Regioselective and Stereoselective Synthesis of the 3-Aryl-4- phosphoryl-1, 2, 4-triazoline-5-ones

Regioselective cyclization of 1-acylthiosemicarbazides has been shown to be an excellent method for the synthesis of triazoles, thiadiazoles and oxadiazoles, with a variety of potential biological activities1-6 and utilities as pharmacological properties7…     

Exploring the effectiveness of the TSR-based protein 3-D structural comparison method for protein clustering,and structural motif identification and discovery of protein kinases,hydrolases, and SARS-CoV-2’s protein via the application of amino acid grouping

Development of protein 3-D structural comparison methods is essential for understanding protein functions. Some amino acids share structural similarities while others vary considerably. These structures determine the chemical and physical properties of amino acids. Grouping amino acids with similar structures potentially improves the ability to identify structurally conserved regions and increases the global structural similarity between proteins. We systematically studied the effects of amino acid grouping on the numbers of Specific/specific, Common/common, and statistically different keys to achieve a better understanding of protein structure relations. Common keys represent substructures found in all types of proteins and Specific keys represent substructures exclusively belonging to a certain type of proteins in a data set. Our results show that applying amino acid grouping to the Triangular Spatial Relationship (TSR)-based method, while computing structural similarity among proteins, improves the accuracy of protein clustering in certain cases. In addition, applying amino acid grouping facilitates the process of identification or discovery of conserved structural motifs. The results from the principal component analysis (PCA) demonstrate that applying amino acid grouping captures slightly more structural variation than when amino acid grouping is not used, indicating that amino acid grouping reduces structure diversity as predicted. The TSR-based method uniquely identifies and discovers binding sites for drugs or interacting proteins. The binding sites of nsp16 of SARS-CoV-2, SARS-CoV and MERS-CoV that we have defined will aid future antiviral drug design for improving therapeutic outcome. This approach for incorporating the amino acid grouping feature into our structural comparison method is promising and provides a deeper insight into understanding of structural relations of proteins.     

Synthesis and structure–activity relationship study of cytotoxic lupane-type 3β-O-monodesmosidic saponins with an extended C-28 side chain

A concise synthesis of lupane triterpenes with an elongated carbon chain at the C-28 position, as well as saponins containing d-mannose, l-arabinose, and l-rhamnose moieties at the C-3 position is described. The overall synthesis of the new triterpenes involved seven linear steps starting from natural betulin: selective protection of a hydroxyl group, oxidation, elongation of the carbon chain by Grignard reaction, and deoxygenation. O-Glycosides were obtained by glycosylation of triterpenes with classical Schmidt's donors. Additionally, all new compounds were evaluated in vitro for their cytotoxic activities. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. The therapeutical index of active triterpenes is very high, since almost none of them were cytotoxic for normal BJ fibroblasts. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.     

Studies of 2-Substituted 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-ones as Precursors for the Synthesis of N-Alkyl-β-Amino Acids

1,3-Oxazolidin-5-ones and 1,3-oxazinan-6-ones have been shown to be useful precursors for the synthesis of N-methyl α- and β-amino acids, respectively. The methodology has now been expanded to allow for the synthesis of N-alkyl-β-amino acids.     

Manganese Triacetate Oxidation of 3β, 3aβ, 6-Trimethyl-3a, 7aβ-dihydro-2(3H), 5(4H)-benzofurandione

The manganese triacetate oxidation of hindered α¹-positions in a model enone, 3β, 3aβ, 6-trimethyl-3a, 7aβ-dihydro-2(3H), 5(4H)-benzofurandione, provided a procedure for the introduction of the α′-hydroxyenone functionality characteristic of the A ring of certain quassinoids.     

X-ray Structure of 1- (3' -Phenyl-4' -morpholinyl-2' 5' - dithiole-1' - ylidene)-3, 4-biscarboethoxy-2-thionaphthalene

1INTR0DUCTIONa-Thiocarbonylthioformamideshavebeensynthesizedsince1980[l-23,however,thereisn0reP0rtofthesecomP0undsrelatedtheirpropertiesandreactivities(3).Ac-cordingtothepublishedpapers('-",adithioketone,adithioesterandadithioth-ioesteraresnitablefort4 2JcycloadditionwithalkenicandacetylenicdienophileS.Wewanttoknowwhethera-thiocarbonylthioformamideshavethesamecharacters,thereforethereactionofathiobenzoylthioformmorpholine(1)withdiethylacetylenedicarboxylate(2)wasexplored.Theredultsshowth…     

Synthesis and Molecular Structure of 5, 5-Dimethyl-2- (4' -methoxy)phenyl-1, 3, 2- thiazaphospholidine-4-thione 2-sulfide

1 INTRODUCTION In our previous study [1], we found that 1, 3, 2-thiazaphospholidine-4-thione 2-sulfide deriva- tives possessed various bioactivities such as herbicidal, antiviral, fungicidal activity, Which the is strongly held our interest to exploit new method for the synthesis of such phosphorohe- terocycles and investigate their biological activities. Different method for the preparation of 1, 3, 2-thiazaphospholidine-4-thione (one) 2-sulfides have been reported [2~4]. According to …     

Highly diastereoselective and enantioselective Michael addition of 5H-oxazol-4-ones to α,β-unsaturated ketones catalyzed by a new bifunctional organocatalyst with broad substrate scope and applicability

A new thiourea-tertiary amine bifunctional catalyst derived from L-tert-leucine was developed and provides excellent stereocontrol in a novel and direct Michael addition of 5H-oxazol-4-ones to α,β-unsaturated ketones with much broad substrate scope. The conjugate addition products with chiral vicinal quaternary and tertiary stereocenters can be easily transformed to structurally interesting compounds or building blocks.     

Heats of reaction of HMo(CO)3C5H5 with CCl4 and CBr4 and of NaMo(CO)3C5H5 with I2 and CH3. Solution thermochemical study of the MoX bond for X = H,Cl, Br,I and CH3

The heats of reaction of HMo(CO)₃C₅H₅ with CX₄ (X = Cl, Br) producing XMo(CO)₃C₅H₅ have been measured by solution calorimetry and are −31.8±0.9 and −34.4±2.0 kcal/mole, respectively. The heats of reaction of NaMo(CO)₃C₅H₅ with I₂ and CH₃I producing IMo(CO)₃C₅H₅ and H₃CMo(CO)₃C₅H₅ are −32.3± 1.3 and −7.7± 0.3 kcal/mole. Oxidation with Br₂CCl₄ yielding Br₃Mo(CO)₂C₅H₅ was measured for the following complexes: (C₅H₅(CO)₃Mo)₂, (−92.0±1.0 kcal/mole), BrMo(CO)₃C₅H₅ (−24.9± 2.0 kcal/mole) and HMo(CO)₃C₅H₅ (−60.7± 2.0 kcal/mole). These and other data are used to calculate the Mo–X bond strength for X = H, Cl, Br, I, and CH₃. These bond strength estimates are compared to those reported for X₂Mo(C₅H₅)₂. Iodination of H₃CMo(CO)₃C₅H₅, reported in the literature to yield CH₃I and IMo(CO)₃C₅H₅, actually produces CH₃C(O)I and I₃Mo(CO)₂C₅H₅.     

Special Reactions of α,β-Unsaturated Ketones III [1]. Formation and Structure Elucidation of Dimers of 2-Aryl-methyleneketones: (5E)-5-Benzylidene-9β-phenyl-trans-4a-1,2,3,4,4a,5,6,7,8,9a-decahydroxanthen-4aα-ol and 3β,5β-Bis-(4-methoxyphenyl)-2α,4β,6α-trimethyl-4α-propionyl-cyclohexanone [2]

Summary.  The reaction of 2-benzylidenecyclohexanone and 1-(4-methoxyphenyl)-2-methyl-1-penten-3-one with guanidine did not yield the expected 4-phenylhexahydro-2-quinazolinamine and 4-(p-methoxyphenyl)-dihydro-2-pyrimidinamine, respectively, but nitrogen-free products which turned out as [3+3]- and [4+2]-cycloadducts of two molecules of the applied vinylogous ketone each. According to elemental analyses, mass spectra, and, in particular, NMR analyses (¹H and ¹³CNMR, HH-COSY, gs-HSQC, gs-HMBC, 1D TOCSY, NOESY, and 1D NOE difference spectra), the prepared dimers were identified as racemic (5E)-5-benzylidene-9β-phenyl-trans-4a-1,2,3,4,4a,5,6,7,8,9a-decahydroxanthen-4aα-ol and 3β,5β-bis-(4-methoxyphenyl)-2α,4β,6α-trimethyl-4α- propionylcyclohexanone, respectively. Structure and stereochemistry of the dimers are elucidated, and mechanisms for their formation are proposed. Received April 11, 2001. Accepted (revised) May 18, 2001     

Regio-selective reduction of the C–C double bonds in α,β-unsaturated acyl 4-substituted oxazolidin-2-ones and oxazolidine-2-thiones

Selective saturation of the conjugated C–C double bonds in the title compounds was examined in a systematic way for the first time. Many established protocols effective for similar reduction of α,β-unsaturated ketones and esters in the literature were found to be inapplicable in the present context. The most satisfactory results were finally obtained using the DIBAL-H/MeLi/CuI/HMPA/THF conditions.     

Synthesis, molecular docking and preliminary in-vitro cytotoxic evaluation of some substituted tetrahydro-naphthalene (2',3',4',6'-tetra-O-acetyl-β-D-gluco/-galactopyranosyl) derivatives

A facile, convenient and high yielding synthesis of novel S-glycosides and N-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons 2, 4, and 7 were coupled with different activated halosugars in the presence of basic and acidic medium. The preliminary in-vitro cytotoxic evaluation revealed that compounds 3c, 3f, 5c and 7b show promising activity. A molecular docking study was performed against tyrosine kinase (TK) (PDB code: 1t46) by Autodock Vina. The docking output was analyzed and some compounds have shown hydrogen bond (H-B) formation with reasonable distances ranged from 2.06 A° to 3.06 A° with Thr 670 and Cys 673 residues found in the specified pocket. No hydrogen bond was observed with either Glu 640 nor Asp 810 residues, as was expected from pdbsum.     

An H-phosphonate strategy for the synthesis of 2',3'-dideoxynucleoside triphosphates and homodinucleotides

The triphosphates and homodinucleotides of AZT and d4T have been efficiently synthesized from the corresponding nucleoside 50-H-phosphonate monoesters via the reactive pyridinium phosphoramidate intermediates.     

Key structures in the synthesis of steroid antitumor agents. Methods for upbuilding the 17β-pregnane side chain of 3-methoxy-19-norpregna-1,3,5(10)-trien-20-ones with and without an additional 16α,17α-carbocycle

Russian Chemical Bulletin - Methods for extending the side chain of 20-oxopregnanes were summarized. The possibilities of alkylation of 3-methoxy-19-norpregna-1,3,5(10)-trien-20-one and its...     

(¹⁵N ± ¹³C') edited (4, 3)D-H(CC)CONH TOCSY and (4, 3)D-NOESY HNCO experiments for unambiguous side chain and NOE assignments of proteins with high shift degeneracy

Well-resolved and unambiguous through-bond correlations and NOE data are crucial for high-quality protein structure determination by NMR. In this context, we present here (4, 3)D reduced dimensionality (RD) experiments: H(CC)CONH TOCSY and NOESY HNCO--which instead of (15)N shifts exploit the linear combination of (15)N(i) and (13)C'(i-1) shifts (where i is a residue number) to resolve the through-bond (1)H-(1)H correlations and through-space (1)H-(1)H NOEs. The strategy makes use of the fact that (15)N and (13)C' chemical shifts when combined linearly provide a dispersion which is better compared to those of the individual chemical shifts. The extended dispersion thus available in these experiments will help to obtain the unambiguous side chain and accurate NOE assignments especially for medium-sized alpha-helical or partially unstructured proteins [molecular weight (MW) between 12-15 kDa] as well as higher MW (between 15-25 kDa) folded proteins where spectral overlap renders inaccurate and ambiguous NOEs. Further, these reduced dimensionality experiments in combination with routinely used (15)N and (13)C' edited TOCSY and NOESY experiments will provide an alternative way for high-quality NMR structure determination of large unstable proteins (with very high shift degeneracy), which are not at all amenable to 4D NMR. The utility of these experiments has been demonstrated here using (13)C/(15)N labeled ubiquitin (76 aa) protein.     

Highly ordered thin films of 5,5'-bis(3'-fluoro-biphenyl-4-yl)-2,2' : 5',2'-terthiophene with two meso-phases

The growth process and phase state of 5,5'-bis(3'-fluoro-biphenyl-4-yl)-2,2'?:?5',2'- terthiophene (m-F2BP3T) thin films were investigated by atomic force microscopy (AFM), in-plane and out-of-plane X-ray diffraction (XRD), and selected area electron diffraction (SAED). Two meso-phases (thin film phases) of m-F2BP3T films on SiO(2) surface were obtained in the early stages. The m-F2BP3T films initially exhibited two-dimensional (2D) layers (≤4 ML) followed by three-dimensional (3D) island growth. The film structure evolved two thin film phases in the first four layers and the bulk phase was formed from the fifth layer, which occurred concomitantly with the change of the growth mode. Moreover, the variation of weak epitaxy growth behavior of ZnPc from 2D to 3D growth further reflects that the phase state of the first three layers is different from that of the fourth layer, in spite of ZnPc crystals showing just one orientation corresponding to commensurate epitaxy. The novel phase behavior is closely related to the synergistic effects of the outstanding soft matter properties, limited elasticity of organic molecules, and strain originating from the SiO(2) substrate. This study investigates novel phase behavior in organic thin films and provides significant insight into the mechanism of the phase transition.     

Derivatives of α,β-dehydro amino acids: III. Reaction of 4-arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones with hexamethyldisilazane

4-Arylmethylidene-4,5-dihydro-1,3-oxazol-5-ones reacted with hexamethyldisilazane in ethyl acetate, acetonitrile, or DMF at room temperature to give mainly 2-acylamino-3-arylmethylideneprop-2-enamides, whereas in boiling DMF the corresponding 4-arylmethylidene-4,5-dihydro-1H-imidazol-5-ones were formed. The reaction of 2-benzoylamino-3-phenylprop-2-enamide with hexamethyldisilazane also led to the formation of 4-benzylidene-2-phenyl-4,5-dihydro-1H-imidazol-5-one, while its reaction with chlorotrimethylsilane afforded either a 1:1 mixture of 4-benzylidene-2-phenyl-4,5-dihydro-1,3-oxazol-5-one and 4-benzylidene-2-phenyl-4,5-dihydro-1H-imidazol-5-one or only the latter, depending on the solvent.     

Sodium acetate catalyzed tandem Knoevenagel–Michael multicomponent reaction of aldehydes, 2-pyrazolin-5-ones,and cyano-functionalized C–H acids: Facile and efficient way to 3-(5-hydroxypyrazol-4-yl)-3-aryl-propionitriles

Sodium acetate catalyzed multicomponent reaction of aryl aldehydes, 2-pyrazolin-5-ones, and malononitrile or alkyl cyanoacetates in alcohols results in the formation of substituted 3-(5-hydroxy-3-methylpyrazol-4-yl)-3-arylpropionitriles in 80–99% yields. The developed efficient catalytic approach to the substituted 3-(5-hydroxy-3-methylpyrazol-4-yl)-3-arylpropionitriles – the promising compounds for human cardiovascular diseases therapy and different biomedical applications – is beneficial from the viewpoint of diversity-oriented large-scale processes and represents facile, efficient and environmentally benign synthetic concept for multicomponent reactions strategy.