Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects

In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by ¹H NMR, ¹³CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1–S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1–S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with K_is in the range of 1.79?±?0.22–2.73?±?0.08?nM against hCA I and in the range of 1.72?±?0.58–11.64?±?5.21?nM against hCA II, respectively.     

Novel steroidal saponins from Dioscorea esculenta (Togedokoro)

Fifteen steroidal saponins 1–15, which include 4 furostanol glycosides 1–3 and 15, and 11 spirostanol glycosides 4–14, were isolated from the tubers and leaves of lesser yam (Dioscorea esculenta, Togedokoro). Their structures were identified by nuclear magnetic resonance and liquid chromatography mass spectroscopy. Four steroidal saponins 9, 11, 14, and 15 were found to be novel compounds.     

New acylated anthocyanins from purple yam and their antioxidant activity

Purple yam (Dioscorea alata L.), which is widely distributed in tropical and subtropical regions, is characterized by its color and viscosity. Previous studies have shown that purple yams contain a variety of acylated anthocyanins that exhibit higher levels of antioxidant activity than the corresponding nonacylated compounds. In this study, the pigments found in purple yams from the Philippines (D. alata) were isolated and evaluated in terms of antioxidant activity. Four new acylated anthocyanins, alanins (1–4) were isolated from the MeOH extracts of purple yam, which were subsequently determined to be cyanidin (1, 2, and 4) and peonidin (3) type compounds, along with four known anthocyanins (5–8). The structures of 1–4 were determined by spectroscopic methods, including NMR and MS analyses. The antioxidant activities of anthocyanins 1–8 were investigated using oxygen radical absorbing capacity and ferric reducing antioxidant power assays.     

一株红树林曲霉菌Aspergillus sp.WHUF0343的次级代谢产物研究

【目的】研究分离自三亚亚龙湾红树林根系土壤的真菌Aspergillus sp. WHUF0343的次级代谢产物及其生物活性。【方法】利用硅胶柱层析、Sephadex LH-20凝胶柱层析和半制备高效液相色谱等技术对该菌的发酵产物进行分离纯化;综合利用核磁共振波谱(NMR)和质谱(MS)等现代波谱技术以及与文献数据对照确定化合物的结构;分别采用肉汤微量稀释检测法和MTS法对化合物进行抗菌和肿瘤细胞毒活性测试。【结果】从真菌Aspergillus sp.WHUF0343的发酵产物共分离并鉴定了10个化合物,分别为isoechinulin A (1)、neoechinulin A (2)、neoechinulin E (3)、preechinulin (4)、neoechinulin D (5)、variecolorin J (6)、dehydroechinulin (7)、questinol (8)、emodin (9)和catenarin (10)。活性评价显示化合物2、9和10对幽门螺杆菌(Helicobacter pylori)和金黄色葡萄球菌(Staphylococcus aure...     

SYNTHESIS OF 4-ACYL-1H-1,2,3-TRIAZOLIC NUCLEOSIDES

Two simple regiospecific methodologies based on triazolic ring construction in the course of synthesis were applied for the synthesis of 1,2,3-triazolic nucleoside analogues. The cycloaddition reactions between diazomalonaldehyde and appropriate glycosylamine derivatives were rather effective, producing the desired nucleosides 11, 17 and 24. Diazotization of enamines 21a and 21b led to the corresponding triazolic ribonucleoside derivatives 22a and 22b, in good yields. Deprotection reaction of 22a, 22b and 24 was easily achieved by Lewis acid catalysis, producing the corresponding ribonucleosides 23a, 23b and 25.     

Synthesis of N-Aryl Uracils and Hypoxanthines and Their Biological Properties

Abstract

1-Benzyluracils 2a,b were treated with iodobenzene in the presence of cuprous oxide in 2,4,6-trimethylpyridine at 180°C to give the N ¹-phenyl derivatives 3a and 3b in 47% and 55%, respectively. Similar reaction of 2a with 2-bromopyridine at 120°C gave the 3-(2-pyridinyl)uracil 4a in 42% yield. However, unusual product 5 as well as 3-(2-pyridinyl) derivative 4b were obtained in the case of 2b. The structure of 5 was identified as 1-(2,6-difluorobenzyl)-3-[(2,4-dimethyl-2-pyridinyl)methyl]uracil from spectroscopic data. Reaction of the hypoxanthines 7a,b with 2-bromopyridine gave the 1-(2-pyridinyl)hypoxanthines 8a,b in low yields. But N-phenylation of 7a,b were unsuccessful.     

New triterpene oligoglycosides from the Caribbean sponge Erylus formosus

Seven new triterpene glycosides, erylosides R₁ (1), T₁ (3), T₂ (4), T₃ (5), T₄ (6), T₅ (7), and T₆ (8) along with the known formoside (2) were isolated from the sponge Erylus formosus collected along the Caribbean coast of Mexico. Glycoside 1 was determined as a trisaccharide, glycoside 2 as a tetrasaccharide while glycosides 3–8 were hexasaccharide. Their carbohydrate chains were unprecedented and have never been found in oligosaccharides from other biological sources, except Erylus spp. Three carbohydrate chains in the glycosides 3 and 6, 4 and 7, 5 and 8 correspondingly are new. The glycosides 1–5 have penasterol as aglycone while glycosides 6–8 proved to be glycoconjugates of 24-methylene-14-carboxy-lanost-8(9)-en-3β-ol.     

苦槛蓝叶的黄酮类成分及其荔枝霜疫霉抑制活性研究

为了解苦槛蓝(Myoporum bontioides)的化学成分,采用色谱分离法从叶中分离得到11个化合物,分别鉴定为：5,7,3’-三羟基-4’-甲氧基黄酮(1)、3,5,7,4’-四羟基-3’-甲氧基黄酮(2)、5,7,4’-三羟基-3’,5’-二甲氧基黄酮(3)、木犀草素(4)、山奈酚(5)、鼠李黄素(6)、5,7-二羟基二氢黄酮(7)、7,4’-二羟基二氢黄酮(8)、5,7,3’,4’-四羟基二氢黄酮(9)、5-O-乙酰基-3,7,3’,4’-四羟基二氢黄酮(10)和7-甲氧基香橙素(11)。除化合物4、7、11之外,其他化合物均为首次从苦槛蓝叶中分离得到。菌丝生长速率法测试表明化合物4、7～9和11对荔枝霜疫霉菌具有较好的抑菌活性。     

苦槛蓝叶中的黄酮类化合物

为了解苦槛蓝(Myoporum bontioides A.Gray)的化学成分,采用色谱分离技术从苦槛蓝叶片中分离得到11个黄酮类化合物。通过波谱分析,他们的结构分别鉴定为:桔皮素(1)、甜橙素(2)、5,4′-二羟基-6,7,8,3′-四甲氧基黄酮(3)、4′,5,7,8-四甲氧基黄酮(4)、去甲基川陈皮素(5)、5-羟基-6,7,3′,4′-四甲氧基黄酮(6)、3′,4′,5,6,7,8-六甲氧基黄酮(7)、二氢山柰酚(8)、木犀草素(9)、3′,4′,5,7-四羟基-3-甲氧基黄酮(10)和芹黄素(11)。除化合物9之外,其他化合物均为首次从苦槛蓝叶片中分离得到。孢子萌发法测定结果表明,化合物1,2,8和9对香蕉炭疽菌(Colletotrichum musae)具有较好的抑菌活性。这为苦槛蓝叶片中有效成分的利用提供了理论依据。     

Synthesis of the Fluoromethyl Derivatives of Carbocyclic Oxetanocin A

Abstract

Treatment of the 2,3-di-O-benzoate 1 with sodium boronhydride mainly afforded the 3-O-benzoate 2 accompanied with isomers 3a,b and fully deprotected product 4. Compound 2 was converted to 5, from which 8 was obtained. The 1-cyclobutanols 8 and 5 were successfully condensed with 6-chloropurine by Mitsunobu reaction to give 9 and 11, respectively. After partial deprotection, the cyclobutyl nucleosides 10 and 15 were subjected to fluorination using DAST to afford the fluoromethyl analogs 12 and 16 from which target compounds 14 and 17 were obtained in good yields, respectively.

     

Ordering selected Zn(II), Cu(II), Pd(II) and Co(III) complex compounds: their separately and combinedly antibacterial therapy and DNA-binding studies

Abstract

In this study, four Co(III)-, Cu(II)-, Zn(II)- and Pd(II)-based potent antibacterial complexes of formula K₃[Co(ox)₃]·3H₂O (I), [Cu(phen)₂Cl]Cl·6.5H₂O (II), [Zn(phen)₃]Cl₂ (III) and [Pd(phen)₂](NO₃)₂ (IV) (where ox is oxalato and phen is 1,10-phenanthroline) were synthesized. They were characterized by elemental analysis, molar conductivity measurements, UV–vis, Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (¹H-NMR) techniques. These metal complexes were ordered in three combination series of I+II, I+II+III and I+II+III+IV. Antibacterial screening for each metal complex and their combinations against Gram-positive and Gram-negative bacteria revealed that all compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV, and the activity of their combinations followed the order of I+II+III+IV > I+II+III > I+II. The DNA-binding properties of complex (I) and its three combinations were studied using electronic absorption and fluorescence (ethidium bromide displacement assay) spectroscopy. The results obtained indicated that all series interact effectively with calf thymus DNA (CT-DNA). The binding constant (K_b), the number of binding sites (n) and the Stern–Volmer constant (K_sv) were obtained based on the results of fluorescence measurements. The calculated thermodynamic parameters supported that hydrogen bonding and van der Waals forces play a major role in the association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series.

Communicated by Ramaswamy H. Sarma     

SYNTHESIS AND ANTIVIRAL EVALUATION OF N-GLYCOSIDES DERIVED FROM 6-AMINO-3-ARYL-2-METHYL-4-(3H)-QUINAZOLINONES

Reaction of monosaccharides (D-glucose, D-galactose, D-xylose or L-arabinose) with 6-amino-3-aryl-2-methyl-4-(3H) quinazolinones (1a–c) in boiling methanol yielded the corresponding N-glycopyranosides 3a–c, 4a–c, 5a,b and 6a,b. The N-glycopyranosides 3a–c, 4a–c, 5a,b and 6a,b were acetylated with acetic anhydride and pyridine to give the corresponding acetate derivatives 7a–c, 8a–c, 9a,b and 10a,b. The structures of all these glycosides were assessed by elemental analysis, IR, NMR and mass spectra. Some of these products were tested for anticancer and anti-AIDS activity.     

Community Structure,Geochemical Characteristics and Mineralogy of a Hypersaline Microbial Mat,Cabo Rojo,PR

Seasonal variations in precipitation changed the community composition and microbial activity in a hypersaline, tropical microbial mat, in Cabo Rojo, PR. Using a combination of dissection, light, and transmission electron microscopy, terminal restriction fragment length polymorphism (T-RFLP), in situ microelectrode studies, and ³⁵ S isotope incubations, we documented the major differences between wet and dry seasons. During the wet season (precipitation 177 mm), cyanobacterial (green layer) and anoxyphototrophic (pink layer) communities, as well as the black FeS layer were well-developed, and T-RFLP patterns indicated a diverse community. The rate of oxygenic photosynthesis was 49 μ M min ^{? 1} . Aerobic respiration was 29 μ M min ^{? 1} , and sulfate reduction was 264 nmol cm ^{? 3} h ^{? 1} . During the dry season (precipitation 51 mm), cyanobacteria and anoxyphototrophs were less diverse and abundant, and T-RFLP patterns were less complex. The O ₂ production rate was reduced to 9 μ M min ^{? 1} , as was O ₂ consumption (7 μ M min ^{? 1} ) and sulfate reduction (26 nmol cm ^{? 3} h ^{? 1} ). Aragonite, calcite, halite, and quartz were the predominant minerals. Seasonal differences were found in the green and pink layers for both halite and quartz. Gypsum was not observed, likely due to a sample handling artifact. The fluctuations in community composition and metabolic activity, principally reflected in fluctuations in binding and trapping potential of the uppermost mat community, might be responsible for the observed differences in mineralogy.     

Associations of Polymorphisms in Four Candidate Genes with Carcass and/or Meat-Quality Traits in Two Meat-Type Chicken Lines

The associations between polymorphisms of five genes, calpain 1 ( CAPN1 ), follicle stimulating hormone beta (FSHB), follicle stimulating hormone receptor (FSHR), peroxisome proliferator-activated receptor gamma (PPARG), and retinol binding protein 7 (RBP7), and live weight, carcass composition, and meat-quality traits were estimated from two meat-type chickens lines (n = 311). Except for the variants of the FSHR gene, 11 SNPs of the other four genes and two diplotypes of PPARG were associated with one or more traits excluding shear factor (SF). SNP C31566680T of the CAPN1 gene was significantly associated with live weight (LW) carcass traits. The SNP A4580859C of FSHB gene was significantly associated with breast muscle weight (BrW) and LW. One of the PPARG SNPs, C5070948T, was associated with intramuscular fat content in breast (IMF _br ). Diplotype P1 of the PPARG gene was significantly associated with LW and all carcass traits. P3 were significantly associated with abdominal fat weight (AbFW). SNPs in RBP7 were only associated with BrW. These results indicate that the four genes were associated with these traits and have promise as genetic markers for future marker-assisted selection. Supplementary materials for this paper are available online.     

A Convenient Synthesis of Acyclic Adenosines with an Unsaturated Side Chain by Modification of 9-(2,3-O-Isopropylidene-D-Ribityl)Adenine

Abstract

In expectation of discovering their antiviral activity, acyclic adenosine derivatives 7, 11, 12, and 16 were designed as analogs of neplanocin A (NPA) and L-eritadenine which are strong inhibitors of S-adenosyl-L-homocysteine hydrolase. The 1′,5′-seco-analog of 4′-deoxymethyl-NPA (DHCA) 7 was synthesized by dideoxygenation of 9-(2,3-O-isopropylidene-D-ribityl)adenine (2). Acyclic DHCA analogs 11 and 16 were obtained by Wittig reaction of the aldehyde 3 with Ph₃P=CHCO₂Et and Ph₃P=CHCN, respectively. Hydrolysis of the ester 11 afforded a vinylog of L-eritadenine 12. The synthesized acyclic nucleosides 7, 10, and 11 were evaluated for antiviral activity, however, none of them showed any significant antiviral activity.     

Synthesis of 2′,3′-Dideoxy- and 3′-Azido-2′,3′-dideoxy-pyridazine Nucleosides as Potential Antiviral Agents

Abstract

The synthesis of 4-methoxy-, 4-amino-3-chloro-, and 4-amino-1-(2,3-dideoxy-B-D-glycero-pentofuranosyl)pyridazin-6-one nucleosides, 6,19 and 20 is described. The synthesis of 3,4-dichloropyridazin-6-one (10) was accomplished in 44% overall yield using bromomaleic anhydride (17) as the starting material. The condensation of the silylated base of 10 with the halogenose 12 in the presence of trimethylsilyl triflate as a catalyst afforded a mixture of3,4-dichloro-1-(3,5-di-O-p-toluoyl-2-deoxy-B-D-erythro-pentofuranosyl)pyrridazin-6-one (13) in 67% and its α-anomer 14 in 12% yield, respectively. A series of 3′-sulfonate esters were prepared to explore the synthesis of 3-chloro-4-hydroxy-1-(3-azido-2,3-dideoxy-B-D-erythro-pentofuranosyl) pyridazin-6-one (32) via 6,3-anhydronucleoside analogues. Compounds 15, 19 and 20 were evaluated against human immunodeficiency virus, human cytomegalovirus, and herpes simplex virus type 1 but were inactive.     

Antimicrobial constituents of peel and seeds of camu-camu (Myrciaria dubia)

Various antimicrobial constituents of camu-camu fruit were isolated. Acylphloroglucinol (compound 1) and rhodomyrtone (compound 2) were isolated from the peel of camu-camu (Myrciaria dubia) fruit, while two other acylphloroglucinols (compounds 3 and 4) were obtained from camu-camu seeds. The structures of the isolated compounds were characterized by spectrophotometric methods. Compounds 1 and 4 were confirmed to be new acylphloroglucinols with different substituents at the C7 or C9 position of 2, and were named myrciarone A and B, respectively. Compound 3 was determined to be isomyrtucommulone B. This is the first report of the isolation of 3 from a natural resource. The antimicrobial activities of compounds 1, 3, and 4 were similar to those of 2, and the minimum inhibitory concentrations were either similar to or lower than that of kanamycin. These results suggest that the peel and seeds of camu-camu fruit could be utilized for therapeutic applications.     

Bioconversion composition of Ssanghwa-tang fermented by <Emphasis Type="Italic">Lactobacillus fermentum</Emphasis>

Ssanghwa-tang is a medicinal formula that is widely prescribed in Korea to decrease fatigue after an illness. Fermented herbal medicines might be made more efficacious than conventional herbal medicines by increasing the absorption and bioavailability of the active compounds. In this study, Ssanghwa-tang was fermented to produce bioconversion compositions using Lactobacillus fermentum, and six peaks were decreased, four peaks were increased and one peak newly appeared in the HPLC-DAD chromatogram. The structures of the newly-appearing compound (1) and increased (2–5) compounds were identified as follows using NMR and MS: liquiritigenin (1), nodakenetin (2), cinnamyl alcohol (3), decursinol (4), and benzoic acid (5). The decreased compounds were identified to be paeoniflorin (6), liquiritin (7), nodakenin (8), cinnamaldehyde (9), decursin (10), and decursinol angelate (11) using HPLC-DAD analysis with authentic compounds. The high performance liquid chromatography method was used to quantify the eleven constituents in Ssanghwa-tang and fermented Ssanghwa-tang. All calibration curves of the standard compounds exhibited excellent linearity with a R² > 0.9940.     

Synthesis and Antimicrobial Screening of Novel Thioglycosides and Acyclonucleoside Analogs Carrying 1,2,3-Triazole and 1,3,4-Oxadiazole Moieties

The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9–11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et₃N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K₂CO₃ in DMF yielded the corresponding acyclonucleoside analogs 16–18 and 23–25. The isopropylidenes 19 and acetyl derivatives 26–28 of the products were also prepared. The newly synthesized compounds were characterized by ¹H NMR, ¹³C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs.     

Stereoselective reduction of 2-azido-1-phenylethanone derivatives by whole cells of marine-derived fungi applied to synthesis of enantioenriched β-hydroxy-1,2,3-triazoles

Several marine-derived fungi were evaluated by the bioreduction of 2-azido-1-phenylethanone 1, and the strains A. sydowii CBMAI 935 and M. racemosus CBMAI 847 were selected for the reduction of 2-azido-1-phenylethanone derivatives 2–4. Whole cells of A. sydowii CBMAI 935 promoted the reduction of 2-azido-1-phenylethanones 1–4 with high selectivities to yield the (S)-2-azido-1-phenylethanols 1a–4a. Bioreduction of compounds 1–4 by M. racemosus CBMAI 847 led to (R)-2-azido-1-phenylethanols for 1, 2 and 4 and (S)-2-azido-1-phenylethanol 3. Enantiomerically enriched 2-azido-1-phenylethanols 1a–4a and phenylacetylene 5 were applied in the synthesis of β-hydroxy-1,2,3-triazoles using CuSO₄ and sodium ascorbate leading to regioselective formation of enantioenriched 1,4-disubstituted 1,2,3-triazole compounds 1b–4b.