Stereoelectronic Features of a Complex Ketene Dimerization Reaction

The amidation reaction of a tetrahydroisoquinolin-1-one-4-carboxylic acid is a key step in the multi-kilogram-scale preparation of the antimalarial drug SJ733, now in phase 2 clinical trials. In the course of investigating THIQ carboxamidations, we found that propanephosphonic acid anhydride (T3P) is an effective reagent, although the yield and byproducts vary with the nature and quantity of the base. As a control, the T3P reaction of a 3-(2-thienyl) THIQ was performed in the absence of the amine, and the products were characterized: among them are three dimeric allenes and two dimeric lactones. A nucleophile-promoted ketene dimerization process subject to subtle steric and stereoelectronic effects accounts for their formation. Two novel monomeric products, a decarboxylated isoquinolone and a purple, fused aryl ketone, were also isolated, and mechanisms for their formation from the ketene intermediate are proposed.

Physicochemical Properties and Digestion Resistance of Acetylated Starch Obtained from Annealed Starch

One of the examples of physical starch modifications is the retention of a starch suspension in water having a temperature slightly lower than the pasting temperature (annealing). The aim of this study was to investigate the effect of the annealing process performed at various temperatures as the first stage of starch modification. The annealed starch preparations were then esterified using acetic acid anhydride. Finally, the annealed and acetylated starch preparations were determined for their properties. The annealing of starch before acetylation triggered changes in the properties of the modified preparations. It contributed to a higher degree of starch substitution with acetic acid residues and to the increased swelling power of starch. Both these properties were also affected by the annealing temperature. The highest resistance to amylolysis was found in the case of the starch preparation annealed at 53.5 °C and acetylated. The double modification involving annealing and acetylation processes increased the onset and end pasting temperatures compared to the acetylation alone. Similar observations were made for the consistency coefficient and yield point.

Phytopharmacognostical and Chromatographic Evaluation of Leaves of Launaea procumbens

Launaea procumbens leaves are galactagogue, diuretic, antifungal, anorexic, anti-arthritic and hepatoprotective according to Ayurvedic texts as well as modern research. Launaea species, particularly L. pinnatifida, is mentioned as one of the sources of Gojihva, regarding which there is controversy with respect to its true botanical identity. However, no detailed anatomical, phytochemical or chromatographic investigation is available for leaf of L. procumbens which can differentiate it from L. pinnatifida. The aim of this work is to develop standardization parameters of L. procumbens leaves by performing its pharmacognostical evaluation, preliminary phytochemical screening, HPTLC and GC-MS fingerprints. Pharmacognostic investigation of the leaves was performed by its morphological study, qualitative and quantitative microscopy as well as powder microscopy. Extraction of leaves was done by maceration using methanol. This extract was used for preliminary phytochemical screening and chemoprofiling by GC-MS, as well as for developing its HPTLC fingerprint. A mobile phase system was developed by pilot TLC, following which an HPTLC fingerprint was performed using the solvent system chloroform: methanol: ethyl acetate (3:7:6). Diagnostic microscopic characters identified in powder include unicellular covering trichome, xylem vessels, anomocytic stomata, and prisms of calcium oxalate crystal. Phytochemical screening revealed the presence of phytoconstituents classes like phenolics, anthraquinones, saponin glycosides, carbohydrates, sterols, triterpenoids and flavonoids. HPTLC fingerprinting detected 6 peaks with Rf 0.25, 0.37, 0.41, 0.50, 0.65, 0.78 at 254nm and 4 peaks with Rf 0.32, 0.37, 0.50, 0.66 at 366nm. GC-MS fingerprint revealed presence of propanoic acid anhydride, valeric anhydride, 2- Pyrrolidine acetic acid, phthalan, 5- (Hydroxy methyl)-2-(dimethoxy methyl) furan, vanillin, methyl β-l-Arabino pyranoside, 1,6-anhydro-β-D-Gluco pyranose and 6-Methyl-2-Heptanone, 6-(3,5-dimethyl-2-furanyl). Present study will be very useful for herbal industry in differentiating Launaea procumbens from other species of the genus Launaea, particularly L. pinnatifida (Gojihva) as well as for authentication, standardization and detection of adulteration in the leaf formulations of Launaea procumbens.

Design of antigen synthesis and identification of its artificial antigen for zearalenone

Background: study aimed to modify the ZEN molecule and conjugate the carrier protein to prepare a complete antigen. To lay the foundation for the preparation of ZEN monoclonal antibodies. Methods: The carbonyl group at the 7 position of ZEN molecule was modified by deuteration reaction. The immunogen and antigen were synthesized by EDC method and mixed acid anhydride method, and the complete antigen was identified by UV, IR and electrophoresis. Antisera were obtained after immunization of animals, and an antiserum was designed by ELISA. Results: The immunogens were identified by UV, IR and electrophoresis, ZEN-BSA was successfully synthesized. The ratio of ZEN-BAS to ZEN was calculated to be 1 : 13. When the antibody serum was detected, the titer of the antibody reached 1:(6.4×103). Conclusion: This study demonstrated that the OAE method is preferable in preparing the ZEN. These findings lay the material and technical foundation for the preparation of anti-ZEN monoclonal antibody

CryoEM structure of the antibacterial target PBP1b at 3.3 Å resolution

The pathway for the biosynthesis of the bacterial cell wall is one of the most prolific antibiotic targets, exemplified by the widespread use of β-lactam antibiotics. Despite this, our structural understanding of class A penicillin binding proteins, which perform the last two steps in this pathway, is incomplete due to the inherent difficulty in their crystallization and the complexity of their substrates. Here, we determine the near atomic resolution structure of the 83 kDa class A PBP from Escherichia coli, PBP1b, using cryogenic electron microscopy and a styrene maleic acid anhydride membrane mimetic. PBP1b, in its apo form, is seen to exhibit a distinct conformation in comparison to Moenomycin-bound crystal structures. The work herein paves the way for the use of cryoEM in structure-guided antibiotic development for this notoriously difficult to crystalize class of proteins and their complex substrates.

Propylphosphonic acid anhydride–mediated amidation of Morita–Baylis–Hillman–derived indolizine-2-carboxylic acids

Propylphosphonic acid anhydride has been successfully used as a coupling agent in the synthesis of a series of indolizine-2-carboxamido derivatives from indolizine-2-carboxylic acid and its 3-acetylated analogue. The acid substrates were obtained by saponification of the corresponding methyl esters produced, in turn, selectively and efficiently, by time-controlled cyclisation of a single Morita–Baylis–Hillman adduct. Various amino and hydrazino compounds with medicinal potential have been used to prepare indolizine-2-carboxamido and hydrazido derivatives.

The crystal structure of benzeneseleninic acid anhydride, C12H10O3Se2

C12H10O3Se2, triclinic, P 1 ‾ $‾{1}$ (no. 2), a = 9.1794(3) Å, b = 11.5706(5) Å, c = 12.3976(5) Å, α = 85.291(2)°, β = 72.198(2)°, γ = 74.084(2)°, V = 1205.65(8) Å3, Z = 4, R gt (F) = 0.0275, wR ref (F 2) = 0.0698, T = 200 K.

Innovative technologies in corrosion-resistant coatings development aimed at ship navigation equipment protection

The efficient use of some innovative technologies in adhesives with advanced operational characteristics development aimed at anti-corrosion properties increase of transport means has been substantiated in the paper under discussion. The above-mentioned technologies involving the use of some interaction-active ingredients forming the cross-linkable coatings composition, including some polymers, have provided their cohesion properties essential improvement. Epoxy diane oligomer ED-16 has been chosen as the main component for the matrix in the composite formation. The aliphatic resin DЕG-1 (GOST 10136-77) as a plasticizer has been added to the epoxy oligomer. The compound has been formed of the following concentration: epoxy resin ED-16: plasticizer DЕG -1 – 100: 40. The hardener of cold hardening polyethelenepolyamine PEPA (ТУ 6-05-241-202-78) has been used at the epoxy resin-based developed materials polymerization. Phthalic acid anhydride has been used as a modifier to improve the properties of epoxy composite materials. The modifier was added to the matrix in the following ratio: from 0,10 to 2,00 pts.wt. per 100 pts.wt. of epoxy oligomer ЕD-20. The molecular formula of the modifier is as follows: C8H4O3. Molar mass is 148,1 g/mol. Density is ρ = 1,52 г/см³. To form a composite material or a protective coating with some improved adhesive properties and inconsiderable residual stresses the phthalic acid anhydride as a modifier was found to be added to the epoxy matrix with the content q = 1,25 pts.wt. per 100 pts.wt. of the epoxy matrix (oligomer ЕD-20 + plasticizer DЕG -1). In this case, the adhesive strength of the coating is being increased from sа = 28,3 MPа to sа = 46,4 MPа, and residual stresses – from sз = 1,9 MPа to sз = 2,1 MPа. First of all, the improved properties of the modified materials were caused by the interaction of active carbonyl (С=О) groups of the modifier with nitrogen-containing (NH-) groups of the hardener. It has provided the increase of the composite cross-linking degree resulted in their both adhesive and cohesion properties improvement. Moreover, it was found that the modifier use in the compound with the content q = 1,0…1,5 00 pts.wt. per 100 00 pts.wt. of the matrix has provided the increase of the river water influenced coatings resistance from ρ = 12,1 Оm·cm2 до ρ = 21,2…22,4 Оm·cm2. Though, some further increase of the additive content in the coating has caused the deterioration of anti-corrosion characteristics of the materials. Thus, the conducted study has contributed to the determination of the most efficient content ratio of phthalic acid anhydride as a modifier to for the coatings of functional use.

Synthesis of a Potent Pan-Serotype Dengue Virus Inhibitor Having a Tetrahydrothienopyridine Core

A synthesis of the first-in-class pan-serotype dengue virus inhibitor NITD-688 is presented. The Gewald reaction of N-(tert-butoxycarbonyl)-6,6-dimethylpiperidin-3-one with malononitrile and sulfur in the presence of l-proline as a catalyst gave tert-butyl 2-amino-3-cyano-6,6-dimethyl-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate. This was coupled with [4-(aminosulfonyl)phenyl]acetic acid by using propane­phosphonic acid anhydride. A subsequent reductive alkylation with cyclohexanecarboxaldehyde gave NITD-688. Preliminary results of our attempts to control the regioselectivity of the Gewald synthesis of the 2-amino-3-cyanothiophene core are also presented.