Reaction of β‐cyano esters with hydrazine hydrate. Unexpected formation of dipyrrolo[1,2‐b:1′,2′‐e][1,2,4,5]tetrazine,a novel ring system

Some intermediates and by‐products of the title reaction, known to yield 6‐hydrazinopyridazine‐3‐one derivatives, were isolated or detected when the amount of hydrazine hydrate used to react with two model β‐cyano esters was reduced to less than two equivalents. N'‐(1‐amino‐4‐hydrazino‐4‐oxo‐2‐phenylbutyli‐dene)‐4‐hydrazino‐4‐oxo‐2‐phenylbutanehydrazonamide and 3,3,8,8‐tetramethyl‐2,3,7,8‐tetrahydro‐1H,6H‐dipyrrolo[1,2‐b:1′,2′‐e][1,2,4,5]tetrazine‐1,6‐dione were isolated as the terminal products of side‐reactions; they were unreactive to hydrazine. The latter compound is a derivative of a novel ring system. Mechanism of the reaction was proposed.     

Mass spectrometric investigation of gallium and zirconium complexes with octaethylporphyrin and tetraphenylporphyrin

Gallium and zirconium octaethylporphyrin (OEP) and tetraphenylporphyrin (TPP) were examined by electrospray ionization (ESI) mass spectrometry. All systems were prepared in dichloromethane with addition of a stabilizing lipophilic anionic agent, sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB). In the solutions examined both monomeric and dimeric metalloporphyrins were observed. In the gallium-OEP mass spectrum the ion registered at m/z 601 was attributed to monomeric [Ga(OEP)](+) and that at m/z 1219 to the dimeric form, [[Ga(OEP)](2)OH](+). Peaks appearing in the ESI mass spectra of zirconium systems were substantially less intense, probably owing to the relatively low stability of complexes of this metal caused by its different geometry preferences. The most abundant monomeric zirconium-OEP complexes were [[Zr(OEP)OH]](+) (m/z 639) and [Zr(OEP)Cl](+) (m/z 657), and dimeric [[Zr(OEP)OH](2)](2+) (m/z 639). Analogous species were observed in the Zr(TPP) system: monomeric [[Zr(OEP)OH]](+) (m/z 719) and [Zr(TPP)Cl](+) (m/z 737) and dimeric [[Zr(TPP)OH](2)](2+) (m/z 719). In both cases series of other dimers, e.g. [[Zr(OEP)](2)O(2)H](+) (m/z 1277), [[Zr(OEP)OH](2)Cl](+) (m/z 1313), [Zr(TPP)(2)O(2)H](+), (m/z 1437), [[Zr(TPP)OH](2)OH](+) (m/z 1455) and [[Zr(TPP)OH](2)Cl](+) (m/z 1473), appeared. The results obtained confirmed the hypothesis concerning the formation of dimeric metalloporphyrins in solutions containing stabilizing lipophilic anions. It also allowed us to explain the super-Nernstian slopes of the calibration curves towards primary anions of ion-selective electrodes with membranes containing the examined metalloporphyrins.     

Reaction of 5,5-diphenyl-2-thiohydantoin with ethyl chloroacetate: Synthesis and crystal and molecular structure of 2,3,5,6-tetrahydroimidazo-[2,1-b]-thiazol-3,6-dione

The crystal and molecular structure of the title compound, obtained as a result of intramolecular cyclization of 5,5-diphenyl-2-carboxymethylmercaptohydantoin, has been determined from X-ray diffractometer data. The finalR was 0.049 for 1869 reflections. The conformation of the molecule was found to approximate to the conformations of other similar compounds, but owing to the presence of a C=O group in the thiazol ring, important differences in conjugated bonds system were observed.     

The Smearing Out of the Thermal Initial Conditions Created in a Planck Era

In this paper the quantum heat transport in a Planck gas in the presence of the potential (other than the thermal one) is investigated. The new quantum heat transport equation which generalizes our potential-free QHT is developed. The thermal wave solution of QHT for a Planck gas is obtained and a condition for distortionless propagation of thermal wave is formulated. It is argued that the initial conditions of the Beginning (i.e., at t=0) are smeared in the time scale of the Planck time.     

Chiral Non-racemic Bis(vicinal 1,2-Diamines): 4,5-Diamino-N-(3,4-diaminobutyl)pentanamide Tetrahydrochloride, N,N′-Bis[3,4-bis (t-butoxycarbonylamino)butyl]urea and N,N′Bis

The reaction of (R) or (S)-N⁴,N⁵-bis(t-butoxycarbonyl)-4,5-diaminopentanoic acid (6) with (R) or (S)-N³,N⁴-bis(t-butoxycarbonyl)-3,4-diaminobutylisocyanate (8) catalyzed by 4-dimethylamino pyridine (DMAP), leads to the synthesis of (R,R), (S,S), (R,S) and (S,R) isomeric amides (11 a — d) The addition of adipic acid monomethyl ester to (R) or (S) isocyanate, followed by saponification, acidification and subsequent reaction with the second molecule of (R) or (S) isocyanate allows isolation of the (R,R), (S.S) and the meso isomers of N,N′-bis[3,4-bis(t-butoxycarbonylamino) butyl]hexanediamide (17) Removal of protecting groups with HCl/EtOH affords chiral non-racemic molecules having two free vicinal diamine units.     

The reactions of ureas with glyoxylic acid and methyl glyoxylate

The reactions of urea, methylurea and dimethylureas with glyoxylic acid and its methyl ester to give α-substituted hydantoic acid derivatives (4, 5, 6, 7) and substituted allantoic acid derivatives (8) is discussed. The cyclization of the hydantoates and allantoates to 5-substituted hydantoins (11, 12) is also described.     

Applications and Restrictions of Integrated Genomic and Metabolomic Screening: An Accelerator for Drug Discovery from Actinomycetes?

Since the golden age of antibiotics in the 1950s and 1960s actinomycetes have been the most prolific source for bioactive natural products. However, the number of discoveries of new bioactive compounds decreases since decades. New procedures (e.g., activating strategies or innovative fermentation techniques) were developed to enhance the productivity of actinomycetes. Nevertheless, compound identification remains challenging among others due to high rediscovery rates. Rapid and cheap genome sequencing as well as the advent of bioinformatical analysis tools for biosynthetic gene cluster identification in combination with mass spectrometry-based molecular networking facilitated the tedious process of dereplication. In recent years several studies have been dedicated to accessing the biosynthetic potential of Actinomyces species, especially streptomycetes, by using integrated genomic and metabolomic screening in order to boost the discovery rate of new antibiotics. This review aims to present the various possible applications of this approach as well as the newly discovered molecules, covering studies between 2014 and 2021. Finally, the effectiveness of this approach with regard to find new bioactive agents from actinomycetes will be evaluated.