Letters in Organic Chemistry - Volume 17, Issue 2, 2020

Maltodextrins have an increasing number of biomedical and industrial applications due to their attractive physicochemical properties such as biodegradability and biocompatibility. Herein, we describe the development of a synthetic pathway and characterization of thiol-responsive maltodextrin conjugates with dithiomaleimide linkages. 19F NMR studies were also conducted to demonstrate the exchange dynamics of the dithiomaleimide-functionalized sugar end groups.

Di(2-ethylhexyl) phthalate (DEHP) is the most common phthalate ester, which has been used as a plasticizer for the production of numerous polymers, particularly polyvinyl chloride (PVC). Many other groups have synthesized meso-DEHP indicating interest in this molecule, but we are the first to synthesize enantiomerically pure di[(R)-2-ethylhexyl] phthalate. We report herein, for the first time, the isolation - from the cultures of Bacillus thuringiensis, B. subtilis, and B. velezensis strains - of di[(R)-2-ethylhexyl] phthalate, enantiomerically pure and in good yields: its biological activity against bacteria and fungi was probed and for the first time its synthesis was done.

A novel bis-indole alkaloid was isolated from the flowers of Rauvolfia Yunnanensis Tsiang. Its structure was elucidated as 10,11´- dimethoxy-11,10´-bis-[N(a)-methyl deacetyldeformyl- 1,2- dihydro akuammiline(2β)] (1) on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as HRESI-MS and comparison with data from the literature. The bis-indole alkaloid displayed more potent antihypertension activity and much lower hepatotoxicity in vivo than Reserpine.

Calix[4]monoquinone (3) has been synthesized by oxidation of rigid cone conformation of tripropoxy calix[4]arene (2), and conformational characteristics of this molecule have been studied by means of dynamic nuclear magnetic resonance (DNMR) and HH- correlated nuclear magnetic resonance spectroscopy (HH-COSY NMR). On the basis of the data that have been obtained, free Gibbs energy of activation (ΔG#) for quinone ring interconversion process of 3 was determined 12.3±0.05 Kcal/mol by coalescence approximation method.

Titanium ethoxide has been employed as a novel and efficient reagent for the Knoevenagel condensation of aldehydes with active methylenes such as diethyl malonate and ethyl cyanoacetate under solvent free conditions to afford substituted olefins in high to excellent yields. The reaction is suitable for a variety of aromatic, aliphatic and heteroaromatic aldehydes with various active methylenes. Parallel to this, microwave irradiation has been utilized to achieve improved reaction rates and enhanced yields. Herein, we illustrated a convenient method for the preparation of α,β-unsaturated compounds using both conventional and microwave irradiation methods. An efficient and solvent free Knoevenagel condensation between aldehydes and active methylenes was developed using titanium ethoxide. The procedure proved to be successful with a wide range of substrates such as aromatic, aliphatic and heterocyclic aldehydes and various active methylenes to afford substituted olefins. The reaction was also carried out under microwave irradiation to accomplish the corresponding olefins with improved reaction rates, yields and cleaner reaction profiles.We have developed an efficient and novel methodology for the synthesis of olefinic compounds by Knoevenagel condensation under solvent-free conditions using titanium ethoxide, for the first time, as a reagent as well as a solvent. This method is appropriate for the synthesis of a variety of aromatic aldehydes containing various electron-donating and withdrawing groups, aliphatic and heteroaromatic aldehydes. The significant advantages offered by this methodology could be applied to various active methylenes in order to offer the corresponding Knoevenagel products. Thus, we believe that this method delivers high conversions, cleaner reaction profiles under solvent-free reaction conditions and shorter reaction times, all of which make it a very useful and attractive approach for the preparation of a wide range of substituted olefins.

Hypoxylon sp. was used to ferment at 25°C for 45 days. The solid culture of Hypoxylon sp. was extracted with 75% EtOH under ultrasonic for twice. And the dried combined extracts were then suspended in H2O and partitioned with ethyl acetate. EtOAc extracts were subjected to a silica gel column and eluted with petroleum ether - acetone to afford seven fractions. Sephadex LH-20 and RPHPLC were used subsequently to yield a novel xanthone metabolite (Hypoxylon xanthone A). Its structure was elucidated based on HR-ESI-MS, 1D-, 2D-NMR spectra, and the comparison of the experimental and calculated ECD spectra. The anti-neuroinflammatory assay of Hypoxylon xanthone A, as manifested by the inhibitory effect on LPS-induced NO production in BV-2 microglial cells, indicated almost the same inhibitory effect as minocycline in a dose-dependent manner within the concentration of 1-50 μM, suggesting that Hypoxylon xanthone A could be a new potential neuroinflammation inhibitor.

The aim of the current article was to describe simple procedures for the synthesis of new heterocycles incorporating the quinoxaline moiety using benzene-1,2-diamine and quinoxaline-2,3- dithiol as precursors. Simple synthetic methods are described for the synthesis of new heterocycles using commercially available chemicals. Also, the new compounds were determined using analytical and spectroscopic methods including single X-ray crystal structures. A series of new heterocycles containing the quinoxaline nucleus have been synthesized in good yields using simple and convenient procedures. A process has been described for the synthesis of new heterocycles containing the quinoxaline moiety that might be difficult to synthesize by other routes.

A K2CO3 promoted efficient one pot two-step method for the preparation of 1H-imidazol-4- yl-1-amine derivatives has been developed. A series of second amines with an imidazole group were obtained with 56%-91% yields by the K2CO3 promoted amination of acetates and nitrogen deprotection of the imidazole process.

Oxadiazoles are an important class of heterocyclic compounds, having broad-spectrum activity. They were also reported as anticancer, and antioxidant agents, hence it is of significant importance to explore new oxadiazoles. A series of eleven (5-aryl-N-[4-(trifluoromethyl)phenyl]-1,3,4- oxadiazol-2-amines (6a-k) was synthesized based on the structures of reported compounds, SU-101, IMC38525, and FTAB. All these oxadiazoles were synthesized, characterized by spectral data, and further tested against melanoma, leukemia, colon, lung, CNS, ovarian, renal, breast and prostate cancer cell lines’ panels at a single dose of 10 μM drug concentrations. N-(4-(Trifluoromethyl)phenyl)-5-(3,4- dimethoxyphenyl)-1,3,4-oxadiazol-2-amine (6h) showed significant anticancer activity, and the most sensitive five cell lines were NCI-H522 (% GI = 53.24), K-562 (% GI = 47.22), MOLT-4 (% GI = 43.87), LOX-IMVI (% GI = 43.62), and HL-60(TB) (% GI = 40.30). The compound, 6h revealed better %GIs than imatinib, against 36 cell lines, taking 54 cell lines in common. The maximum sensitivity was recorded against cancer cell line CCRF-CEM (% GI = 68.89) by 2-(5-(4-(trifluoromethyl) phenylamino)-1,3,4-oxadiazol-2-yl)phenol (6f). The antioxidant activity of 4-(5-(4-(trifluoromethyl) phenylamino)-1,3,4-oxadiazol-2-yl)-2-methoxyphenol (6i) was promising with an IC50 of 15.14 μM. It was observed that the oxadiazoles reported herein showed significant anticancer and antioxidant activities.

The present study deals with the synthesis of novel 1-(1,3-benzothiazol-2-yl)-3-chloro-4Hspiro[ azetidine-2,3'-indole]-2',4(1'H)-dione derivatives from the reaction of 3-(1,3-benzothiazol-2- ylimino)-1,3-dihydro-2H-indol-2-one derivatives with chloroacetyl chloride in the presence of triethylamine (TEA). The mechanism involved simple acid or base catalysed reaction through the formation of Schiff base followed by cyclisation via ketene–imine cycloaddition reaction. All synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. The antimicrobial activities of the synthesized derivatives 5a-5g were examined via Micro Broth Dilution method against bacterial strains Bacillius subtilis, Staphylcoccus aureus, E. coli, P. aeruginosa, and fungal strain Candida albicans for determining MIC values. Ampicillin, chloramphenicol, and griseofulvin were used as standard drugs. The MIC values for antimicrobial activity of synthesized compounds were examined using Micro Broth Dilution method. Compounds 5a, 5b, and 5c were found effective against E. coli (MTCC 442) and P.aeruginosa (MTCC 441) and all compounds showed moderate to excellent activity against Streptococcus aureus (MTCC 96) and Bacillius subtilis (MTCC 441). Regarding the antifungal screening, compounds 5a, 5b, and 5c exhibited excellent activity against Candida albicans MTCC 227. 1-(1,3-benzothiazol-2-yl)-3-chloro-4H-spiro[azetidine-2,3'-indole]-2',4(1'H)-dione derivatives may be used as potential lead molecules as effective antimicrobial agents.

A series of novel 2-S-, 4-, 5-substituted and bicyclic 6-methylpyrimidine-4-ol derivatives including pyrazole, 1,2,4-triazole and pyridazine moieties in the molecule were synthesized by accessible and efficient methods. Thiopyrazolyl derivatives were obtained from 2-mercapto-6-methylpyrimidin-4-ol. 4-Triazolyl and 4-aminotriazolylpyrimidines were synthesized from the quaternary ammonium salt of pyrimidine and 4-chloro-substituted 2-thiomethyl-6-methylpyrimidine, respectively. The reaction of potassium salt of 1-methyl-6-oxo-1,6-dihydropyridazin-3-ole with ethyl 2-chloro-3-oxobutanoate and subsequent treatment with thiourea led to 6-((4-hydroxy-2-mercapto-6-methylpyrimidin-5-yl)oxy)-2- methylpyridazin-3 (2H)-one. The reaction product of the latter with 3-chloropentan-2,4-dione was subjected to heterocyclization, which afforded the target bicyclic derivative of pyrimidine. The synthesized compounds showed a pronounced stimulating action on plants growth. Their growth stimulant activities were in the range of 60-93% compared to heteroauxin.

We have developed an efficient and green synthesis of quinoline derivatives using L-proline under Knoevenagel condensation. L-proline was found to be an efficient catalyst for the Knoevenagel condensation of substituted 2-aminoaryl ketones 1 with the active methylene compounds 2, affording quinolone derivatives 3. The reaction has been done under conventional as well as under microwave conditions. The latter procedure has been found to be much more efficient in terms of time and yield.