New synthesis of diterpenoid (16<Emphasis Type="Italic">S</Emphasis>)-dihydrosteviol

A new procedure has been developed for the synthesis of diterpenoid (16S)-dihydrosteviol [(16S)-13-hydroxy-ent-kauran-19-oic acid] by acid hydrolysis (0.7% hydrochloric acid) of SWETA food sweetener and subsequent reduction of the resulting mixture of caurenoids with hydrazine hydrate over Raney nickel. The molecular geometry of (16S)-dihydrosteviol, as well as of Δ¹⁵-steviol (13-hydroxy-ent-kaur-15-en-19-oic acid), was determined for the first time by X-ray analysis.     

Synthesis of (2<Emphasis Type="Italic">S</Emphasis>,3<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-2,3-<Emphasis Type="Italic">O</Emphasis>-isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one

(2S,3S,4S)-2,3-O-Isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one was synthesized starting from D-ribose through methyl (Z)-3-(5-acetyl-2,2-acetoxyacetyl-2,2-dimethyl-1,3-dioxolan-4-yl)prop-2-enoate which was subjected to cyclization in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, followed by decarboxylation.     

<Emphasis Type="Italic">S</Emphasis>-functional derivatives of 3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-1,4-thiasilines

The first cyclic unsaturated S-functional derivatives of 4,4-diphenyl-3,4-dihydro-2H-1,4-thiasiline, S-oxide, S,S-dioxide, and S-sulfonimide, were prepared. Oxidation of the hydrolytically less stable 4,4-dimethyl-3,4-dihydro-2H-1,4-thiasiline leads to the corresponding sulfoxide and sulfone along with the ring opening products, siloxanes containing the sulfoxide or sulfonyl group.     

Features of self-organization of highly dilute solutions of (<Emphasis Type="Italic">S</Emphasis>)-, (<Emphasis Type="Italic">R</Emphasis>)-, and (<Emphasis Type="Italic">SR</Emphasis>)-methionines and related carbamides and glycolurils

Aqueous solutions of (S)-, (R)-, and (SR)-methionines (1–3); carbamide (4); (S)-, (R)-, and (SR)-N-carbamoylmethionines (5–7); glycoluril (8); and glycolurils containing (S)and (R)-methionine moieties (9 and 10) kept under natural and hypoelectromagnetic conditions were studied in comparison by a complex of physicochemical methods (dynamic and electrophoretic light scattering, conductometry, pH-metry, and dielcometry). The process of selforganization and the properties of dilute solutions (1.0?10^–15–10^–1 mol L^–1) of compounds 1–10 was shown for the first time to depend substantially on the structure of the solute and configuration of methionine (Met) enantiomers. In the series 1–3, the greatest ability to self-organization is observed for solutions of (SR)-Met in which supramolecular domains (1.0?10^–5–1.0?10^–1 mol L^–1) and nanoassociates (1.0?10^–11–1.0?10^–8 mol L^–1) are formed. The formation of nanoassociates in a concentration range of 1.0?10^–12–1.0?10^–6 mol L^–1 can be responsible for the appearance of nonmonotonic concentration dependences of the physicochemical properties of solutions of N-carbamoylmethionines 5–7, whereas the physicochemical properties are more pronounced in solution of (S)-N-carbamoylmethionine 5 than in solutions of 6 and 7. The strongest influence of the configuration of the Met enantiomer on the ability of solution to self-organization was revealed in a series of glycolurils 9, 10: solutions of 9 with the (S)-Met moiety are disperse systems in which nanoassociates are formed in a range of 1.0?10^–15–1.0?10^–5 mol L^–1, whereas in solutions of 10 with the (R)-Met fragment the ability to self-organization in the low-concentration range is absent.     

Enantioselective microbial synthesis of (<Emphasis Type="Italic">S</Emphasis>)-7,8-difluoro-3,4-dihydro-3-methyl-2<Emphasis Type="Italic">H</Emphasis>-[1,4]benzoxazine

New strains of Rhodococcus erythropolis 25 and Microbacterium paraoxydans 20-11c actinobacteria were used to obtain (S)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (99.6% ee) by enantioselective microbial hydrolysis of the corresponding racemic N-acetyl derivative.     

Synthesis of ethyl (2<Emphasis Type="Italic">E</Emphasis>,4<Emphasis Type="Italic">E</Emphasis>)- and (2<Emphasis Type="Italic">E</Emphasis>,4<Emphasis Type="Italic">Z</Emphasis>)-5-chloropenta-2,4-dienoates

An efficient synthetic approach to 2E,4E and 2E,4Z isomers of ethyl 5-chloropenta-2,4-dienoate has been developed on the basis of one-pot oxidation–olefination of readily accessible (E)- and (Z)-3-chloroprop-2-en-1-ols by the action of barium manganate and ethyl (triphenyl-λ⁵-phosphanylidene)acetate.     

Solution Thermodynamics of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis><Superscript>/</Superscript>-Ethylenebis-(salicylideneiminato)-diaquochromium(III) Chloride in Aqueous Dimethylsulphoxide

The densities, viscosities and refractive indices of N,N ^/-ethylene-bis(salicylideneiminato)-diaquochromium(III) chloride, [Cr(salen)(H₂O)₂]Cl, in aqueous dimethylsulfoxide (DMSO) with different mass fractions (w ₂ = 0.20, 0.40, 0.60, 0.80 and 1.00) of DMSO were determined at 298.15, 308.15 and 318.15 K under atmospheric pressure. From measured densities, viscosities and refractive indices the apparent molar volumes (V _φ ), standard partial molar volume (V _φ ⁰ ), the slope (S _V ^* ), standard isobaric partial molar expansibility (φ _E ⁰ ) and its temperature dependence (?φ _E ⁰ /?T) _p , the viscosity B-coefficient, its temperature dependence (?B/?T), solvation number (S _n ) and apparent molar refractivity (R _D ^φ ), etc., were calculated and discussed on the basis of ion–ion and ion–solvent interactions. These results revealed that the solutions are characterized by ion–solvent interactions rather than by ion–ion interactions and the complex behaves as a long range structure maker. Thermodynamics of viscous flow was discussed in terms of transition state theory.     

Synthesis and crystal structure of (2<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>,5<Emphasis Type="Italic">R</Emphasis>)-2-(5-bromo-2-hydroxyphenyl)-3,4-dimethyl-5-phenyl-1,3-oxazolidines

Condensation of ephedrine alkaloids with 5-bromo-2-hydroxybenzaldehyde was studied, and X-ray diffraction analysis of the synthesized (2S,4S,5R)-2-(2-hydroxy-5-bromophenyl)-3,4-dimethyl-5-phenyl-1,3-oxazolidines was performed.     

Stability of <Emphasis Type="Italic">s</Emphasis>-, <Emphasis Type="Italic">p</Emphasis>-, and <Emphasis Type="Italic">d</Emphasis>-element diphosphates in water

The mean atomic Gibbs energies of formation of (Δ _f ? _at ⁰ ) of s-, p-, and d-element diphosphates have been calculated using ion increments of the Gibbs energy (Δ _f G ⁰). The diphosphate hydrolysis kinetics is considered, and a correlation between the Δ _f ? _at ⁰ values and the hydrolysis rate constants is presented.     

Stereoselective synthesis of (<Emphasis Type="Italic">Z</Emphasis>,<Emphasis Type="Italic">E</Emphasis>)-bis(2-chloroethenyl)tellanes

A procedure for the stereoselective synthesis of dichloro[(Z)-2-chloro-2-phenylethenyl][(4E)-5- chlorooct-4-en-4-yl]-λ⁴-tellane and [(Z)-2-chloro-2-phenylethenyl][(4E)-5-chlorooct-4-en-4-yl]tellane has been developed on the basis of anti-addition of tellurium tetrachloride–phenylacetylene monoadduct to oct-4-yne.     

Sensitive RP-HPLC Enantioseparation of (<Emphasis Type="Italic">RS</Emphasis>)-Ketamine via Chiral Derivatization Based on (<Emphasis Type="Italic">S</Emphasis>)-Levofloxacin

Enantioseparation of (RS)-ketamine has been achieved in the form of its diastereomeric hydrazones. A new chiral reagent was synthesized from enantiomerically pure (S)-levofloxacin by converting its carboxyl group into a hydrazide derivative: the reagent provided a reaction site for the ketonic group present in (RS)-ketamine. Because of the structural feature of the chiral reagent formation of diastereomeric hydrazones of (RS)-ketamine was successful without protection of its amino group. The diastereomeric hydrazones were separated on a reversed-phase C₁₈ column with a mobile phase consisting of MeCN and 0.1% TFA under gradient elution from 35 to 65% of MeCN. The limit of detection was found to be 3.2 and 3.4 nmol for first and second eluting diastereomeric hydrazones, respectively. The separation mechanism and elution order of the diastereomeric hydrazones were proposed and supported by developing the geometry optimized ‘lowest energy’ structures of the two diastereomeric hydrazones using DFT-based Gaussian software.     

Nitrosative Stress Response in <Emphasis Type="Italic">Vibrio cholerae</Emphasis>: Role of <Emphasis Type="Italic">S</Emphasis>-Nitrosoglutathione Reductase

Vibrio cholerae, the causative agent of cholera, poses serious threats to humans worldwide. V. cholerae faces host inflammatory response and encounters nitrosative stress before establishing successful colonization. It is not clear how V. cholerae combats nitric oxide and reactive nitrogen species. In the present study, we used three clinical strains of V. cholerae and tested their nitrosative stress response pattern towards sodium nitroprusside (SNP) and S-Nitrosoglutathione (GSNO). Among them, V. cholerae, belonging to both O1 and O139 serotypes, showed moderate resistance to SNP and GSNO. However, a V. cholerae strain belonging to non O1 and non O139 showed sensitivity to SNP but resistance towards GSNO. Reduced glutathione and glutathione reductase play a significant role to combat nitrosative stress in V. cholerae. This is the first report where we show the presence of GSNO reductase activity in V. cholerae and that it plays an important role to detoxify S-Nitrosoglutathione. GSNO reductase activity of V. cholerae was regulated by posttranslational modification through S-nitrosylation under in vitro conditions which could be reversed by dithiothreitol (DTT). In addition, we show that biofilm formation remained unaffected under nitrosative stress in V. cholerae.     

Gas-chromatographic determination of trace <Emphasis Type="Italic">S</Emphasis>-[2-(<Emphasis Type="Italic">N,N</Emphasis>)-diethylamino)ethyl]methylphosphonothioic acid in water

A procedure is proposed for the gas-chromatographic determination of S-[2-(N,N)-diethylamino) ethyl]methylphosphonothioic acid (monothiol) in water at a level of 5 × 10^?5%. The procedure is based on the extraction of monothiol from water by liquid-liquid extraction, treatment of the extract with isopropanol in the presence of AgNO₃ and with diazomethane to obtain O-isopropyl-O-methyl methylphosphonate, and the chromatographic detection of the derivative obtained with a flame-photometric detector. The relative error of determining monothiol in water does not exceed 35%; the time of analysis is 60 min.     

Synthesis and piezoelectric properties of <Emphasis Type="Italic">N</Emphasis>-phthaloylglutamic acid derivatives

The (S,S)- and (R,R)-enantiomers of dimethyl 2,4-diphthalimidoglutarate were synthesized by nucleophilic substitution of bromine in dimethyl (2S,4RS)-4-bromo-N-phthaloyl-glutamate upon treatment with potassium phthalimide, followed by separation. The crystal structure of the obtained compounds was studied by X-ray diffraction. Crystals of enantiomerically pure dimethyl 4-hydroxy- and 4-phthalimido-N-phthaloylglutamates were found to possess a noticeable piezoelectric activity.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>,<Emphasis Type="Italic">O</Emphasis>-Dialkyl <Emphasis Type="Italic">S</Emphasis>-(1,1-dimethyl-2-oxoethyl) dithiophosphates and their reactions with N-nucleophiles

O,O-Dialkyl S-(1,1-dimethyl-2-oxoethyl) dithiophosphates, 2-(dialkoxythiophosphorylthio)-substituted aldehydes with branched carbon groups, were obtained by hydrolysis of phosphoryl-containing iminium salts. The reaction with primary amines results in imines containing acetal group in different positions. Tri- and tetra-substituted perhydro-1,3-diazoles and oxazoles containing a phosphorus atom in the side chain were prepared by reacting the aldehydes with O,Nand N,N-dinucleophiles.     

<Emphasis Type="Italic">S</Emphasis>- to <Emphasis Type="Italic">N</Emphasis>-Palmitoyl Transfer During Proteomic Sample Preparation

N-palmitoylation has been reported in a number of proteins and suggested to play an important role in protein localization and functions. However, it remains unclear whether N-palmitoylation is a direct enzyme-catalyzed process, or results from intramolecular S- to N-palmitoyl transfer. Here, using the S-palmitoyl peptide standard, GC_palmLGNAK, as the model system, we observed palmitoyl migration from the cysteine residue to either the peptide N-terminus or the lysine side chain during incubation in both neutral and slightly basic buffers commonly used in proteomic sample preparation. Palmitoyl transfer can take place either intra- or inter-molecularly, with the peptide N-terminus being the preferred migration site, presumably because of its lower basicity. The extent of intramolecular palmitoyl migration was low in the system studied, as it required the formation of an entropically unfavored macrocycle intermediate. Intermolecular palmitoyl transfer, however, remained a tangible problem, and may lead to erroneous reporting of in vivo N-palmitoylation. It was found that addition of the MS-compatible detergent RapiGest could significantly inhibit intermolecular palmitoyl transfer, as well as thioester hydrolysis and DTT-induced thioester cleavage. Finally, palmitoyl transfer from the cysteine residue to the peptide N-terminus can also occur in the gas phase, during collision-induced dissociation, and result in false identification of N-palmitoylation. Therefore, one must be careful with both sample preparation and interpretation of tandem mass spectra in the study of N-palmitoylation.

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Graphical Abstract ?

     

Synthesis and structure of bis(1,2-diaminoethane) copper(II) bis(<Emphasis Type="Italic">o</Emphasis>-hydroxybenzoate) monohydrate and <Emphasis Type="Italic">trans</Emphasis>-diaquabis(1,2-diaminoethane)copper(II) bis(<Emphasis Type="Italic">o</Emphasis>-aminobenzoate)

X-ray structural analysis has been performed for two complex compounds: Cu(en)₂(o-HB)₂H₂O (I) (a = 16.873(4) Å, b = 8.713(2) Å, c = 14.803(3) Å, β = 91.15(2)°, V = 2175.8(8) ų, C2/c, Z = 4, R(F) = 0.0263, 1516 reflections with I > 3σ (I)) and [Cu(en)₂(OH₂)₂]²⁺(o-AB^?)₂ (II) (a = 7.488(5) Å, b = 22.122(8) Å, c = 7.856(5) Å, β = 118.77(2)°, V = 1140.7(11) ų, P2₁/n, Z = 2, R(F) = 0.0432, 1684 reflections with I > 3σ(I)) synthesized under identical conditions (en is ethylenediamine, o-HB is o-hydroxybenzoate, and o-AB is o-aminobenzoate). Although the compounds were assumed to have similar structures and the Cu-Lig bond lengths and the cis and trans angles are acceptable for an octahedral structure, the geometric parameters of o-HB suggest that the copper atom has a plane square environment.     

<Emphasis Type="Italic">N</Emphasis>-allyl and <Emphasis Type="Italic">N</Emphasis>-propargyl trifluoromethanesulfonimides. Theoretical analysis

Tautomers of N-allyl- and N-propargyl-substituted trifluoromethanesulfonimides (CF₃SO₂)₂NR (R = CH₂CH=CH₂, Z/E-CH=CHMe, CH₂C≡CH, CH=CH=CH₂, C≡CCH₂) were calculated by the DFT (B3LYP, wB97XD, PBE1PBE), MP2, and CBS-QB3 methods. The results were compared with the theoretical data for the corresponding amines and amides NHRR¹ (R¹ = H, CF₃SO₂). It was shown that there is no conjugation between the nitrogen atom and C=C bond and that conjugation exists with the C≡C bond with electron density displacement toward the nitrogen atom. The calculations of anions derived from N-allyl- and N-propargyl-trifluoromethanesulfonimides revealed the possibility of their rearrangement with elimination of trifluoromethanesulfinate anion and formation of its H-complex with N-(prop-2-en-1-ylidene)trifluoromethanesulfonamide or N-(prop-2-yn-1-ylidene)trifluoromethanesulfonamide.     

Regioselectivity in the reactions of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)-sulfonamides with 1<Emphasis Type="Italic">H</Emphasis>-pyrrole and 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrole

N-(2,2,2-Trichloroethylidene)arenesulfonamides react with 1H-pyrrole and 1-methyl-1H-pyrrole to give the corresponding N-[2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethyl]arenesulfonamides. The reaction of N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide with pyrrole leads to a mixture of 2-mono-and 2,5-disubstituted pyrroles, whereas in the reaction with 1-methyl-1H-pyrrole only the 2-substituted compound is formed. N-(2,2-Dichloro-2-phenylethylidene)-4-methylbenzenesulfonamide reacts with 1H-pyrrole to form N-[2,2-dichloro-2-phenyl-1-(1H-pyrrol-2-yl)ethyl]-4-methylbenzenesulfonamide, and its reaction with 1-methyl-1H-pyrrole gives a mixture of 2-and 3-monosubstituted derivatives. The results of quantum-chemical calculations of the initial reactants and products indicate that the process is orbital-controlled. A good agreement is observed between the experimental data and theoretical conclusions concerning the dependence of the reaction regioselectivity on the nature of substituents in the electrophile molecule.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.