.3 (2)°.