Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization

A novel approach for synthesizing the key dolutegravir intermediate is described via MgBr2-promoted intramolecular cyclization. Condensation of commercially available methyl oxalyl chloride and ethyl 3-(N,N-dimethylamino)acrylate afforded the vinylogous amide in an excellent yield. Subsequent substitution by aminoacetaldehyde dimethyl acetal and methyl bromoacetate gave rise to the expected precursor for cyclization, which was promoted by MgBr2 to highly selectively convert into pyridinone diester. The key dolutegravir intermediate was finally prepared by the selective hydrolysis of the corresponding diester via LiOH.

ON ONE APPROACH TO DETERMINING THE VORTEX SOUND SOURCE

The work consists of five sections and a bibliographic list. The first section provides answers to questions about the relevance, the applied value of the study, as well as the need to develop new approaches that allow modeling vortex structures in engineering practice. In the second section, some mathematical models and approaches used to solve problems of vortex dynamics are considered. The third section is devoted to solving the problem of determining the main parameters of the flow in the core of a vortex ring for given geometric dimensions. It is shown that a turbulent vortex ring is obtained as a result of the interaction of two vortex columns. The fourth section is devoted to methods for characterizing a concentrated vortex as a source of acoustic vibrations. As an object of research, the flow in the core of a turbulent vortex ring is considered. It is assumed that the core of the vortex ring has the shape of a torus. An approach is proposed that makes it possible to establish a strict link between the main flow parameters and the shape of the vortex ring. The aim of this work is to obtain the flow parameters in the core of a vortex ring with their subsequent substitution into the acoustic-vortex equation to analyze the source of acoustic oscillations. It is also necessary to show the presence of a structure in the vortex ring corresponding to some point symmetry and, thus, to abandon the concept of the circular symmetry of the core of the vortex ring. The proposed approach is based on the assertion that a vortex ring can be represented as a set formed according to a “rule” that determines a spatial geometric shape. As a result, an approach was proposed for analyzing the vortex ring as a source of acoustic oscillations, and it was also formulated and theoretically substantiated that the core of a turbulent vortex ring having the shape of a torus can be considered as a result of the interaction of two vortex columns.

The Synthesis of α-Aminophosphonates via Enantioselective Organocatalytic Reaction of 1-(N-Acylamino)alkylphosphonium Salts with Dimethyl Phosphite

α-Aminophosphonic acids are phosphorus analogues of α-amino acids. Compounds of this type find numerous applications in medicine and crop protection due to their unique biological activities. A crucial factor in these activities is the configuration of the stereoisomers. Only a few methods of stereoselective transformation of α-amino acids into their phosphorus analogues are known so far and all of them are based on asymmetric induction, thus involving the use of a chiral substrate. In contrast, we have focused our efforts on the development of an effective method for this type of transformation using a racemic mixture of starting N-protected α-amino acids and a chiral catalyst. Herein, a simple and efficient stereoselective organocatalytic α-amidoalkylation of dimethyl phosphite by 1-(N-acylamino)alkyltriphenylphosphonium salts to enantiomerically enriched α-aminophosphonates is reported. Using 5 mol% of chiral quinine- or hydroquinine-derived quaternary ammonium salts provides final products in very good yields up to 98% and with up to 92% ee. The starting phosphonium salts were easily obtained from α-amino acid derivatives by decarboxylative methoxylation and subsequent substitution with triphenylphosphonium tetrafluoroborate. The appropriate self-disproportionation of enantiomers (SDE) test for selected α-aminophosphonate derivatives via achiral flash chromatography was performed to confirm the reliability of the enantioselectivity results that were obtained.

Die (1-Cyclohepta-2,4,6-trienyl)thiolato-verbrüuckten Zweikernkomplexe – Mn2(CO)8(μ2-SC7H7)2 und Mn2(CO)6(C≡NtBu)2(μ2-SC7H7)2 / The (1-Cyclohepta-2,4,6-trienyl)thiolato-Bridged Dinuclear Complexes Mn2(CO)8(μ2-SC7H7)2 and Mn2(CO)6(C≡NtBu)2(μ2-SC7H7)2

The reactions of either Mn2(CO)10 (under irradiation) or Mn(CO)5X (X = Cl, Br) with di(1-cyclohepta-2,4,6-trienyl) sulfide, S(C7H7)2 (1), led to the organothiolato-bridged dimer [Mn(CO)4(μ2-SC7H7)]2 (2) in addition to ditropyl, (C7H7)2. Subsequent substitution of two carbonyl ligands in 2 for tert-butyl isocyanide gave [Mn(CO)3(C≡NtBu)(μ2-SC7H7)]2 (3). The molecular structures of the centrosymmetric dimers 2 and 3 have been determined by X-Ray crystallography. Both 2 and 3 contain a planar Mn2S2 core with the 1-cyclohepta-2,4,6-trienyl substituents in anti-position. The structural parameters of dinuclear carbonylmanganese complexes containing organothiolato or thioether bridges are discussed.

Formation of organosilicon compounds 117:1 C-brominated 1,3,5-trisilacyclohexanes and their reactions with BuLi

The photobromination of 1,1,3,3,5,5-hexamethyl-1,3,5-trisilacyclohexane (1) almost exclusively attacks CH2 groups and results in 2,2-dibromo-trisilacyclohexane (2) as well as 2,2,4,4-tetrabromo-trisilacyclohexane (3) in high yields. Starting from a mixture of C-brominated trisilacyclohexanes the isomeric 2,2,9-tribromo-1,3,3,5,5,8,8,10,10,13,13-undecamethyl-1,3,5,8,10,13-hexasilabicyclo[7.2.2]tridec-6-yne (6) had been obtained in very low yield in an attempt to establish a preparative route to adamantanes with a C4Si6 skeleton, i.e., with C bridgeheads and SiR2 bridges. By ICl-cleavage of a Si—methyl bond in 2 and subsequent substitution with Br3CLi, the trisilacyclohexane 4 with functional groups in opposite positions of the ring can be obtained. Linking the step-by-step synthesized Cl-Me2Si-C=C-SiMe2-CH2-SiMe2-Ph to the CBr3 group of 4 results after HBr-cleavage of the Si—Ph bond in (ω-bromo-octynyl)-trisilacyclohexane (12). A ring closure of 12 would result in an isomeric hexasila bicyclo[7.2.2]tridec-6-yne. The compounds were characterized by 1H, 13C, and 29Si NMR spectra. Additionally, the molecular structures of 4 and 6 were confirmed by X-ray single crystal investigations.Key words: 1,1,3,3,5,5-hexamethyl-1,3,5-trisilacyclohexane, bromination, 2,2,9-tribromo-1,3,3,5,5,8,8,10,10,13,13-undecamethyl-1,3,5,8,10,13-hexasilabicyclo[7.2.2]tridec-6-yne, carbosilane synthesis, NMR data, crystal structure investigation.

Analysis of upstream activation of thevnfHpromoter ofAzotobacter vinelandii

BAL-31 deletion products of the DNA fragment containing the vnfH promoter and upstream region, when cloned in a transcriptional fusion vector and analyzed for vnfH expression in Azotobacter vinelandii, revealed that the upstream activator sequence of the vnfH promoter lies about 140 nucleotides upstream of the promoter. Subsequent substitution and deletion analysis by oligonucleotide-directed mutagenesis in the upstream region of the vnfH promoter showed that sequences 5'-GTACCATGCGGAAC-3' and 5'-GTACCTGCGGGTAC-3', located 170 and 140 nucleotides upstream of the vnfH promoter, respectively, are both required for vnfH expression. Addition of four nucleotides in the intervening sequence between the vnfH promoter and the putative VnfA (analog of NifA of the conventional molybdenum-dependent nitrogen-fixation pathway) binding site resulted in a drastic reduction of expression from the vnfH promoter in Azotobacter vinelandii, where as addition of 10 nucleotides in the intervening sequence did not affect the expression. Therefore, the face of the helix-dependent contact appeared to be important. DNA bending seemed to play a crucial role in expression from vnfH promoter. The intervening sequence exhibited characteristics of sequence-dependent intrinsically curved DNA, as shown by anomalous low gel mobility with polyacrylamide gel electrophoresis, electron microscopy, and computer simulated curvature analysis. Distamycin at very low concentrations significantly reduced the anomaly in electrophoretic mobility of the intervening DNA sequence.Key words: Azotobacter vinelandii, vnfA, vnfH, promoter-lacZ fusion, DNA bending.