Synthesis of (−)-okundoperoxide and determination of the absolute configuration of natural (+)-okundoperoxide

The first enantioselective synthesis of (3S,4aR,8aR)-1 (the enantiomer of natural okundoperoxide) has been accomplished. The synthesis features: 1) stereoselective installation of the peroxy functionality (16 → 17); 2) ring opening of peroxyacetal and subsequent intramolecular reaction between the hydroperoxide and the vinyl epoxide to form the peroxy six-membered ring (5 → 1). The absolute configuration of okundoperoxide was determined to be 3R,4aS,8aS by comparing specific rotations of the synthetic sample and the natural product.     

Biotransformation of 3-azidomethyl-4-phenyl-3-buten-2-one and analogs by Saccharomyces cerevisiae: New evidence for an SN2′ mechanism

(Z)-3-XCH₂-4-(C₆H₅)-3-buten-2-one enones (X = SCN, N₃, SO₂Me, OC₆H₅) were synthesized and submitted to biotransformations using whole Saccharomyces cerevisiae cells. The enone (X = SCN) produced (R)-4-(phenyl)-3-methylbutan-2-one (R)-6 with 93% ee and enones (X = N₃, SO₂Me, OC₆H₅) yielded a mixture of (R)-6 and the corresponding CC bond reduction products. Biotransformation with enone (X = N₃) mediated by Saccharomyces cerevisiae resulted in two products via two different routes: (i) the ketone (R)-4-azido-3-benzylbutan-2-one in 28% yield and with >99% ee by CC bond reduction; (ii) ketone (R)-6 in 51% yield and with 95% ee via cascade reactions beginning with azido group displacement by the formal hydride from flavin mononucleotide in an S_N2′ type reaction followed by reduction of the newly formed CC bond.     

Diterpenoids from the aerial parts of Leonurus macranthus

One cis clerodane-type (1) and three highly oxygenated labdane-type diterpenes (2-4) were isolated from the aerial parts of Leonurus macranthus. Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus.     

Palladium-catalyzed domino sequence for the synthesis of N-aryl quinolinone-3-carboxylate derivatives and their anti-proliferative activity

An efficient and an operationally simple Palladium-catalyzed domino reaction for the synthesis of N-aryl quinolinone-3-carboxylate derivatives has been developed via the reaction between diethyl 2-(2-bromobenzylidine) malonate and anilines. These newly synthesized compounds exhibited good to moderate anti-proliferative activity with GI₅₀ values ranging from 0.41 µM to 45.77 µM. Among them, compounds 6j, 6k and 6m demonstrated potential activity particularly against MCF-7 (breast) and KB (oral) cancer cell lines.     

Co-crystal of (R,R)-1,2-cyclohexanediol with (R,R)-tartaric acid,a key structure in resolution of the (±)-trans-diol by supercritical extraction,and the related ternary phase system

A novel co-crystal of trans-(R,R)-1,2-cyclohexanediol and (R,R)-tartaric acid (with 1:1 molar ratio, 1) has been found to be a key crystalline compound in the improved resolution of (±)-trans-1,2-cyclohexanediol by supercritical fluid extraction. The molecular and crystal structure of this co-crystal, which crystallizes in orthorhombic crystal system (space group P2₁2₁2₁, a = 6.7033(13) Å, b = 7.2643(16), c = 24.863(5), Z = 4), has been solved by single crystal X-ray diffraction (R = 0.064). The packing arrangement consists of two dimensional layers of sandwich-like sheets, where the inner part is constructed by double layers of tartaric acids which hydrophilicity is “covered” on both upper and bottom side by cyclohexanediols with the hydrophobic cyclohexane rings pointing outward. Thus, a rather complex hydrogen bonding pattern is constructed. The relatively high melting point (133 °C) observed by both simultaneous TG/DTA and DSC, and the main features of FTIR-spectrum of 1 are explained by the increased stability of this crystal structure. DSC studies on binary mixtures of co-crystal 1 with (R,R)-1,2-cyclohexanediol or (R,R)-tartaric acid, revealed eutectic temperatures of T_eu = 100 or 131 °C, respectively. Between (S,S)-1,2-cyclohexanediol and (R,R)-tartaric acid a eutectic temperature of T_eu = 85 °C have also been observed. The phase relations have been confirmed by powder X-ray diffraction, as well.     

Synthesis,spectral characterization,theoretical, antimicrobial,DNA interaction and in vitro anticancer studies of Cu(II) and Zn(II) complexes with pyrimidine-morpholine based Schiff base ligand

Novel Cu(II) (1) and Zn(II) (2) complexes with 4-(1-(4-morpholinophenyl)ethylideneamino)pyrimidine-5-carbonitrile) (L) have been synthesized and characterized by various spectroscopic and analytical techniques. DFT (density functional theory) studies result confirms that, LMCT mechanism have been done between L and M(II) ions. The antimicrobial studies indicate that the ligand L and complexes 1 & 2 exhibit higher activity against the E. coli bacteria and C. albicans fungi. The groove binding mode of ligand L and complexes 1 & 2 with CT-DNA have been confirmed by electronic absorption, competitive binding, viscometric and cyclic voltammetric studies. The electronic absorption titration of ligand L and complexes 1 & 2 with DNA have been carried out in different buffer solutions (pH 4.0, 7.0 & 10.0). The K_b values of ligand L and complexes 1 & 2 are higher in acidic buffer at pH 4.0 (K_b = 2.42 × 10⁵, L; 2.8 × 10⁵, 1; 2.65 × 10⁵, 2) and the results revealed that, the interaction of synthesized compounds with DNA were higher in the acidic medium than basic and neutral medium. Furthermore, CT-DNA cleavage studies of ligand L and complexes 1 & 2 have been studied. The in vitro anticancer activities results show that complexes 1 & 2 have moderate cytotoxicity against cancer cell lines and low toxicity on normal cell line than ligand L.     

Hybrid inorganic–organic frameworks containing magnesium: Synthesis and structures of magnesium squarate,diglycolate, and glutarate,and potassium magnesium cyclobutanetetracarboxylate

Four new magnesium containing metal–organic hybrid compounds have been synthesized in an effort to prepare low-density materials for hydrogen storage. The compounds were prepared hydrothermally and characterized using single crystal X-ray diffraction. Three of these compounds are analogs of known transition metal structures with squarate (I, Pn-3n, a = 16.276(5) Å), diglycolate (II, P2₁2₁2₁, a = 6.860(1) Å, b = 9.993(1) Å, c = 10.884(1) Å, R₁ = 0.0341), and glutarate (III, R-3, a = 10.744(2) Å, c = 28.677(5) Å, R₁ = 0.0554) ligands; the fourth is a novel structure using cyclobutanetetracarboxylate (IV, Pccn, a = 9.382(1) Å, b = 14.410(2) Å, c = 8.725(1) Å, R₁ = 0.0465) which contains potassium as well as magnesium cations.     

Synthesis and crystal structure of (S)-pindolol

Racemic 3-(4-indolyloxy)-1,2-propanediol 2 has been effectively resolved into (S)- and (R)-enantiomers by a preferential crystallization procedure. Non-racemic (S)-2 was converted into (S)-4-(2,3-epoxypropoxy)-1H-indole (S)-4 via a Mitsunobu reaction and then into (S)-pindolol (S)-1. The crystalline (S)-1 was studied by single crystal X-ray diffraction. A large number of symmetry independent molecules (Z′ = 6) led to a weakening of the system of strong intermolecular hydrogen bonds, which combined with a loose packing (PI = 64.6%), may be the cause of the abnormally low melting point of (S)-1 as compared with rac-1.     

Batch and in-flow kinetic resolution of racemic 1-(N-acylamino)alkylphosphonic and 1-(N-acylamino)alkylphosphinic acids and their esters using immobilized penicillin G acylase

The kinetic resolution of racemic 1-(N-acylamino)alkylphosphonic acids 3 (R³ = OH) and their dimethyl esters 1, as well as 1-(N-acylamino)alkylphosphinic acids 4 (R³ = H or Ph) using penicillin G acylase (PGA) immobilized on three types of mesoporous silicas in both a batch slurry system and in a continuous-flow reactor was studied. The initial hydrolytic deacylation rates in the presence of those catalysts were measured and the relationships between the substrate structure and the enzyme efficiency are discussed. The stereospecific hydrolysis of the N-acyl group of both racemic N-acylated phosphorus analogues of amino acids and their esters catalyzed by the immobilized PGA proved to be a highly effective method for the kinetic resolution of all the investigated compounds, with the stereochemical preference of PGA for (R)-substrates.     

Visconata: A rare flavonol having long chain fatty acid from Dodonaea viscosa which inhibits Human neutrophil elastase (HNE)

A series of flavonoids were isolated from Dodonaea Viscosa and tested for inhibition of human neutrophil elastase (HNE), enzyme involved in inflammatory disorders. Isolated compounds were identified as a novel flavonol (1) along with eight known flavonoids (2–9). Novel flavonol, visconata (1) has a very rare skeleton having odd numbered long chain (C19) fatty acid, which was completely identified by mass fragmentation and 2D NMR analysis. All compounds (1–9) inhibited HNE in dose dependent manner with IC₅₀s ranging between 2.4 and 150 μM. Visconata (1) emerged to be the most potent compound with 2.4 μM of IC₅₀. In kinetic studies, compound (1) was observed to be reversible, noncompetitive inhibitor having K_i = 1.8 μM, whereas other flavonoids (2–9) displayed mixed type inhibition.     

Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design,synthesis and biological evaluation

A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain.     

Dialkyl- and diaryl-platinum(II) complexes with secondary phosphines: Preparation,structure and thermal reaction giving the metallopolymer

Alkyl and arylplatinum complexes with 1,5-cyclooctadiene ligand, [PtR₂(cod)] (R = Me, Ph, C₆H₄-p-CF₃, C₆F₅), react with secondary phosphines, PHR′₂ (R′ = i-Bu, t-Bu, Ph), to afford the mononuclear platinum complexes, cis-[PtR₂(PHR′₂)₂] (1a: R = Me, R′ = i-Bu; 1b: R = Me, R′ = t-Bu; 1c: R = Me, R′ = Ph; 2a: R = Ph, R′ = i-Bu; 2b: R = Ph, R′ = t-Bu; 2c: R = R′ = Ph; 3a: R = C₆H₄-p-CF₃, R′ = i-Bu; 3b: R = C₆H₄-p-CF₃, R′ = t-Bu; 3c: R = C₆H₄-p-CF₃, R′ = Ph; 4a: R = C₆F₅, R′ = i-Bu; 4c: R = C₆F₅, R′ = Ph) in 81–98% yields. Molecular structures of the complexes except for 1a, 1c and 2a were determined by X-ray crystallography. Complex 1b has a square-planar structure with Pt–C(methyl) bonds of 2.083(8) and 2.109(8) Å, while the Pt–C(aryl) bonds of 2b–c, 3a–c, 4a and 4c (2.055(1)–2.073(8) Å) are shorter than them. Thermal decomposition of 1b, 2a–c, and 3a–c releases methane, biphenyl or 4,4′-bis(trifluoromethyl)biphenyl as the organic products, which are characterized by NMR spectroscopy. The solid product of the thermal reactions of 2b and 2c were characterized as the metallopolymers formulated as [Pt(PR′₂)₂]_n (5b: R′ = ^tBu; 5c: R′ = Ph), based on the solid-state NMR and elemental analyses.     

Synthesis and characterization of thiosemicarbazone derivatives of 2-chloro-4-hydroxy-benzaldehyde and their rhenium(I) complexes

N-Thioamide thiosemicarbazone derived of 2-chloro-4-hydroxy-benzaldehyde (R = H, HL¹; R = Me, HL² and R = Ph, HL³) have been prepared and their reaction with fac-[ReX(CO)₃(CH₃CN)₂] (X = Br, Cl) in chloroform gave the adducts [ReX(CO)₃(HL)] (1a X = Cl, R = H; 1a′ X = Br, R = H; 1b X = Cl, R = CH₃; 1b′ X = Br, R = CH₃; 1c X = Cl, R = Ph; 1c′ X = Br, R = Ph) in good yield. Complexes 1a′ and 1b’ were also obtained by the reaction of HL¹ and HL³ with [ReBr(CO)₅] in toluene.All the compounds have been characterized by elemental analysis, mass spectrometry (FAB), IR and ¹H NMR spectroscopic methods. Moreover, the structures of HL², HL³ and 1a·H₂O were also established by X-ray diffraction. In 1a, the rhenium atom is coordinated by the sulphur and the azomethine nitrogen atoms, forming a five-membered chelate ring, as well as three carbonyl carbon and chloride atoms. The resulting coordination polyhedron can be described as a distorted octahedron.The study of the crystals obtained by slow evaporation of methanol and DMSO solutions of the adducts 1a′ and 1b, respectively, showed the formation of dimer structures based on rhenium(I) thiosemicarbazonates [Re₂(L¹)₂(CO)₆]·3H₂O (2a)·3H₂O and [Re₂(L²)₂(CO)₆]·(CH₃)₂SO (2b)·2(CH₃)₂SO. Amounts of these thiosemicarbazonate complexes [Re₂(L)₂(CO)₆] (2) were obtained by reaction of the corresponding free ligands with [ReCl(CO)₅] in dry toluene.In 2a·3H₂O and 2b·2(CH₃)₂SO the dimer structures are established by Re–S–Re bridges, where S is the thiolate sulphur from a N,S-bidentate thiosemicarbazonate ligand. In both structures the rhenium coordination sphere is similar; the dimers are in the same diamond Re₂S₂ face.     

Highly sensitive fluorescent sensor targeting CuCl2 based on thiophene attached anthracene compound (TA)

A novel thiophene attached anthracene (TA) based fluorescent compound was designed and synthesized. The TA showed a high quantum yield (Qy = 0.34) in regard to fluorescence. We applied this TA compound to detect specific metal compound and found that it could identify CuCl₂ from other metals through dramatic fluorescence change at λ_max = 460 nm. It showed strong quenching fluorescence property with CuCl₂ while with other metal compounds it exhibited strong blue fluorescence emission. UV/Vis absorption spectroscopy clearly demonstrated that the quenching property of TA at λ_max = 460 nm was due to overlapping of the fluorescence peak of TA at λ_max = 460 nm and the absorption band of CuCl₂ (from 190 nm to 525 nm). Binding constant (K′), which was 0.0895 mM^?2, indicated a complexation ratio between TA and CuCl₂ as 1:2 and this interaction induced quenching property.     

Synthesis,structure and fluorescence of a novel three-dimensional inorganic–organic hybrid polymer constructed from trimetallic clusters and mixed carboxylate ligands

A new inorganic–organic hybrid framework coordination polymer, Cd₃(BDC)_0.5(BTC)₂(DMF)(H₂O)·3DMF·H₃O·H₂O 1, in which two carboxylate ligands, 1,4-benzenedicarboxylic acid (H₂BDC) and 1,3,5-benzenetricarboxylic acid (H₃BTC), coordinate with cadmium ions, has been synthesized under mild conditions and its structure solved by single-crystal X-ray diffraction (XRD) analysis. Polymer 1 crystallizes in the monoclinic system, space group P2₁/c (No. 14) with a=15.750(3) Å, b=14.501(3) Å, c=19.363(4) Å, β=113.67(3)°, V=4050.4(14) Å³, Z=4, R1=0.0374 and wR2=0.1148. Its structure revealed that the nine vertices of the secondary building units are linked by benzene rings from both H₃BTC and H₂BDC ligands to form a 3D network with 10×10 Å channels along [001] direction. Complex 1 is characterized by inductively coupled plasma analysis, powder XRD, infrared spectroscopy and thermogravimetric analysis. Polymer 1 exhibits intense fluorescence at 358 and 377 nm with λ_excitation=208 nm in the solid state at room temperature.     

Efficient,collective synthesis and nitric oxide inhibitory activity of rubrolides E,F, R,S and their derivatives

An efficient first synthesis of biologically significant natural butenolides, rubrolides F (1f), R (1r), S (1s) & its 7″,8″-didehydro derivative (1sa), and 3″-bromo rubrolide (1fa) along with the synthesis of rubrolide E (1e) and its di-O-methyl derivative (1ea) is accomplished in a collective fashion from commercially available and inexpensive precursors in overall yields of 14–48.5%. Key features are Wittig-Horner reaction, SeO₂-induced tandem allylic hydroxylation/intramolecular cyclization and Knoevenagel condensation. Next, in their inhibitory activity towards nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages as an indicator of anti-inflammatory activity, all compounds displayed good inhibitory activity in a concentration-dependent manner. None of the compound exhibited notable cytotoxicity at the highest concentration (10 μM) and IC₅₀ values are found in the range from 8.53 to 17.85 μM.     

Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors

The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-β-lactamase inhibitors is described. The reaction of β-aminoalcohols and 2,5-dihydroxy-1,4-dithiane led to oxazolidinylthiazolidines and/or dithioazabicycles as the main products. The distribution pattern depends mainly on the aminoalcohol substituents. In a one-pot reaction, four new bonds are formed in good yields and with high atom efficiency. When the oxazolidinylthiazolidines are formed, two stereogenic centres are generated with high enantiospecificity. The reaction mechanism is discussed based on crystallographic data and interconversion studies. Two oxazolidinylthiazolidines were evaluated as inhibitors of the potent lactamase NDM-1 and compound 4f displayed competitive inhibition with K_i = 1.6 ± 0.6 μM.     

Trichothiazole A,a dichlorinated polyketide containing an embedded thiazole isolated from Trichodesmium blooms

Mass spectrometry-guided isolation of the lipophilic extract of Trichodesmium bloom material led to the isolation and structure characterization of a new thiazole-containing di-chlorinated polyketide (1). The structure of 1 was deduced using 1D and 2D NMR analysis, high-resolution mass spectrometry analysis and complementary spectroscopic procedures. Trichothiazole A possesses interesting structural features, such as a terminal alkyne, two vinyl chlorides and a 2,4-disubstituted thiazole. Trichothiazole A showed moderate cytotoxicity to Neuro-2 A cells (EC₅₀: 13.3 ± 1.1 μM).     

A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane

A novel C₃-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity.     

New metastable hybrid phase,Zn2(OH)2(C8H4O4), exhibiting unique oxo-penta-coordinated Zn(II) atoms

The metastable phase (phase 1) Zn(OH)₂(tp)₂ (tp = C₈H₄O₄^2?) was found to be an intermediate forming during the hydrothermal synthesis of Zn₃(OH)₄tp (phase 2). Its structure has been determined ab initio from synchrotron powder diffraction data and refined with the Rietveld method: space group P2₁/c, a = 3.48856(2) Å, b = 5.84645(2) Å, c = 22.1331(1) Å, β = 103.46(1)°, D_x = 2.488 g/cm³, R_p = 0.10, R_B = 0.095 (402 independent reflections). The structures of the two analogues were compared. Whereas a mixed coordination of the zinc atoms was found in phase 2, phase 1 exhibits only penta-coordinated Zn(II). Moreover, different optical properties were observed, Zn₂(OH)₂(tp) showing photoluminescence at 378 nm under λ_ex = 316 nm.