New Drimane Sesquiterpenes and Polyketides from Marine-Derived Fungus Penicillium sp. TW58-16 and Their Anti-Inflammatory and α-Glucosidase Inhibitory Effects

Marine fungi-derived natural products represent an excellent reservoir for the discovery of novel lead compounds with biological activities. Here, we report the identification of two new drimane sesquiterpenes (1 and 2) and six new polyketides (3–8), together with 10 known compounds (9–18), from a marine-derived fungus Penicillium sp. TW58-16. The planar structures of these compounds were elucidated by extensive 1D and 2D NMR, which was supported by HR-ESI-MS data. The absolute configurations of these compounds were determined by experimental and calculated electronic circular dichroism (ECD), and their optical rotations compared with those reported. Evaluation of the anti-inflammatory activity of compounds 1–18 revealed that compound 5 significantly inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells, correlating with the inhibition of expression of inducible nitric oxide synthase (iNOS). In addition, we revealed that compounds 1, 3–6, 14, 16, and 18 showed strong α-glucosidase inhibitory effects with inhibition rates of 35.4%, 73.2%, 55.6%, 74.4%, 32.0%, 36.9%, 88.0%, and 91.1%, respectively, which were comparable with or even better than that of the positive control, acarbose. Together, our results illustrate the potential of discovering new marine-based therapeutic agents against inflammation and diabetes mellitus.

Systemic Review of Screening the Shapes of Ibuprofen Particles in Different Solvents

Ibuprofen is a very popular analgesic which is mostly available in the market as tablet dosage form. The ibuprofen molecule possesses a chiral center in the propionic acid group. So, there are two enantiomers (R and S), whose chemical properties are similar, but which have optical rotations of opposite sign. The (-) form (l- or laevo-) is the R (-) enantiomer whereas the (+) form (d or dextro-) is referred to as S (+) – ibuprofen. The R (-) isomer is biologically inactive while the S (+) isomer is active. The R (-) form however is slowly converted to the S (+) active form during metabolism in the human body by the presence of the enzyme isomerase (2-arylpropionyl-CoA epimerase). Thus, a large difference in the body potency between the two enantiomers is not found. During manufacturing of tablet, ibuprofen particle plays a significant role in flowability and compressibility etc. Theoretically particle size and shape have great impact on those sorts of mechanical properties of tablets. The morphology can influence physical properties such as packing density, bulk density, agglomeration, and dissolution behaviour as well as the mechanical strength and wet ability. Furthermore, crystal shapes have also been found to have an effect on the bioavailability of the resulting APIs. Commercial ibuprofen typically has a needle shaped morphology with rough surfaces and show poor flowability, poor compaction behavior and a tendency to stick to the tablet punches. To overcome these problems, a suitable size and shape of ibuprofen crystal is desirable that could be directly compressed with fewer operation steps but still having good product stability and therapeutic efficacy, but it can be changed through recrystallization or other methods such as spray drying, etc. Ibuprofen crystallized from solvents with a high hydrogen bonding ability like methanol will form chunky crystals and low hydrogen bonding solvents like hexane will form needle like crystals. Therefore, it was necessary to review the shapes of ibuprofen particles in different solvents. This review paper has covered a comprehensive studies of ibuprofen particle shapes in different solvents and cosolvents.

Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.

Antimicrobial Meroterpenoids and Erythritol Derivatives Isolated from the Marine-Algal-Derived Endophytic Fungus Penicillium chrysogenum XNM-12

One new meroterpenoid-type alkaloid, oxalicine C (1), and two new erythritol derivatives, penicierythritols A (6) and B (7), together with four known meroterpenoids (2–5), were isolated from the marine algal-derived endophytic fungus Penicillium chrysogenum XNM-12. Their planar structures were determined by means of spectroscopic analyses, including UV, 1D and 2D NMR, and HRESIMS spectra. Their stereochemical configurations were established by comparing the experimental and calculated electronic circular dichroism (ECD) spectra for compound 1, as well as by comparison of the optical rotations with literature data for compounds 6 and 7. Notably, oxalicine C (1) represents the first example of an oxalicine alkaloid with a cleaved α-pyrone ring, whereas penicierythritols A (6) and B (7) are the first reported from the Penicillium species. The antimicrobial activities of compounds 1–7 were evaluated. Compounds 1 and 6 exhibited moderate antibacterial effects against the plant pathogen Ralstonia solanacearum with minimum inhibitory concentration (MIC) values of 8 and 4 μg/mL, respectively. Compound 6 also possesses moderate antifungal properties against the plant pathogen Alternaria alternata with a MIC value of 8 μg/mL.

Highly effective synthesis of dibromide of (+)-(1R, 2R)-and (-)-(1S, 2S) -1,2- diphenyl-1,2-ethylenediammonium (DPEN∙2HBr) assisted by microwave

Abstract:: In this work, the chiral salts (R,R)- and (S,S)-dibromide of 1,2-diphenyl-1,2-ethylenediammonium (R,R)-9 and (S,S)-9 were synthesized, both by conventional and microwave heating, obtaining yields and optical rotations (c 0.43, H2O) of 92%, +17.48° and 90%, -17.50°, respectively (conventional heating by 24 h) and 92%, +17.52° and 89%, -17.44°, respectively (microwave heating by 1.4 h). These compounds were synthesized by means of the racemic intermediate (±)- iso-amarine (±)-6, leading to the separation of their enantiomers, by fractional optical resolution and using as resolution agents the enantiomers of (+)-(S)- and (-)-(R)-MA 3. The starting reagents were benzaldehyde and 28-30% NH4OH, which are economical and commercially affordable. All synthesized compounds were characterized by melting point, solubility, UV-vis, FT-IR (ATR). Imidazoline (±)-6 and salts (R,R)-9 and (S,S)-9 were additionally characterized by 1H and 13C NMR. Polarimetry was determined to (R,R)-(+)-6, (S,S)-(-)-6, (S,R,R)-(+)-7, (R,S,S)-(-)-7, (S,S)-(+)-8, (R,R)-(-)-8, (R,R)-(+)-9 and (S,S)-(-)-9 compounds.

Polarimetric studies of L-arginine-doped potassium dihydrogen phosphate single crystals

Conoscopic interference patterns, channelled spectra and polarimetric techniques have been used for the characterization of pure and doped (with L-arginine amino acid) potassium dihydrogen phosphate (KDP) single crystals. Experimental polarimetric data have been obtained for the frequently used wavelength of 633 nm and for two close wavelengths of 532 and 543 nm in a high-accuracy dual-wavelength polarimeter. The measurement of eigenwave ellipticity in the [100] and [010] directions and between 295 and 340 K shows small differences in the absolute values of the specific optical rotations of KDP crystals doped with L-arginine in the range of 0.7–3.8 wt%. It is found that the gyration tensor component g 11, specific optical rotation and eigenwave ellipticity show different dispersion in the visible spectral region.

Synthesis and Aggregation-Induced Emission Feature of Series of Polysiloxanes Containing Triphenylpyrrole Side-Chain

A series of aggregation-induced emission (AIE) active polysiloxanes (P7-1~P7-2, P29-1~P29-6) were prepared through hydrosilylation between polymethylhydrosiloxane (PMHS, DP=7 or 29) and AIE-active vinyl monomer 1-(4'-allyloxy-biphenyl)-2,5-diphenyl pyrrole (M-TPP), or with optical active monomer cholesteryl allyloxy ether (M-Chol*). Monomer M-TPP and all of the polymers exhibits aggeragation-induced emission enhancement properties. The fluorescence intensity of M-TPP in THF/H2O mixtures increases when the water fraction is higher than 60%, while is over 20% for polysiloxanes, which mainly because the entanglement of the flexible polysiloxane main-chain can restrict the molecular motion of triphenylpyrrole (TPP) derivates and induce the increasing of the fluorescence intensity. Moreover, the maximum relative fluorescence intensity (I/I0) is equal to 4 for M-TPP and 1.4~4.9 for polysiloxanes, and the grafted degree of the TPP derivative has effect on the AIE properties of polymers. The specific optical rotations of the chiral polymers increase with increasing the content of chiral cholesteryl ether moieties. All the target polymers possess good thermal stabilities and their decomposition points (Td) are greater than 320°C.

Physico-chemical Properties of Nutmeg (Myristica fragrans houtt) of North Sulawesi Nutmeg

Essential oil of nutmeg (Myristica fragrans houtt) is one of the many potentials of nutmeg that has a high economic value although in North Sulawesi it has not been exploited to its full potential. This research was conducted to compare the yield and properties of Nutmeg oil extract from the seeds and mace of Talaud and North Minahasa-North Sulawesi. The oil extract was obtained by distillation and was further characterized in terms of color, solubility in ethanol, density, optical rotation, refractive index. Results of this research exhibited that oil of the mace of nutmeg from Talaud had a lighter appearance in color compared to that from North Minahasa, while the density of oil extracted from North Minahasa was more densed compared to Talaud in both seed and mace (0.923 and 0.938 respectively at 25°C). The reflective index of nutmeg oil from North Minahasa was slightly higher than of Talaud both from seed and mace (1.4834 and 1.493 at 25°C), while the optical rotations of oil extracted from the mace were between +6.90° to +9.80° and from the seed were +20.73° to +22.30°.