MbnC is not required for the formation of the N-terminal oxazolone in the methanobactin from Methylosinus trichosporium OB3b.

Methanobactins (MBs) are ribosomally synthesized and post-translationally modified peptides (RiPPs) produced by methanotrophs for copper uptake. The post-translational modification that define MBs is the formation of two heterocyclic groups with associated thioamines from X-Cys dipeptide sequences. Both heterocyclic groups in the MB from Methylosinus trichosporium OB3b (MB-OB3b) are oxazolone groups. The precursor gene for MB-OB3b, mbnA , which is part of a gene cluster that contains both annotated and unannotated genes. One of those unannotated genes, mbnC , is found in all MB operons, and in conjunction with mbnB , is reported to be involved in the formation of both heterocyclic groups in all MBs. To determine the function of mbnC , a deletion mutation was constructed in M. trichosporium OB3b, and the MB produced from the Δ mbn C mutant was purified and structurally characterized by UV-visible absorption spectroscopy, mass spectrometry and solution NMR spectroscopy. MB-OB3b from Δ mbn C was missing the C-terminal Met and also found to contain a Pro and a Cys in place of the pyrrolidiny-oxazolone-thioamide group. These results demonstrate MbnC is required for the formation of the C-terminal pyrrolidinyl-oxazolone-thioamide group from the Pro-Cys dipeptide, but not for the formation of the N-terminal 3-methylbutanol-oxazolone-thioamide group from the N-terminal dipeptide Leu-Cys. IMPORTANCE A number of environmental and medical applications have been proposed for MBs, including bioremediation of toxic metals, nanoparticle formation, as well as for the treatment of copper- and iron-related diseases. However, before MBs can be modified and optimized for any specific application, the biosynthetic pathway for MB production must be defined. The discovery that mbnC is involved in the formation of the C-terminal oxazolone group with associated thioamide but not for the formation of the N-terminal oxazolone group with associated thioamide in M. trichosporium OB3b suggests the enzymes responsible for post-translational modification(s) of the two oxazolone groups are not identical.

Catalytic Asymmetric Synthesis of syn Aldols with Methyl Ketone Functionality and anti Aldols with a Thioamide Group

Catalytic asymmetric syntheses of syn aldols with a methyl ketone functionality were studied to confirm the generality of the methodology. In addition, catalytic asymmetric synthesis of anti aldols with a thioamide group was carefully examined, giving the desired products, albeit with moderate diastereoselectivity.

The crystal structure of 1-(2-hydroxy-5-methoxyphenyl)ethanone 4,4-dimethylthiosemicarbazone

The asymmetric unit of the title compound, C12H17N3O2S, contains two independent molecules,AandB. Both molecules are nearly planar with the dihedral angle between the mean planes of the thioamide group and benzene ring being 7.5 (1)° inAand 4.3 (2)° inB. In each molecule, the hydroxy group participates in intramolecular O—H...N hydrogen bonding, while the amino H atom is not involved in hydrogen bonding because of the steric hinderence caused by two neighboring methyl groups. In the crystal, the individual molecules are linked by weak C—H...O hydrogen bonds, formingA–AandB–Binversion dimers. The dimers are linkedviaC—H...π interactions which help stabilize the packing.

Crystal structure of (2Z)-2-{(5Z)-5-[3-fluoro-2-(4-phenylpiperidin-1-yl)benzylidene]-4-oxo-3-(p-tolyl)-1,3-thiazolidin-2-ylidene}-N-(p-tolyl)ethanethioamide dimethyl sulfoxide monosolvate

The title compound, C37H34FN3OS2·C2H6OS, was obtained by the Knoevenagel condensation. The thiazolidine ring is essentially planar (r.m.s. deviation = 0.025 Å) and forms dihedral angles of 4.2 (3), 68.60 (14) and 39.57 (15)° with the attached thioamide group,p-tolyl group benzene ring and fluoro-substituted benzene ring, respectively. The exocyclic double bonds are in aZconfiguration. In the crystal, the dimethyl sulfoxide solvent molecule is connected to the main moleculeviaan N—H...O hydrogen bond. Weak C—H...O hydrogen bonds link the components of the structure into a two-dimensional network parallel to (10-1). Weak intramolecular C—H...S hydrogen bonds are also observed. The crystal is an inversion twin with a ratio of twin components 0.78 (2):0.22 (6).

Partial conversion of thioamide into nitrile in a copper(II) complex of 2,6-diacetylpyridine bis(thiosemicarbazone), a drug prototype for Alzheimer's disease

This work reports the crystal structure of [(Z)-2-((E)-1-{6-[1-({[amino(sulfanidyl-κS)methylidene]amino}imino-κN)ethyl]pyridin-2-yl-κN}ethylidene)-1-cyanohydrazinido-κN1]copper(II), [Cu(C11H11N7S)], the first description of a copper(II) complex of 2,6-diacetylpyridine bis(thiosemicarbazone) showing partial conversion of a thioamide group to a nitrile group. The asymmetric ligand coordinates to the metal centre in anN,N′,N′′,S-tetradentate mannerviathe pyridine N atom, an imine N atom, the hydrazinide N atom and the sulfanidyl S atom, displaying a square-planar geometry. Ligand coordination results in two five-membered chelate rings and one six-membered chelate ring, and in crystal packing based on N—H...N hydrogen bonds of the cyanohydrazinide and hydrazinecarbothioamidate arms of the ligand. The correlation between the partial conversion upon metal complexation, H2S release and possible effects on the activity of bis(thiosemicarbazone)s as drug prototypes for Alzheimer's disease is also discussed.

Synthesis of New Imidazolidine and Tetrahydropyrimidine Derivatives

Synthesis of new imidazolidine and tetrahydropyrimidine derivatives 3a, b and 4a–c as cyclic 1,3-diamines under two reaction conditions (A and B) is described. Under reaction conditions-A, a suspension of (E)-2-cyano-2-(oxazolidin-2-ylidene)ethanethioamide 1 (1 eq.) and diaminoalkanes 2a–e (2 eq.) in absolute ethanol is heated under reflux for 16–22 h to afford 3a, b and 4a–c. Alternatively, under reaction conditions-B, a solution of thioamide 1 (1 eq.) in diaminoalkanes 2a–e (3 eq.) is stirred under solvent-free conditions at room temperature for 3 days to give desired products. Reaction conditions-A for having higher yields, shorter reaction times, and required less diamines is more effective than reaction conditions-B. Oxazolidine ring opening is observed by reacting compound 1 with all of the diamines 2a–e, but the thioamide group only reacts with nonbulky diamines 2a, b. The chemical structures of novel compounds were confirmed by 1H NMR, 13C NMR, elemental analysis, and FT-IR spectrometry.

4-Thiocarbamoylpyridin-1-ium iodide

The title salt, C6H7N2S+·I−, crystallizes with two independent cations and two anions in the asymmetric unit. In one of the cations, the dihedral angle between the pyridinium ring and the thioamide group is 28.9 (2)°; in the other it is 33.5 (2)°. In the crystal, N—H...S and C—H...S hydrogen bonds link the independent cations into pairs. These pairs form a three-dimensional network through additional N—H...I and C—H...I hydrogen bonds to the anions.