New Chiral and Achiral Imines and Bisimines Derived from 2‐Phenyl‐1H‐imidazole‐4‐carbaldehyde. Synthesis,Structural Studies and Complexation Stability Constants

Synthesis and properties of new imines and bisimines derived from 2‐phenyl‐1H‐imidazole‐4‐carbaldehyde and amines/diamines were studied. (2‐Phenyl‐1H‐imidazole‐4‐yl)methanol was oxidized to 2‐phenyl‐1H‐imidazole‐4‐carbaldehyde with better yield 55% by the modification of literature procedure. This aldehyde was condensed with the following achiral and chiral amines or 1,2‐diamines: ethanamine, propan‐1‐amine, butan‐1‐amine, 2‐methylpropan‐1‐amine, cyclohexanamine, (2R)‐ and (2S)‐3‐methylbutan‐2‐amine, (1R)‐ and (1S)‐1‐cyclohexylethanamine, (S)‐1‐aminopropan‐2‐ol, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)ethanamine, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)‐2‐methylpropan‐1‐amine, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)‐3‐methylbutan‐1‐amine, ethane‐1,2‐diamine, and (1R,2R)‐ and (1S,2S)‐cyclohexane‐1,2‐diamine. Sixteen condensation products, especially chiral imines and bisimines, were prepared by founded procedures in 45–99% of yields and characterized by the ¹H NMR spectroscopy in solution, mass spectrometry, and elemental analyses. The optical rotation values in the case of chiral ones were also observed. Stability constants of Cu(II) complexes of selected prepared imines/bisimines were determined.     

Novel and Stereospecific Synthesis of (2S)‐3‐(2,4,5‐Trifluorophenyl)propane‐1,2‐diol from D‐Mannitol

A stereospecific synthesis of (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol from D ‐mannitol has been developed. The reaction of 2,3‐O‐isopropylidene‐D ‐glyceraldehyde with 2,4,5‐trifluorophenylmagnesium bromide gave [(4R)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl](2,4,5‐trifluorophenyl)methanol in 65% yield as a mixture of diastereoisomers (1 : 1). The Ph₃P catalyzed reaction of the latter with C₂Cl₆ followed by reduction with Pd/C‐catalyzed hydrogenation gave (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol with >99% ee and 65% yield.     

A semi‐synthetic analog of the cembranoid sarcophine

The title mol­ecule, 2(R)‐[(1E,3E,7S,8S,11E,13R)‐13‐hydroxy‐4,8,12‐tri­methyl‐7,8‐epoxy­cyclo­tetradeca‐1,3,11‐trien‐1‐yl]­propane‐1,2‐diol, C₂₀H₃₂O₄, is a semi‐synthetic analog of sarcophine, the natural cembranoid of marine origin, isolated from the soft coral Sarcophyton glaucum. The conformation of the 14‐membered ring differs substantially from that of sarcophine. The two OH groups of the propane‐1,2‐diol moiety form an unusual weak intramolecular hydrogen bond with an O⋯O distance of 2.788 (2) Å, and the mol­ecules are linked into double chains by intermolecular hydrogen bonds with O⋯O distances of 2.772 (2) and 2.849 (2) Å.     

New Nonhydrolyzable Mimetics of Sialyl Lewis X and Their Binding Affinity to P‐Selectin

Wittig olefination of (2S,3R,5S,6R)‐5‐(acetyloxy)‐tetrahydro‐6‐[(methoxymethoxy)methyl]‐3‐(phenylthio)‐ 2H‐pyran‐2‐acetaldehyde ((+)‐ 10 ) with {2‐[(2S,3R,4R,5R,6S)‐tetrahydro‐3,4,5‐tris(methoxymethoxy)‐6‐methyl‐ 2H‐pyran‐2‐yl]ethyl}triphenylphosphonium iodide ((?)‐ 11 ) gave a (Z)‐alkene derivative (+)‐ 12 that was converted into (αR,2R,3S,4R,5R,6S)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐5‐(phenylthio)‐6‐{(2Z)‐4‐[(2S,3S,4R,5S,6S)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2H‐pyran‐2‐yl]but‐2‐enyl}2H‐pyran‐4‐acetic acid ( 8 ), (αR,2R,3S,4R,6S)‐tetrahydro‐α,3‐dihydroxy‐2‐(hydroxymethyl)‐6‐{4‐[(2S,3S,4R,5S,6S)‐tetrahydro‐3,4,5‐trihydroxy‐6‐methyl‐2H‐pyran‐2‐yl]butyl}‐2H‐pyran‐4‐acetic acid ( 9 ), and simpler analogues without the hydroxyacetic side chain such as (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{(2Z)‐4‐[(2S,3R,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐3‐(phenylthio)‐2H‐pyran‐2‐yl]but‐2‐enyl}‐2H‐pyran‐3,4,5‐triol ( 30 ), (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{[(2S,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐2‐yl]butyl}‐2H‐pyran‐3,4,5‐ triol ((?)‐ 41 ) and (2S,3S,4R,5S,6S)‐tetrahydro‐6‐methyl‐2‐{(2Z/E))‐4‐[(2R,5S,6R)‐tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐2‐yl]but‐2‐enyl}‐2H‐pyran‐3,4,5‐triol ( 43 ). The key intermediates (+)‐ 10 and (?)‐ 11 were derived from isolevoglucosenone and from L ‐fucose, respectively. The following IC₅₀ values were measured in a ELISA test for the affinities of sialyl Lewis x tetrasaccharide, 8, 9, 30 , (?)‐ 41 , and 43 toward P‐selectin: 0.7, 2.5–2.8, 7.3–8.0, 5.3–5.9, 5.0–5.2, and 3.4–4.1 mM , respectively.     

Synthesis of New Carnosine Derivatives of β‐Cyclodextrin and Their Hydroxyl Radical Scavenger Ability

Several in vitro and in vivo studies have suggested that carnosine can act as a scavenger of reactive oxygen species and intracellular proton buffer. On the other hand, carnosinase is a specific peptidase able to destroy the biological active dipeptide. To overcome this constraint, β‐cyclodextrin (β‐CD) was functionalized with carnosine to give the following new compounds: 6^A‐[(3‐{[(1S)‐1‐carboxy‐2‐(1H‐imidazol‐4‐yl)ethyl]amino}‐3‐oxopropyl)amino]‐6^A‐deoxy‐β‐cyclodextrin ( 1 ), 6^A‐[(β‐alanyl‐L ‐histidyl)amino]‐β‐cyclodextrin ( 2 ), and (2^AS,3^AR)‐3^A‐[(3‐{[(1S)‐1‐carboxy‐2‐(1H‐imidazol‐4‐yl)ethyl]amino}‐3‐oxopropyl)amino]‐3^A‐deoxy‐β‐cyclodextrin ( 3 ). Pulse‐radiolysis investigation showed that the β‐CD derivatives 1 – 3 are excellent scavengers of OH^. radicals. Their activity is not only due to the formation of the stable imidazole‐centered radical, but also to the scavenger ability of the glucose moieties of the macrocycle (Scheme). This effect is independent of the disposition of the imidazole ring. In fact, the quenching constant values are similar for the three compounds.     

Structural studies and antileishmanial activity of 2‐acetylpyridine and 2‐benzoylpyridine nitroimidazole‐derived hydrazones

Three imidazole hydrazone compounds, namely 2‐(4‐nitro‐1H‐imidazol‐1‐yl)‐N′‐[1‐(pyridin‐2‐yl)ethylidene]acetohydrazide, C₁₂H₁₂N₆O₃, ( 1 ), 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N′‐[1‐(pyridin‐2‐yl)ethylidene]acetohydrazide, C₁₂H₁₂N₆O₃, ( 2 ), and 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N′‐[(phenyl)(pyridin‐2‐yl)methylidene]acetohydrazide, C₁₇H₁₄N₆O₃, ( 3 ), were obtained and fully characterized, including their crystal structure determinations. While all the compounds proved not to be cytotoxic to J774.A1 macrophage cells, ( 1 ) and ( 3 ) exhibited activity against Leishmania chagasi, whereas ( 2 ) was revealed to be inactive. Since both ( 1 ) and ( 3 ) exhibited antileishmanial effects, while ( 2 ) was devoid of activity, the presence of the acetyl or benzoyl groups was possibly not a determining factor in the observed antiprotozoal activity. In contrast, since ( 1 ) and ( 3 ) are 4‐nitroimidazole derivatives and ( 2 ) is a 2‐nitroimidazole‐derived compound, the presence of the 4‐nitro group probably favours antileishmanial activity over the 2‐nitro group. The results suggested that further investigations on compounds ( 1 ) and ( 3 ) as bioreducible antileishmanial prodrug candidates are called for.     

Azole. 45.

The three title compounds, namely (Z)‐1‐(4,5‐di­nitro­imidazol‐1‐yl)‐3‐morpholinopropan‐2‐one 2,4‐di­nitro­phenyl­hydrazone, C₁₆H₁₇N₉O₉, (IV), (Z)‐3‐morpholino‐1‐(4‐morpholino‐5‐nitro­imidazol‐1‐yl)propan‐2‐one 2,4‐di­nitro­phenyl­hydrazone, C₂₀H₂₅N₉O₈, (Va), and (E)‐3‐morpholino‐1‐(4‐morpholino‐5‐nitro­imidazol‐1‐yl)propan‐2‐one 2,4‐di­nitro­phenylhydra­zone tetra­hydro­furan solvate, C₂₀H₂₅N₉O₈·C₄H₈O, (Vb), have been prepared and their structures determined. In (IV), the C‐4 nitro group is nearly perpendicular to the imidazole ring and the C‐4—NO₂ bond length is comparable to the value for a normal single Csp²—NO₂ bond. In (IV), (Va) and (Vb), the C‐­5 nitro group deviates insignificantly from the imidazole plane and the C‐5—NO₂ bond length is far shorter in all three compounds than C‐4—NO₂ in (IV). In consequence, the C‐4 nitro group in (IV) is easily replaced by morpholine, while the C‐5 nitro group in (IV), (Va) and (Vb) shows an extraordinary stability on treatment with the amine. The E configuration in (Vb) is stabilized by a three‐centre hydrogen bond.     

Temperature‐induced solid‐to‐solid transformation in helical homochiral coordination polymers

The reactions of (R)‐ and (S)‐4‐(1‐carboxyethoxy)benzoic acid (H₂CBA) with 1,3‐bis(2‐methyl‐1H‐imidazol‐1‐yl)benzene (1,3‐BMIB) ligands afforded a pair of homochiral coordination polymers (CPs), namely, poly[[[μ‐1,3‐bis(2‐methyl‐1H‐imidazol‐1‐yl)benzene][μ‐(S)‐4‐(1‐carboxylatoethoxy)benzoato]zinc(II)] monohydrate], {[Zn(C₁₀H₈O₅)(C₁₄H₁₄N₄)]·H₂O}_n or {[Zn{(S)‐CBA}(1,3‐BMIB)]·H₂O}_n ( 1‐L ), and poly[[[μ‐1,3‐bis(2‐methyl‐1H‐imidazol‐1‐yl)benzene][μ‐(R)‐4‐(1‐carboxylatoethoxy)benzoato]zinc(II)] monohydrate] ( 1‐D ). Three kinds of helical chains exist in compounds 1‐D and 1‐L , which are constructed from Zn^II atoms, 1,3‐BMIB ligands and/or CBA^2? ligands. When the as‐synthesized crystals of 1‐L and 1‐D were further heated in the mother liquor or air, poly[[μ‐1,3‐bis(2‐methyl‐1H‐imidazol‐1‐yl)benzene][μ‐(S)‐4‐(1‐carboxylatoethoxy)benzoato]zinc(II)], [Zn(C₁₀H₈O₅)(C₁₄H₁₄N₄)]_n or [Zn{(S)‐CBA}(1,3‐BMIB)]_n ( 2‐L ), and poly[[μ‐1,3‐bis(2‐methyl‐1H‐imidazol‐1‐yl)benzene][μ‐(R)‐4‐(1‐carboxylatoethoxy)benzoato]zinc(II)] ( 2‐D ) were obtained, respectively. The single‐crystal structure analysis revealed that 2‐L and 2‐D only contained one type of helical chain formed by Zn^II atoms and 1,3‐BMIB and CBA^2? ligands, which indicated that the helical chains were reconstructed though solid‐to‐solid transformation. This result not only means the realization of helical transformation, but also gives a feasible strategy to build homochiral CPs.     

Non‐iterative Asymmetric Synthesis of C15 Polyketide Spiroketals

The 2,2′‐methylenebis[furan] ( 1 ) was converted to 1‐{(4R,6S))‐6‐[(2R)‐2,4‐dihydroxybutyl]‐2,2‐dimethyl‐1,3‐dioxan‐4‐yl}‐3‐[(2R,4R)‐tetrahydro‐4,6‐dihydroxy‐2H‐pyran‐2‐yl)propan‐2‐one ((+)‐ 18 ) and its (4S)‐epimer (?)‐ 19 with high stereo‐ and enantioselectivity (Schemes 1–3). Under acidic methanolysis, (+)‐ 18 yielded a single spiroketal, (3R)‐4‐{(1R,3S,4′R,5R,6′S,7R)‐3′,4′,5′,6′‐tetrahydro‐4′‐hydroxy‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2H]pyran]‐6′‐yl}butane‐1,3‐diol ((?)‐ 20 ), in which both O‐atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (?)‐ 20 (methyl pyranoside formation). Compound (?)‐ 19 was converted similarly into the (4′S)‐epimeric tricyclic spiroketal (?)‐ 21 that also adopts a similar (3S)‐configuration and conformation. Spiroketals (?)‐ 20 , (?)‐ 21 and analog (?)‐ 23 , i.e., (1R,3S,4′R,5R,6′R)‐3′,4′,5′,6′‐tetrahydro‐6′‐[(2S)‐2‐hydroxybut‐3‐enyl]‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2H]pyran]‐4′‐ol, derived from (?)‐ 20 , were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)‐ 21 showed evidence of cancer‐cell‐growth inhibition (P388, ED₅₀: 6.9 μg/ml).     

Neoclerodane Diterpenes from Amoora stellato‐squamosa

From the twigs of Amoora stellato‐squamosa, five new neoclerodane diterpenes have been isolated and characterized, methyl (13E)‐2‐oxoneocleroda‐3,13‐dien‐15‐oate (=methyl (2E)‐3‐methyl‐5‐[(1S,2R,4aR,8aR)‐1,2,3,4,4a,7,8,8a‐octahydro‐1,2,4a,5‐tetramethyl‐7‐oxo‐naphthalen‐1‐yl]pent‐2‐enoate; 1 ), (13E)‐2‐oxoneocleroda‐3,13‐dien‐15‐ol (=(4aR,7R,8S,8aR)‐1,2,4a,5,6,7,8,8a‐octahydro‐8‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐4,4a,7,8‐tetramethylnaphthalen‐2(1H)‐one; 2 ), (3α,4β,13E)‐neoclerod‐13‐ene‐3,4,15‐triol (=(1R,2R,4aR, 5S,6R,8aR)‐decahydro‐5‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalene‐1,2‐diol; 3 ), (3α,4β,13E)‐4‐ethoxyneoclerod‐13‐ene‐3,15‐diol (=(1R,2R,4aR,5S,6R,8aR)‐1‐ethoxydecahydro‐5‐[(E)‐5‐hydroxy‐3‐methylpent‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalen‐2‐ol; 4 ), and (3α,4β,14RS)‐neoclerod‐13(16)‐ ene‐3,4,14,15‐tetrol (=(1R,2R,4aR,5S,6R,8aR)‐decahydro‐5‐[3‐(1,2‐dihydroxyethyl)but‐3‐enyl]‐1,5,6,8a‐tetramethylnaphthalene‐1,2‐diol; 5 ), together with two known compounds, (13E)‐neocleroda‐3,13‐diene‐15,18‐diol ( 6 ) and (13S)‐2‐oxoneocleroda‐3,14‐dien‐13‐ol ( 7 ).     

Synthesis and Absolute Configuration at C(8) of ‘p‐Menthane‐3,8,9‐triol’ Derived from (–)‐Isopulegol

Two diastereoisomers of the new, potentially insecticidal ‘p‐menthane‐3,8,9‐triol’ (=(2S)‐ and (2R)‐ 2‐[(1R,2R,4R)‐2‐hydroxy‐4‐methylcyclohexyl]propane‐1,2‐diol; (8S)‐ and (8R)‐ 1 ), have been synthesized from (–)‐isopulegol by both conventional dihydroxylation and catalytic Sharpless dihydroxylation (Scheme). The absolute configuration at C(8) of the corresponding orthoformate adduct (8S)‐ 3a was determined by ¹H‐NMR and X‐ray crystallographic analysis (Figure).     

Silica‐tethered cuprous acetophenone thiosemicarbazone (STCATSC) as a novel hybrid nano‐catalyst for highly efficient synthesis of new 1,2,3‐triazolyl‐based metronidazole hybrid analogues having potent antigiardial activity

The preparation, characterization and application of silica‐tethered cuprous acetophenone thiosemicarbazone (STCATSC) as a novel hybrid nano catalyst for synthesis of new 1,2,3‐triazolyl‐based metronidazole hybrid analogues is described. STCATSC is fully characterized by different microscopic, spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission, X‐ray diffraction (XRD), Energy‐dispersive X‐ray spectroscopy (EDS), thermogravimetric analysis (TGA), FT‐IR and inductively coupled plasma (ICP) analysis. This catalyst is used to prepare the new 1,2,3‐triazolyl‐based metronidazole hybrid analogues. The ‘Click’ Huisgen cycloaddition reaction of 2‐methyl‐5‐nitro‐1‐prop‐2‐ynyl‐1H‐imidazole with diverse β‐azidoalcohols in a THF‐water media at R.T. provides the products in good to excellent yields using STCATSC. STCATSC is proved to be a stable, low cost, reusable and environmentally benign hybrid catalyst. Products are in vitro tested against Giardia lamblia (G. lamblia) in which determined that all compounds exhibit varied promising antigiardial activity compare to metronidazole as a reference drug. Among the products, 1‐(4‐((2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐3‐phenethoxypropan‐2‐ol and 1‐(4‐((2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐3‐(3‐phenylpropoxy)propan‐2‐ol are demonstrated to exhibit the potent antigiardial activity even stronger than metronidazole.     

Synthesis and Structure of an Enantiomerically Pure C2 Symmetric Ferrocenyl Carbene

The straightforward, high‐yield synthesis and X‐ray structural analysis of the air‐stable planar‐chiral bis(ferrocenyl)carbene 1,3‐bis‐{(1R)‐1‐[(1R)‐1‐(trimethylsilyl)ferrocen‐2‐yl]ethyl}imidazol‐2‐ylidene ( 5 ) is reported. Compound 5 is obtained in four steps from the amine [(1R)‐1‐(dimethylamino)ethyl]ferrocene ( 1 ) upon diastereoselective silylation, methylation, nucleophilic substitution by imidazole, and deprotonation. The X‐ray crystal structure of the free carbene shows the typical conformational features of the 1,2‐disubstituted ferrocenyl units, as found in other ferrocenyl ligands derived from 1 .     

Asymmetric Reaction of Simple Nitro Compounds with Chiral 1,3‐Oxazolidin‐2‐ones

The chiral oxazolidinone 1 (=[(3aS,6R,7aR)‐tetrahydro‐8,8‐dimethyl‐2‐oxo‐4H‐3a,6‐methano‐1,3‐benzoxazol‐3‐yl](oxo)acetaldehyde) was found to react stereoselectively with simple nitro compounds in the presence of Al₂O₃ or Bu₄NF?3 H₂O (TBAF) as catalysts, affording the diastereoisomeric nitro alcohols 3 – 6 with good asymmetric induction. When Al₂O₃ was used, the (S)‐configuration at the center bearing the OH group was generated, with the relative syn‐configuration for the major diastereoisomers. In the case of the nitro‐aldol reaction catalyzed by TBAF, an opposite asymmetric induction was found for two nitro compounds. In contrast to 1 , compound 12 (=((4R,5S)‐4‐methyl‐2‐oxo‐5‐phenyl‐1,3‐oxazolidin‐3‐yl)(oxo)acetaldehyde), a derivative of Evans auxiliary, gave rise to poor asymmetric induction in Henry reactions.     

Azole. 44.

The structure analyses of racemic 3‐chloro‐1‐(4‐morpholino‐5‐nitro­imidazol‐1‐yl)­propan‐2‐ol, C₁₀H₁₅ClN₄O₄, (II), and 3‐chloro‐1‐(5‐morpholino‐4‐nitro­imidazol‐1‐yl)­propan‐2‐ol, C₁₀H₁₅ClN₄O₄, (III), have been undertaken in order to determine the position of the morpholine residue in these two isomers. The morpholine residue in (II) is connected at the 4‐position, while in (III), it is connected at the 5‐position of the imidazole ring. The morpholine mean planes and nitro groups in the two compounds deviate from the imidazole planes to different extents. The nitro groups in (II) and (III) take part in the conjugation system of the imidazole rings. In consequence, the exocyclic C—N bonds are significantly shorter than the normal single Csp²—NO₂ bond and the nitro groups in (II) and (III) show an extraordinary stability on treatment with morpholine and piperidine [Gzella, Wrzeciono & Pöppel (1999). Acta Cryst. C 55 , 1562–1565]. In the crystal lattice, the mol­ecules of both compounds are linked by O—H?N and C—H?O intermolecular hydrogen bonds.     

Fate of the Oxygen Atoms in the Diol‐Dehydratase‐Catalyzed Dehydration of meso‐Butane‐2,3‐diol

¹⁸O‐Substituted propane‐1,2‐diols and meso‐butane‐1,2‐diols were synthesized and fed to growing cells of Lactobacillus brevis. Propan‐1‐ol and butan‐2‐ol, prepared from such diols through diol‐dehydratase‐catalyzed dehydration followed by intracellular reduction, were analyzed for their ¹⁸O‐content. For each propane‐1,2‐diol enantiomer, partial retention or complete loss of the isotope appeared to be related to the mode of substrate binding. Specific retention of the O‐atom linked to the (R)‐configured C‐atom of meso‐butane‐1,2‐diol indicates that the diol dehydratase handles this substrate like (R)‐propane‐1,2‐diol.     

Carbocyclic 5′‐norcytidine (5′‐norcarbodine)

A preparation of (1′R,2′S,3′R,4′S)‐1‐(2′,3′,4′‐trihydroxycyclopent‐1′‐yl)‐lH‐cytosine (5′‐norcarbodine, 3 ) has formally been achieved in 2 steps from (+)‐(1R,4S)‐4‐hydroxy‐2‐cyclopenten‐1‐yl acetate ( 4 ) and cytosine. The L‐like enantiomer of 3 (that is, 6 ) is also reported using the enantiomer of 4 (that is, 7 ). In evalu ating 3 and 6 for antiviral potential against a number of viruses, compound 3 was found to have activity towards Epstein‐Barr virus (EBV).     

Enantioselective Synthesis of the Natural Product (S)‐Rugulactone

A simple and efficient enantioselective synthesis of (6S)‐5,6‐dihydro‐6‐[(2E)‐4‐oxo‐6‐phenylhex‐2‐en‐1‐yl]‐2H‐pyran‐2‐one (=(S)‐rugulactone) has been accomplished. The synthesis started from commercially available propane‐1,3‐diol and ethyl 3‐phenylpropanoate and involve the Horner? Wadsworth? Emmons (HWE) and Still's modified HWE olefinations, and Sharpless asymmetric epoxidation.     

Chemical Constituents from the Fermented Mycelia of the Medicinal Fungus Xylaria nigripes

Nineteen compounds mainly including pyrrole‐containing alkaloids and phytosterols were isolated from the EtOH extract of the fermented mycelia of Xylaria nigripes, a precious medicinal fungus known as Wuling Shen in Chinese. On the basis of spectroscopic methods, the structures of the new naturally occurring compounds were determined to be (4S)‐3,4‐dihydro‐4‐(4‐hydroxybenzyl)‐3‐oxo‐1H‐pyrrolo[2,1‐c][1,4]oxazine‐6‐carbaldehyde ( 1 ), methyl (2S)‐2‐[2‐formyl‐5‐(hydroxymethyl)‐1H‐pyrrol‐1‐yl]‐3‐(4‐hydroxyphenyl)propanoate ( 2 ), and 3‐{4‐[(2R)‐(2,3‐dihydroxy‐3‐methylbutoxy]phenyl}‐7‐hydroxy‐4H‐chromen‐4‐one ( 3 ), respectively. The absolute configurations of 1 and 2 were deduced by the observed Cotton effects in their circular dichroism (CD) spectra, whereas that of the 1,2‐diol moiety in 3 was determined using the Snatzke's method. Their biological activities such as neuroprotective, anti‐neuroinflammatory, and cytotoxic properties were also reported.     

Synthesis,Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Nonsymmetrically 4‐(Methoxycarbonyl)benzyl‐Substituted N‐Heterocyclic Carbene–Silver Acetate Complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ), 1H‐benzimidazole ( 1c ), 1‐methyl‐1H‐imidazole ( 1d ), and 1‐methyl‐1H‐benzimidazole ( 1f ) with methyl 4‐(bromomethyl)benzoate ( 2 ), symmetrically and nonsymmetrically 4‐(methoxycarbonyl)benzyl‐substituted N‐heterocyclic carbene (NHC) precursors, 3a – 3f , were synthesized. These NHC precursors were then reacted with silver(I) acetate (AgOAc) to yield the NHC–silver acetate complexes (acetato‐κO){1,3‐bis[4‐(methoxycarbonyl)benzyl]imidazol‐2‐ylidene}silver ( 4a ), (acetato‐κO){4,5‐dichloro‐1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4b ), (acetato‐κO){1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl}silver ( 4c ), (acetato‐κO){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4d ), (acetato‐κO){4,5‐dichloro‐1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4e ), and (acetato‐κO){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl}silver ( 4f ), respectively. The three NHC–AgOAc complexes 4a, 4c , and 4d were characterized by single‐crystal X‐ray diffraction. All compounds studied in this work were preliminarily screened for their antimicrobial activities in vitro against Gram‐positive bacteria Staphylococcus aureus, and Gram‐negative bacteria Escherichia coli using the qualitative disk‐diffusion method. All NHC–AgOAc complexes exhibited weak‐to‐medium antibacterial activity with areas of clearance ranging from 4 to 7 mm at the highest amount used, while the NHC precursors showed significantly lower activity. In addition, NHC–AgOAc complexes 4a and 4b , and 4d – 4f exhibited in preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 medium‐to‐high cytotoxicities with IC₅₀ values ranging from 3.3±0.4 to 68.3±1 μM .