Ring-Opening Polymerization of ε-Caprolactone and Styrene Oxide–CO2 Coupling Reactions Catalyzed by Chelated Dehydroacetic Acid–Imine Aluminum Complexes

A series of chelated dehydroacetic acid–imine-based ligands L1H~L4H was synthesized by reacting dehydroacetic acid with 2-t-butylaniline, (S)-1-phenyl-ethylamine, 4-methoxylbenzylamine, and 2-(aminoethyl)pyridine, respectively, in moderate yields. Ligands L1H~L4H reacted with AlMe3 in toluene to afford corresponding compounds AlMe2L1 (1), AlMe2L2 (2), AlMe2L3 (3), and AlMe2L4 (4). All the ligands and aluminum compounds were characterized by IR spectra, 1H and 13C NMR spectroscopy. Additionally, the ligands L1H~L4H and corresponding aluminum derivatives 1, 3, and 4 were characterized by single-crystal X-ray diffractometry. The catalytic activities using these aluminum compounds as catalysts for the ε-caprolactone ring-opening polymerization (ROP) and styrene oxide-CO2 coupling reactions were studied. The results show that increases in the reaction temperature and selective solvent intensify the conversions of ε-caprolactone to polycaprolactone. Regarding the coupling reactions of styrene oxide and CO2, the conversion rate is over 90% for a period of 12 h at 90 °C. This strategy dispenses the origination of cyclic styrene carbonates, which is an appealing concern because of the transformation of CO2 into an inexpensive, renewable and easy excess carbon feedstock.

SYNTHESIS AND PROPERTIES OF CHALCONES BASED ON DEHYDROACETIC ACID

The Knoevenagel condensation reaction between dehydracetic acid and aromatic aldehydes is described in this work. The reaction is carried out directly between dehydroacetic acid and aromatic aldehydes in the presence of organic bases. The optimal conditions for the Knoevenagel reaction based on dehydroacetic acid and various aldehydes were determined. Twenty-one chalcones with substituents of different nature were synthesized. The composition and structure of the obtained compounds were determined. All characteristic signals of chalcones are present in the 1H NMR spectra of the obtained compounds registered in CDCl3 and DMSO-d6: OH groups in the range of 18.7–16.5 ppm, CH proton – 6.3–5.9 ppm, and methyl group of the pyran cycle 2.3–2.2 ppm. The corresponding signals of methine protons and aryl substituents are also present in the spectra. The most sensitive to solvent changes is the OH proton bound by an intramolecular hydrogen bond to the carbonyl group of the pyran ring. Signals in DMSO are usually shifted by 0.1–1.0 ppm in a stronger field compared to CDCl3 for dehydroacetic acid and chalcones based on it. CH proton signals are shifted by approximately 0.3 ppm in a weaker field, and the signals of the protons of the methyl group are almost insensitive to the solvent. The optical properties of obtained compounds were investigated in DMF, MeOH, MeCN. The synthesized chalcones absorb light in the visible range 330–490 nm with molar extinction coefficients of 3.5–4.5. The solvatochromic effects for most of them are weak – the position of the maximum changes by less than 10 nm. The electron-donor substituents in the phenyl ring (-NMe2 and -NEt2) shift the absorption ma­ximum bathochromically by almost 100 nm compared to others in all investigated solvents.

Advances in the Arena of 1-(4-hydroxy-6-methyl-2H-pyran-2-on-3-oyl)-3-arylpropenone: Preparation, reactivity and transformations

: The 1-(4-hydroxy-6-methyl-2H-pyran-2-on-3-yl)-3-aryl-2-propenones, chalcone analogs derived from dehydroacetic acid (DHA), play a significant role in synthetic organic chemistry and prove to be an important intermediate for the wealth of multifarious biologically active molecules, especially heterocyclic compounds. The following review is an attempt to compile the transformations of DHA-chalcones to various classes of products.

Design and synthesis of highly oxygenated furo[3,2-c]pyran-4-ones and furo[3,2-c]chromen-4-ones scaffold as potential anticancer and antimicrobial agent

Synthesis of a number of highly oxygenated furo[3,2-c]pyran-4-one (4, 5) and furo[3,2-c]chromen-4-one (8, 9) has been accomplished by a simple one pot reaction from easily available versatile starting materials - dehydroacetic acid and 3-acetyl-4-hydroxycoumarin. All the synthesized molecules were characterized utilizing various spectroscopic techniques and screened for anticancer activity (in vitro) against three Colon (HCT-116, SW-620, HT-24), Lung (A-549), Prostate-(PC-3), Breast-(MCF-7) cell lines. Compounds 5a, 9d, 9f showed good activity against breast MCF-7 cancer cell line having IC50 values 6.9, 2.8, 5.3 µM, respectively. Out of these compound 9d showed better activity against prostate PC-3 cell line with IC50 value 3.8 µM. The synthesized compounds were also studied for potential antibacterial activity (in vitro) using different strains of bacteria (Bacillus subtilis and Staphylococcus aureus -Gram-positive, and Escherichia coli- Gram negative) as well as fungal strains (Aspergillus niger and Candida albicans) using Norfloxacin and Fluconazole as antibacterial and antifungal standard drugs, respectively. The outcome of the antimicrobial screening study showed that compound 9f exhibited promising activity against S. aureus and B. subtilis while 5h showed excellent and 5i and 9b showed better activity against E. coli. The compounds 5c-5e displayed excellent activity against C. albicans and A. niger than Fluconazole.

Modification of insulin amyloid aggregation by Zr phthalocyanines functionalized with dehydroacetic acid derivatives

Amyloid fibrils are widely studied both as target in conformational disorders and as basis for the development of protein-based functional materials. The three Zr phthalocyanines bearing dehydroacetic acid residue (PcZr(L1)2) and its condensed derivatives (PcZr(L2)2 and PcZr(L3)2) as out-of-plane ligands were synthesized and their influence on insulin fibril formation was studied by amyloid-sensitive fluorescent dye based assay, scanning electron microscopy, fluorescent and absorption spectroscopies. The presence of Zr phthalocyanines was shown to modify the fibril formation. The morphology of fibrils formed in the presence of the Zr phthalocyanines differs from that of free insulin and depends on the structure of out-of-plane ligands. It is shown that free insulin mostly forms fibril clusters with the length of about 0.3–2.1 μm. The presence of Zr phthalocyanines leads to the formation of individual 0.4–2.8 μm-long fibrils with a reduced tendency to lateral aggregation and cluster formation (PcZr(L1)2), shorter 0.2–1.5 μm-long fibrils with the tendency to lateral aggregation without clusters (PcZr(L2)2), and fibril-like 0.2–1.0 μm-long structures (PcZr(L3)2). The strongest influence on fibrils morphology made by PcZr(L3)2 could be explained by the additional stacking of phenyl moiety of the ligand with aromatic amino acids in protein. The evidences of binding of studied Zr phthalocyanines to mature fibrils were shown by absorption spectroscopy (for PcZr(L1)2 and PcZr(L2)2) and fluorescent spectroscopy (for PcZr(L3)2). These complexes could be potentially used as external tools allowing the development of functional materials on protein fibrils basis.

Condensation of Lactones with Primary Diamines

The condensation of dehydroacetic acid and 4-hydroxy-6-methylpyran-2-one with primary diamine derivatives such as hydrazine, 1,2-diaminoethane and 1,6-diaminohexane yielded bispyrone and bispyridone derivatives has been reported. The condensation of 4-hydroxy-6-methylpyran-2-one with hydrazine in acetonitrile generated another bispyrazole product but in n-butanol, this reaction afforded the bispyridones. The structures of the synthesized bispyrazoles were examined by spectroscopy and X-ray diffraction analysis, while those of bispyridones were established by spectroscopy data (NMR, mass). Some new complexes were also synthesized in order to show the behaviour of ligands with suitable crystals for X-ray analysis.

Synthesis, spectral and luminescent properties of new alkylamino-beta-ketoenol compounds and metal complexes on their basis for creation of fluorescent probes for biomolecules and optical materials

A series of chalcones and alkylamino-β-ketoenol dyes based on dehydroacetic acid were synthesized in this work. Their individuality is established and physicochemical properties are investigated. A number of phthalocyanine complexes of zirconium and hafnium with these β-ketoenol ligands have been obtained, and their spectral-luminescent properties have been studied. It is established that the obtained complexes absorbs light in a wide spectral range from 300 to 700 nm. Functionalized alkylamino-β-ketoenoles are reported as probes for fluorescent detection of protein aggregates that associated with dangerous diseases, including neurodegenerative disorders. Depending on the nature of the substituents, these dyes can increase the fluorescence intensity tenfold in the presence of fibrillar aggregates, but are practically insensitive to native proteins. The studied dyes have a green-yellow emission in the region of 495–540 nm. For the most effective compound (2E,5Z,7E)-8-(4-(dimethylamino)phenyl)-6-hydroxy-2-(2-methoxyethyl-amino)octa-2,5,7-trien-4-one the fluorescence quantum yield upon binding to insulin fibrils reaches 47.0%, while for the free dye this value is about 0.5%. Due to its sensing properties, this dye exceeds the properties of Thioflavin T, which is the standard for the determination of amyloid fibrils. Alkylamino-β-ketoenol dyes have been shown to be promising as fluorescent probes for the detection of β-pleated protein aggregates.