Pyrrole alkaloids from Bolbostemma paniculatum

Three pyrrole alkaloids were isolated from Bolbostemma paniculatum. Their structures were elucidated as 4-(2-formyl-5-methoxymethylpyrrol-1-yl)butyric acid methyl ester (1), 2-(2-formyl-5-methoxymethylpyrrol-1-yl)-3-phenylpropionic acid methyl ester (2) and alpha-methyl pyrrole ketone (3) by spectroscopic techniques. Among them, 1 and 2 are new compounds.     

Identification of new pyrrole alkaloids from the fruits of <Emphasis Type="Italic">Lycium chinense</Emphasis>

Three new minor pyrrole alkaloids, 3-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]pentanedioic acid (1), (2R)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-1-methoxy-1-oxobutanoic acid (2), and methyl (2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-4-methylpentanoate (3) were isolated from the fruits of Lycium chinense Miller (Solanaceae), along with the known compound, methyl (2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate (4). The structures of 1–4 were elucidated by analysis of their 1D- and 2D-NMR and HRMS data. The absolute configurations of 2–4, possessing a stereogenic center in each structure, were determined by comparison of their experimental electronic circular dichroism (ECD) with those of calculated ECD values.     

群海绵Agelas sp.的化学成分研究

目的 研究海绵Agelas sp.的化学成分。方法 运用乙醇提取、硅胶、Sephadex-LH₂₀色谱柱、HPLC等多种方法进行分离和纯化,根据理化性质和波谱数据进行结构鉴定。结果 分离得到9个化合物,经结构鉴定分别为4,5-二溴吡咯-2-甲酰胺（1）、4,5-二溴吡咯-2-甲酸（2）、4,5-二溴吡咯-2-甲酸甲酯（3）、N-（4,5-二溴-2-吡咯甲酰基）甘氨酸甲酯（4）、1-（4,5-二溴-2-吡咯甲酰胺基）丙酸甲酯（5）、1-（4,5-二溴-2-吡咯甲酰胺基）丙酸乙酯（6）、异吲哚-1,3-二酮（7）、2（3H）-苯并噻唑酮（8）和manzacidin C（9）。结论 化合物4~9为首次从该属海绵中分离得到,其中化合物4~6为新天然产物。     

Synthesis and biological activity studies of new hybrid molecules containing tryptamine moiety

The synthesis of N′-(4-substitutedphenylsulfonyl)-2-{4-[2-(1H-indol-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazides (3a–c), 2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N′-aryl methylidene acetohydrazides (4a–f) and 4-[2-(1H-indol-3-yl)ethyl]-5-(4-substitutedbenzyl)-2-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a, b) was performed starting from the corresponding acid hydrazides (2a, b) which was reported earlier. The treatment of 1,3,4-oxadiazole derivatives (5a, b) with hydrazine hydrate produced 4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl derivatives (6a, b). Then, compound 6b was converted to the corresponding Schiff base (7) by the treatment with anisaldehyde. The synthesis of 5-(4-chlorobenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (8) and 5-(4-methylbenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (10) was carried out by the reaction of acid hydrazides (2a, b) with aryl iso(thio)cyanates either via the formation of the intermediates (9a, b) (for 10) or direct cyclization (for 8). 1,3-Oxa(thia)zol-2(3H)-ylidene]acetohydrazide derivatives (11a, b) were obtained by the reaction of 9a, b with 4-chlorophenacyl bromide. All newly synthesized compounds were screened for their antimicrobial activities and some of which was found to be active against the test microorganisms.     

Conjugates of an abscisic acid derivative and phenolic glucosides,and a new sesquiterpene glucoside from <Emphasis Type="Italic">Lindera strychnifolia</Emphasis>

Three conjugates of the abscisic acid derivative (2Z,4E)-5-[(1S,3S,5R,8S)-3,8-dihydroxy-1,5-dimethyl-7-oxo-6-oxabicyclo[3.2.1]octan-8-yl]-3-methylpenta-2,4-dienoic acid and phenolic glucosides (1–3), and an eremophilane-type sesquiterpene glucoside (4), along with ten known compounds, were isolated from the roots of Lindera strychnifolia. The structures of all compounds were elucidated by means of spectroscopic analysis, and by application of the modified Mosher’s method for the methyl ester of the abscisic acid derivative and the octant rule for 4.     

A new highly oxygenated pregnane and two new 5-hydroxymethylfurfural derivatives from the water decoction of Poria cocos

Abstract

A new highly oxygenated pregnane steroid, pregn-7-ene-2β,3α,15α,20-tetrol (1) and two new 5-hydroxymethylfurfural derivatives, (5-formylfuran-2-yl)methyl 2-hydroxypropanoate (2) and (5-formylfuran-2-yl)methyl 2-(4-hydroxyphenyl)acetate (3), together with four known compounds, were isolated from the water decoction of Poria cocos. Their structures were established on the basis of extensive spectroscopic analysis. Compound 1 showed moderate inhibitory activity and a known compound (3S,6S)-3-[(1R)-1-hydroxyethyl]-6-(phenylmethyl)-2,5-piperazinedione (5) showed weak inhibitory activity against α-glucosidase, respectively.     

Synthesis and antibacterial evaluation of 6-azapyrimidines with α-methylene-γ-(4-substituted phenyl)-γ-butyrolactone pharmacophores

Abstract  

A series of 6-substituted 2-[(4-methylene-5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-diones (5, 6) and 2,4-bis[(4-methylene-5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-diones (9, 10) were designed, synthesized, and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. The synthesis of these compounds involved the Reformatsky-type reaction between ethyl α-(bromomethyl)acrylate and the proper ketones. Among these compounds, 2-[(4-methylene-5-oxo-2-phenyl tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-dione (5a) is the most active compound and shown the selective inhibition activity against Proteus vulgaris.     

A new sesquiterpene lactone glycoside and a new quinic acid methyl ester from Patrinia villosa

A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.     

A new chromone and a new aliphatic ester isolated from Daldinia eschscholtzii

Abstract

A new chromone and a new aliphatic ester were isolated from the EtOAc extract of myceliums of Daldinia eschscholtzii. Their structures were elucidated as (R)-5-hydroxy-8-methoxy-2-methylchroman-4-one (1) and (E)-6-(non-3-en-1-yl) -2H-pyran-2-one (2) by interpretation of the spectroscopic evidence.     

Identification,characterization and synthesis of impurities of zafirlukast

Zafirlukast is a drug in the treatment of pulmonary disorders such as asthma. During the process development of zafirlukast, five unknown impurities were detected at levels of below 0.10% (ranging from 0.05 to 0.15%) in reverse phase gradient high performance liquid chromatography (HPLC) method. The molecular weights were determined by LC–MS analysis. These impurities were isolated from crude samples of zafirlukast using gradient reverse phase preparative HPLC and were subsequently synthesized. Based on the spectral data, the structures of these impurities were characterized as 3-methoxy-4-(5-methoxycarbonylamino-1-methyl-1H-indol-3-ylmethyl)-benzoic acid (Impurity 1), {3-[2-methoxy-4-(toluene-2-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indol-5-yl}-carbamic acid methyl ester (Impurity 2), {3-[2-methoxy-4-(toluene-3-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indol-5-yl}-acetic acid cyclopentyl ester (Impurity 3), {3-[2-methoxy-4-(toluene-4-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indol-5-yl}-acetic acid cyclopentyl ester (Impurity 4), and 4-(5-cyclopentyloxy carbonylamino-1-methyl-1H-indol-3-yl methyl)-3-methoxy-benzoic acid methyl ester (Impurity 5). The separation of the impurities by reverse phase HPLC, the confirmation of their structures by IR, MS and NMR spectral data, the mechanism of their formation and their syntheses are discussed in detail.     

Synthesis of 4-(2,4-dioxo-5-pyrimidyl)-1,4-dihydropyridine derivatives

Hantzsch synthesis of 5-formyluracil (1), methyl acetoacetate (2) and methyl 3-aminocrotonate (3) gave 2,6-dimethyl-4-(2,4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3, 5-dicarboxylic acid dimethylester (4a) in 54.6% yield. As the same procedure, 1,3-dimethyl-5-formyl-uracil (6) gave 2,6-dimethyl-4-(1,3-dimethyl-2,4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (7a) in 52.2% yield.4a was methylated to afford7a also in 52% yield.     

Two new aromatic compounds from the resin of Styrax tonkinensis (Pier.) Craib

Two new aromatic compounds, trans-(tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-5-oxofuran-3-yl)methyl benzoate (1), 3-(4-hydroxy-3-methoxyphenyl)-2-oxopropyl benzoate (2) and one new natural product, 4-((E)-3-ethoxyprop-1-enyl)-2-methoxyphenol (3) together with five known aromatic compounds have been isolated from the resin of Styrax tonkinensis (Pier.) Craib. Their structures were determined by physical and spectroscopic methods.     

Potential antitumor α-methylene-γ-butyrolactone-bearing nucleic acid base. 3. Synthesis of 5′-Methyl-5′-[(6-substituted-9H-purin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans

Search for a new α-methylene-γ-butyrolactone-bearing 6-substituted purine as a potental antitumor agent has led to synthesize seven, hitherto unreported, 5′-Methyl-5′-[(6-substituted-9H-purin-9-yl)methyl]-2′-oxo-3′ methylenetetrahydrofurans (H, Cl, I, CH₃, NH₂, SH, >C=O) (6a-g). These include 5′-Methyl-5′-[(9H-purin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6a), 5′-Methyl-5′-[(6-chloro-9H-purin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6b), 5′-Methyl-5′-[(6-iodo-9H-purin-9-yl) methyl]-2′-oxo-3′-methylenetetrahydrofurans (6c), 5′-Methyl-5′-[(6-methyl-9H-purin-9-yl) methyl]-2′-oxo-3′-methylenetetrahydrofurans (6d), 5′-Methyl-5′-[(9H-adenin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6e), 5′-Methyl-5′-[(6-mercapto-9H-purin-9-yl) methyl]-2′-oxo-3′-methylenetetrahydrofurans (6f) and 5′-Methyl-5′-[(9H-hypoxanthin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6g) which were made by the Reformatsky-type reaction of ethyl α-(bromomethyl) acrylate with the corresponding (6-substituted-9H-purin-9-yl)-2-propanone intermediates (5a-g). These ketone intermediates5a-g, 1-(9H-purin-9-yl)-2-propanone (5a), 1-(6-chloro-9H-purin-9-yl)-2-propanone, (5b), 1-(6-iodo-9H-purin-9-yl)-2-propanone (5c), 1-(6-methyl-9H-purin-9-yl)-2-propanone (5d), 1-(9H-adenin-9-yl)-2-propanone (5e), 1-(6-mercapto-9H-purin-9-yl)-2-propanone (5f), and 1-(9H-hypoxanthin-9-yl)-2-propanone (5g) were directly obtained by the alkylation of the 6-substituted purine bases with the chloroacetone in the presence of K₂CO₃ (or NaH) under DMF (or DMSO). The preliminary in vitro cytotoxcity assay for the synthetic α-methylene-γ-butyro-lactone compounds (6a-g) were determined against three cell lines (PM-3A, P-388, and K-562) and showed the moderate antitumor activity (IC₅₀ ranged from 1.4 to 4.3 μg/ml) with the compound 5′-methyl-5′-[(9H-hypoxanthin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofuran (6g) showing the least antitumor activity.     

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2′-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-β-D-allopyranosyl-ferulate (3), and methyl-4-β-D-gulopyranosyl-cinnamate (4), along with six known compounds (5–10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC₅₀ values of 9.13 and 19.94 μM, respectively.     

New glycosides from <Emphasis Type="Italic">Dracocephalum tanguticum</Emphasis> maxim

Four new glycosides, luteolin-7-methoxy-3′-O-(3″-O-acetyl)-β-D-gluco pyranuronic acid-6″-methyl ester (1), benzyl-6-[(2E)-2-butenoate]-β-D-glucopyranoside (2), 2-methoxy-4-(2-propen-1-yl)penyl-6-acetate-β-D-glucopyranoside (3), and 2-methoxy-4-(2-propen-1-yl)penyl-6-[(2E)-2-butenoate]-β-D-glucopyranoside (4), along with benzyl-β-D-glucopyranoside (5), 2-methoxy-4-(2-propen-1-yl)penyl-β-D-glucopyranoside (6), and pectolarigenin (7), were isolated from the whole plant of Dracocephalum tanguticum Maxim. The structures of 1-4 were elucidated by detailed spectroscopic analyses, including HR-ESI-MS and 2D NMR spectroscopic data. The inhibitory effects against nitric oxide production in LPS-stimulated RAW264.7 cells of all seven compounds were also evaluated.     

Synthesis and antimicrobial activity of new 1-[(tetrazol-5-yl)methyl] indole derivatives,their 1,2,4-triazole thioglycosides and acyclic analogs

New 1-[(tetrazol-5-yl)methyl]indole derivatives, their acyclic nucleoside analogs and the corresponding glycoside derivatives were synthesized. Furthermore, the [)(1,2,4-triazol-3-yl)methyl])-2H-tetrazole derivative as well as the corresponding thioglucoside were prepared. The synthesized compounds were tested for their antimicrobial activity against Aspergillus Niger, Penicillium sp, Candida albican, Bacillus subtilis, Streptococcus lacti, Escherichia coli, Pseudomonas sp., and streptomyces sp. Compounds 3, 5 and 19b exhibited potent antibacterial activity and compounds 4, 5 and 10 exhibited high activities against the tested fungi compared with fusidic acid.     

Total synthesis and cytotoxic activity of stellatin

Stellatin (3,4-dihydro-8-hydroxy-7-hydroxymethyl-6-methoxyisocoumarin) (8), an extrolite of fungal genera Emericella and Aspergillus, was synthesized. Thus, Vilsmeier–Haack formylation of methyl ester of 3,5-dimethoxy-4-methylphenylacetic acid (1) to afford the formyl ester (2) followed sulfamic acid–sodium chlorite oxidation of the aldehydic function to yield the carboxy ester (3). Chemoselective reduction of ester function in the latter using NaBH₄/THF/MeOH furnished the corresponding hydroxy acid (4) that on cyclodehydration afforded the 3,4-dihydro-6,8-dimethoxy-7-methylisocoumarin (5). Benzylic bromination of the C-7 methyl in 5 using NBS/benzoyl peroxide to give the 7-bromomethyldihydroisocoumarin (6) followed the nucleophilic substitution using aqueous acetone to provide 7-hydroxymethyl-dihydroisocoumarin (7). Finally, the regioselective demethylation of 8-methoxyl group using anhydrous magnesium iodide furnished the stellatin (8). The dihydroisocoumarins (5–8) were screened for cytotoxic activity against human keratinocyte cell line and were found to exhibit moderate to good activity.     

Triterpenoids from Peganum nigellastrum

Two triterpenoids were isolated from the roots of Peganum nigellastrum Bunge. Their structures were elucidated as 3α-acetoxy-27-trans-caffeoyloxyolean-12-en-28-oic acid methyl ester (1) and 3-oxotirucalla-7, 24-dien-21-oic acid (2) on the basis of spectroscopic evidence. 1 is a new triterpene ester and 2 is a known compound isolated for the first time from genus Peganum.     

Two new polyprenylated acylphloroglucinols from Hypericum scabrum

Two new polyprenylated acylphloroglucinols, (1S,32R,5S,6R,7R)-6-((R)-3,4-di-hydroxy-4-methylpentyl)-2-(2-hydroxypropan-2-yl)-7-isobutyryl-6-methyl-5,9-bis(3-methylbut-2-en-1-yl)-4,5,6,7-tetrahydro-2H-32,7-methanocycloocta[b]furan-8,10(3H)-dione (1) and (4R,5R,7R)-4-((R)-3,4-dihydroxy-4-methylpentyl)-2,2,4-trimethyl-5,7-bis(3-methyl-but-2-en-1-yl)-7-(5-methylhex-4-enoyl)-4,5,6,7-tetrahydrobenzofuran-3(2H)-one (2) were isolated from Hypericum scabrum. The structures were elucidated by means of spectroscopic methods, including MS, IR, NMR, OR, and CD.     

Four new long-chain aliphatics from the feces of Trogopterus xanthipes

Chemical investigation of Trogopterus feces has led to the isolation of four new long-chain aliphatics, including two new fatty alcohols, 8,15-nonacosanediol (1) and 6,13-nonacosanediol (2), one new fatty acid ester, dihexyl 7,7′-oxydiheptanoate (3), and one new ceramide, (2R)-2-hydroxy-N-[(2S,3S,4R,11E)-1,3,4-trihydroxydocos-11-en-2-yl]heneicosanamide (4). Their structures were elucidated by means of chemical and extensive spectroscopic analysis. Compound 3 exhibited moderate activity of antithrombin in vitro.