Stereochemical assignments of rubiaquinones A–C,naphthoquinone derivatives from Rubia yunnanensis

Three new naphthoquinone derivatives, rubiaquinones A–C (1–3), were isolated from the roots of Rubia yunnanensis. Rubiaquinone A (1) was a racemic naphthoquinone dimer consisting of a 1,4-dihydroxynaphthalene and a 4-hydroxy-1,2-naphthoquinone moieties with a 2-oxo-propyl group. Rubiaquinones B (2) and C (3) were structurally unique trimeric naphthoquinones with a racemic nature possessing one chiral axis and one chiral carbon in common. The planar structures of 1–3 were assigned by detailed spectroscopic analyses, and enantiomers of 1–3 were obtained by optical resolutions. The absolute configurations of (+)-1 and (?)-1 were elucidated by interpretation of the ECD spectra with the aid of TDDFT ECD calculation, while those of enantiomers obtained from 2 and 3 were assigned by analyses of the composite ECD spectra generated by summing appropriate ECD spectra of enantiomers. Rubiaquinone A (1) exhibited antimicrobial activity against Bacillus subtilis.     

Two pairs of new alkaloid enantiomers with a spiro [benzofuranone-benzazepine] skeleton from the bark of Juglans mandshurica

(±)-Juglanaloid A (1) and B (2), two pairs of novel naturally occurring alkaloid enantiomers bearing an unprecedented spiro [benzofuranone-benzazepine] skeleton, were isolated from the bark of Juglans mandshurica Maxim. The unusual 6, 5, 7, 6-cyclic system with a rare spiro cyclic center at C-4 was determined on the basis of spectroscopic data. Chiral separation of 1 and 2 yielded two pairs of enantiomers, 1a/1b and 2a/2b. The absolute configurations were established by comparing the experimental and calculated electronic circular dichroism spectra. The potential anti-AD properties of 1a/1b and 2a/2b were evaluated by the Thioflavin T assay.     

Synthesis of new chiral keto alcohols by baker’s yeast

Fourteen chiral α- and β-keto alcohols 2a–2r were synthesized by the asymmetric reduction of their corresponding diketones 1a–1r via baker’s yeast. In addition, ten corresponding racemic α-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral α-keto alcohols 2i, 2j and chiral β-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker’s yeast for the first time. There are some studies in the literature where baker’s yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (¹H and ¹³C), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed.     

Enamine chemistry—XXV: Reduction of enaminones by LiAlH4 and NaBH4. Synthesis of α,β-unsaturated aldehydes

Cyclohexanone, 2-methyl-cyclohexanone and 4-methyl-cyclohexanone, 1, were transformed into the enaminones 4a–4e by the following two routes: (A): Acylation of the enamines, 2, derived from 1 and secondary amines (pyrrolidine, morpholine and piperidine) by ethyl chloroformate, and (B): Condensation of 1 with diethyl oxalate, giving the β-ketoesters 3, followed by reaction with the secondary amines. Ethyl 2(-1-pyrrolidinyl)-1-cyclopentene-1-carboxylate, 4f, and methyl 3-(1-pyrrolidinyl)-2-butenoate, 4g, were prepared from ethyl 2-oxo-1-cyclopentanecarboxylate and ethyl 3-oxo-butanoate, respectively, by condensation with pyrrolidine. Reduction of 4a by LAH afforded 1-cyclohexen-1-carboxaldehyde, 5a, 1-cyclohexene-1-methanol, 6a, and 1-(1-cyclohexene-1-methyl)pyrrolidine, 7a, in yields depending on the molar ratio of LAH/4a. Reduction of 4f by LAH gave cyclopentene-1-methanol, 6b, 1-(1-cyclopentene-1-methyl)pyrrolidine, 7b, and ethyl-2(1-pyrrolidinyl)-1-cyclo-pentanecarboxylate, 8b. Compound 4g, when reduced with LAH, yielded methyl 3-(1-pyrrolidinyl) butanoate, 8c (main product) and 1-(2-butenyl)pyrrolidine, 7c (minor). Reduction of 4 by NaBH₄ afforded exclusively the saturated β-aminoesters, 8 in high yields. The reductions with LAH and NaBH₄ are rationalized in terms of the HSAB principle.     

In vitro antioxidant properties of new thiazole derivatives

A series of novel N2-[2-chloro-4(3,4,5-trimethoxy phenyl azetidin-1-yl]-N4-(substituted aryl)-1,3-thiazole-2,4-diamine (4a–g) were synthesized starting from 3,4,5-trimethoxy benzaldehyde thiosemicarbazone (1). The compound (1) was obtained by condensing 3,4,5-trimethoxy benzaldehyde with thiosemicarbazide in methanol. 3,4,5-Trimethoxy benzaldehyde thiosemicarbazone (1) on treatment with chloracetyl chloride afforded 4-chloro-[2-(3,4,5-trimethoxy benzylidine) hydrazinyl]-1,3-thiazole (2). Compound (2) was reacted with chloracetyl chloride and triethylamine to obtain the corresponding 4-chloro-N-[2-chloro-4(3,4,5-trimethoxy phenyl) azetidin-1-yl]-1,3-thiazole-2-amine (3). Various substitutions on compound 3 with secondary amines yielded series of compounds (4a–g). The newly synthesized compounds were characterized by IR, ¹H NMR, elemental analysis and mass spectral studies. All the compounds were screened for their in vitro antioxidant properties. The IC₅₀ values of compounds 3 and 4a–g revealed that some of the synthesized compounds were showing potent antioxidant activity.     

Synthesis, photophysical properties and sugar-dependent in vitro photocytotoxicity of pyrrolidine-fused chlorins bearing S-glycosides

Eight S-glycosylated 5,10,15,20-tetrakis(tetrafluorophenyl)porphyrins (1a′, 1b′, 1a and 1b (a: S-glucosylated, b: S-galactosylated)) and their 1,3-dipolar cycloadducts, i.e. chlorins 2a′, 2b′, 2a and 2b were prepared by nucleophilic substitution of the pentafluorophenyl groups with S-glycoside. These photosensitizers were characterized by ¹H, ¹³C and ¹⁹F NMR spectroscopies and elemental analysis. The photocytotoxicity of the S-glycosylated photosensitizers and the parent porphyrin (1) and chlorin (2) was examined in HeLa cells. Photosensitizers 1, 2, 1a′, 1b′, 2a′ and 2b′ showed no significant photocytotoxicity at the concentration of 0.5 μM, while the deprotected photosensitizers 1a, 1b, 2a and 2b were photocytotoxic. The strong inhibition by sodium azide of the photocytotoxicity of these photosensitizers suggested that ¹O₂ is the main mediator. The S-glucosylated photosensitizers 1a and 2a showed higher photocytotoxicity than S-galactosylated 1b and 2b, respectively. The cellular uptake of 1a and 2a increased up to 24 h, while that of 1b and 2b was saturated by 12 h.     

Resolution of β-unsaturated amines with isopropylidene glycerol hydrogen phthalate

1-Phenyl-2-propenylamine 2, 1-phenyl-2-propinylamine 3, 1-(1-cyclohexenyl)ethylamine 4, (E)-2-ethylidenecyclohexylamine 5 and α-methylallylamine hydrochloride 6 were selected as candidates for resolution with isopropylidene glycerol hydrogen phthalate 1, previously described as an efficient resolving agent of 1-arylalkylamines. With only the exception of 5, all these substrates were resolved by (S)-1. In particular both the enantiomers of 2 and 3 were obtained in excellent yields and with very high enantiomeric excesses. The absolute configurations of non-racemic forms of 2, 3 and 4, not prepared before except those of 3, were established by correlation with the respective hydrogenation products. The enantiomeric excesses of all the resolved substrates were accurately determined by chiral HPLC analysis. The fact that 1 resolves 4 and 6 but not their saturated analogues and shows higher efficiency in resolving 2 and 3 than 1-phenylpropylamine indicates the positive influence of the presence of β-unsaturation on the resolvability of aminic substrates with such an acid.     

Novel thiosemicarbazone derivatives containing benzimidazole moiety: Green synthesis and anti-malarial activity

A series of (E)-2-[5-chloro-1-(1H-benzo[d]imidazol-2-yl)ethylidene] N-(substituted) hydrazine carbothioamide (7a–7t) and (E)-2-[1-(1H-benzo[d]imidazol-2-yl)ethylidene] N-(substituted) hydrazine carbothioamide (8a–8t) were prepared via the synthesis of 1-(substituted-1H-benzimidazol-2-yl) ethanol (3a–3b) which was synthesized by the condensation of substituted o-phenylenediamine (2a–2b) with dl-lactic acid (1) followed by oxidation with sodium hypochlorite in mild acidic condition to form the corresponding ketones 4a–4b. Final compounds were formed by condensation of 4a–4b with different thiosemicarbazides 6a–6t. A total of 40 compounds were synthesized and characterized by FT-IR, ¹H NMR, ¹³C NMR, Mass spectral technique and elemental analysis, in addition they were evaluated for anti-malarial properties. Among the compounds tested 7o, 7p, 7q, 7r, 7s, 8e and 8h exhibited good antimalarial activity in vitro.     

Two novel abietane norditerpenoids with anti-inflammatory properties from the roots of Salvia miltiorrhiza var. alba

Salvialba acid (1) with a novel abietane norditerpenoid skeleton and 2-hydroxydihydrotanshinone I (2), a new abietane norditerpenoid, were isolated from Salvia miltiorrhiza var. alba. Their structures were elucidated by spectroscopic analysis and X-ray diffraction. The absolute configuration of 1 was determined by an electronic circular dichroism (ECD) experiment and TDDFT ECD computations. A possible biosynthesis pathway is proposed for 1. Compounds 1 and 2 were demonstrated to have anti-inflammatory effects on vascular inflammation induced by TNF-α in human aortic endothelial cells (HAECs).     

Fusopoltide A and fusosterede A,A polyketide with a pentaleno[1,2-c]pyran ring system and A degraded steride,from the fungus Fusarium solani

Fusopoltide A (1), a novel polyketide featured a pentaleno[1,2-c]pyran ring, and fusosteride A (2), a new steride with A/B-ring degraded, together with a known ergosterol peroxide (3), were isolated from a solid culture extract of Fusarium solani. The structures of 1 and 2 were elucidated by detailed interpretation of their HRESIMS and NMR spectroscopic data and their absolute configurations were determined by X-ray crystallographic analysis and the electronic circular dichroic (ECD) method, respectively. The postulated biogenetic pathways of 1 and 2 were also discussed. Compound 1 exhibits inhibitory activity against cyclooxygenase-2 (COX-2) with an IC₅₀ value of 3.45?μM.     

Diphenyl N-halosulfilimines : Preparation,decomposition, and reactions with nucleophiles

Diphenyl N chloro (l)-N bromo (2) and N-iodo-sulfilimines (3) were prepared by halogenation of diphenyl free sulfilimine. Compound 1 decomposed in benzene at room temperature. The decomposition of 1 is a chain reaction since the reaction was induced by chlorine or t-butyl hypochlorite affording diphenyl(diphenylsulfilimino) sulfonium chloride(4a) while it was inhibited by styrene or stilbene. Compound 4a was also obtained by the reaction of 1 with diphenyl sulfide in benzene. Decomposition of 1 in acetic acid proceeded smoothly affording various products. Compound 1 reacted with sulfides sulfoxides triarylphosphines and triethylamine affording the N-substituted iminosulfonium salts. Compounds 1 and 2 were hydrolyzed with sodium hydroxide affording diphenyl sulfoximine. The reaction of 1 with sodium cyanide gave diphenyl N cyanosulfilimine(17). The reaction of 1 with Grignard reagent gave diphenyl free sulfilimine. Compounds 2 and 3 are more stable than 1. Decomposition of 2 in benzene or acetic acid gave diphenyl(diphenylsulfilimino)sulfonium perbromide(4c)     

Xylyl derived oxacalixcrowns：Synthesis and crystal structure

Oxacalixcrowns 1, 2 and 3 were synthesized via reactions of dihydroxyoxacalix[2]arene[2]pyrazine 5 with ortho-, meta- and para-bis(bromomethyl)benzenes in a 1:1 fashion. The structures and conformations of 1, 2 and 3 were established by a combination of NMR, mass spectroscopies and single crystal X-ray diffraction analysis.     

4Z- and 4E-12-deoxydihydrokromycins,two naturally occurring kromycin aglycones of pikromycin from Streptomyces sp.

HPLC–UV guided isolation for the culture broth extract of the marine-derived bacterium Streptomyces sp. has led to the two 14-membered macrolides, 4Z- (1) and 4E-12-dehydroxykromycins (2). The chemical structures of compounds 1 and 2 were elucidated by spectral data, while the absolute stereochemistry of 1 and 2 were determined by application of circular dichroism (CD) and analysis of X-ray crystallographic data.     

Diaporthols A and B: Bioactive diphenyl ether derivatives from an endophytic fungus Diaporthe sp.

Diaporthols A (1) and B (2), two diphenyl ether derivatives, were isolated from cultures of an endophytic fungus Diaporthe sp. ECN-137 obtained from the leaves of Phellodendron amurense. The structures of 1 and 2 were determined by extensive spectroscopic analyses, and the structure of 2 was confirmed by X-ray crystallographic analysis. Compounds 1 and 2 showed anti-migration activities in TGF-β1-elicited MDA-MB-231 breast cancer cells at a concentration of 20?μM.     

Synthesis and biological evaluation of some novel-3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines

<正>The synthesis of a new series of 3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines(6a-h) was achieved in excellent yields by the condensation of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones(5a-h) with hydroxylamine at room temperature.These 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones(5a-h) were obtained by the condensation of 2-acetyl benzimidazoles(4a-d) with different aromatic aldehydes,which in turn were obtained by the oxidation of 2-(α-hydroxy) ethyl benzimidazoles(3a-d) prepared by the reaction of o-phenylenediamines(1a-d) withα-hydroxy propionic acid 2. The synthesized compounds were characterized by their IR,~1H NMR and MS analyses.These compounds were screened for their antibacterial and antifungal activity by standard methods and found some of them active.     

On the syntheses and photochemical properties of heterocyclic ketones as photosensitizers

The syntheses, and the electrochemical and photochemical properties of the fluorenone analogues 9H-pyrrolo[1,2-a]indole-9-one (1), and 9H-pyrido[3,4,b] pyrrolizin-9-one (2), which absorb in the visible region (ε^400nm = 4711 mol⁻¹ cm⁻¹ for 1 and ε^400nm = 872 1 mol cm⁻¹ for 2), are described. 9-Fluorenone as well as compounds 1 and 2 were able to reduce methyl viologen in the presence of 2-propanol under irradiation with UV light (λ⪢ 280 nm). Compounds 1 and 2 showed an interesting absorption and fluorescence behavior depending on concentration, solvent and pH value. Aqueous solutions of compound 1 gave two fluorescence maxima at 395 and 478 nm, when excited by λ^EX = 302 and 368 nm, respectively. In contrast, aqueous solutions of compound 2 showed only one emission maximum at 417 nm (excited by λ^EX = 296 or 378 nm). Fluorescence quantum yields (solvent: propanol, excitation wavelength λ^Ex = 436 nm) for compounds 1 and 2 were 0.2%. Compounds 1 and 2 showed irreversible reduction potentials at −850 and −560 mV (vs NHE), respectively. The results were compared with benzophenone and 9-fluorenone.     

Absolute configuration of 2-methoxy-2-(2-naphthyl)propionic acid as determined by the 1H NMR anisotropy method

2-Methoxy-2-(2-naphthyl)propionic acid 1 and 2-hydroxy-2-(2-naphthyl)propionic acid 2 were prepared by the Grignard reaction of 2-naphthylmagnesium bromide with (1R,2S,5R)-(−)-menthyl pyruvate. The absolute configurations of (+)-1 and (+)-2 were determined to be S by the ¹H NMR anisotropy method.     

Transformations of enaminones. A simple one-pot synthesis of imidazolone derivatives

Ethyl (5-benzoyl-2-oxo-3-substituted-2,3-dihydro-1H-imidazol-1-yl)carbamates 7 were prepared by the Michael addition of diethyl azodicarboxylate (3) to (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one (2) followed by substitution of the dimethylamino group with primary amines 5a–n to afford a mixture of (E) and (Z) diethyl 1-(1-(substituted)amino)-3-oxo-3-phenylprop-1-en-2-yl)hydrazine-1,2-dicarboxylates (6a–n), followed by cyclization to give final products 7a–n. The intermediate 6i was isolated and characterized and transformed into 7i. All imidazolones 7a–n were synthesized in one pot reaction sequences with individual reactions being very clean.     

Belamcandanes A and B,two unprecedented tricyclic-iridal triterpenoids from Belamcanda chinensis

Two unprecedented tricyclic-iridal triterpenoids, belamcandanes A–B (1–2), have been isolated from the rhizomes of Belamcanda chinensis. The structures of 1 and 2 were assigned by interpretation of spectroscopic data including NMR and MS, and their absolute configurations were assigned by ECD calculation. Compounds 1–2 possess a spiro[4,5]decane core structure and a α-terpineol moiety, representing the first example of tricyclic-iridal triterpenoids. The plausible biogenetic pathway for 1 and 2 is also proposed.     

Tsaokols A and B,unusual flavanol-monoterpenoid hybrids as α-glucosidase inhibitors from Amomum tsao-ko

Tsaokols A (1) and B (2), two complicated flavanol-monoterpenoid hybrids, were isolated from the dried fruits of Amomum tsao-ko under the guidance of LCMS and bioassay. Their structures were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 shared a flavanol backbone fused with 5/7 and 5/6 bicyclic monoterpenoid scaffolds, which were biogenetically condensed by Michael addition and acetalization. Compounds 1 and 2 exhibited significant α-glucosidase inhibitory activity with IC₅₀ values of 18.8 and 38.6 μmol/L (acarbose, IC₅₀ = 213 μmol/L). Docking study supported the strong interactions of 1 and 2 bonding with enzyme by mainly hydrophobic and hydrogen-bond effects. Compounds 1 and 2 could be fast distinguished by the diagnostic ions at m/z 289 and 313 in negative MS² experiments.