N/C-4 substituted azetidin-2-ones: synthesis and preliminary evaluation as new class of antimicrobial agents

A series of 3-chloro-4-(3-methoxy-4-acetyloxyphenyl)-1-[3-oxo-3-(phenylamino)propanamido] azetidin-2-ones 3a-g and 3-chloro-4-[2-hydroxy-5-(nitro substituted phenylazo)phenyl]-1-phenylazetidin-2-ones 6a-h were synthesized using appropriate synthetic route. Structures of all the synthesized compounds were established on the basis of elemental analysis and spectroscopic data. The antimicrobial activity of the synthesized compounds was screened against several microbes. Several of these molecules showed potent antimicrobial activity against Bacillus anthracis, Staphylococcus aureus and Candida albicans and significant structure-activity relationship (SAR) trends.     

Synthesis of protected peptides with the sequence 8-13-1-3 and 4-13-1-3 of mycobacillin and their analogs

We have synthesized both a protected nonapeptide of the mycobacillin 8-13-1-3 amino acid sequence and a protected tridecapeptide of the 4-13-1-3 sequence, which are a fragment and a open chain analog of this antibiotic, respectively. Some of their analogs with a reversed configuration of the amino acids at fixed positions have also been synthesized. The nonapeptides were obtained by coupling partially protected mycobacillin fragments with the sequence 8-10 and 11-13-1-3 while the tridecapeptides were synthesized by coupling partially protected fragments 4-7 and 8-13-1-3. Configuration analogs of these fragments were also used. The coupling methods applied were DCCI/HONSu or DCCI/HOBt. The purification of the synthesized peptides was achieved by means of recrystallization or column chromatography on silica gel. They were characterized mainly by m.p., degree of optical rotation, elemental and amino acid analysis.     

Anti-barnacle activity of novel simple alkyl isocyanides derived from citronellol

Twenty novel simple alkyl isocyanides derived from citronellol were synthesized and evaluated for their antifouling activity and toxicity against cypris larvae of the barnacle, Balanus amphitrite. The anti-barnacle activity of the synthesized isocyanides was in the EC(50) range of 0.08-1.49 μg ml(-1). Simple isocyanides containing a benzoate and chloro group showed the most potent anti-barnacle activity. In addition, none of the synthesized compounds showed significant toxicity and LC(50) values were <10 μg ml(-1). The LC(50)/EC(50) ratios of almost all of the synthesized compounds were >10(2). The results indicate that these simple isocyanides are promising low-toxicity antifouling agents.     

Enantioselective synthesis of ancepsenolide and its analogs

Ancepsenolide (1a-s) and the enantiomer (1a-r) were respectively synthesized from (S)- and (R)-2-[(R)-O-MEM-mandeloyloxylpropanal (3a-s and 3a-r) and diisopropyl hexadecanedioate (5). The analogs (1b, 2a and 2b) were synthesized by a similar method.     

Comparison of two β-glucosidases for the enzymatic synthesis of β-(1-6)-β-(1-3)-gluco-oligosaccharides

A domain of epiglucan was synthesized by beta-glucosidases. Two beta-glucosidases, an extracellular beta-glucosidase derived from Sclerotinia sclerotiorum grown on xylose, and a commercial lyophilized preparation of beta-glucosidase from Aspergillus niger, were used to synthesize gluco-oligosaccharides from cellobiose and, specially, beta-(1-6) branched beta-(1-3) gluco-oligosaccharides, corresponding to the structure of epiglucan. Gentiobiose, cellotriose, cellotetraose, beta-Glc-(1-3)-beta-Glc-(1-4)-Glc, beta-Glc-(1-6)-beta-Glc-(1-4)-Glc and beta-Glc-(1-6)-beta-Glc-(1-3)-Glc were synthesized from cellobiose by both enzymes. The latter compound was preferentially synthesized by the beta-glycosidase from Sclerotinia sclerotiorum. Under the best conditions, only 7 g l(-1) of beta-Glc-(1-6)-beta-Glc-(1-3)-Glc was synthesized by the beta-glycosidase from Aspergillus niger compared to 20 g l(-1) synthesized with beta-glycosidase from Sclerotinia sclerotiorum.     

Further Syntheses of Lindane Analogs

dl-(1245/36)-4,5,6-Trichloro-l,2,3-trimethoxycyclohexane and dl-(1245/36)-2,3,4,5,6-penta-chloro-1-methylthiocyclohexane were synthesized from (1245/36)-3,4,5,6-tetrachlorocyclo-hexane-1, 2-diol. dl- (1245/36) -1, 4, 5, 6-Tetrachloro-2-methoxy-3-methylthiocyclohexane and dl-(1245/36)-l,4,5,6-tetrachloro-2,3-dimethoxycyclohexane were synthesized from (12345/6)-1, 4, 5, 6-tetrachloro-2, 3-epoxycyclohexane. meso- (1245) -1,2,4,5-Tetrachlorocyclohexane was synthesized from benzene via cyclohexadiene-1,4.     

Synthesis and urease enzyme inhibitory effects of some dicoumarols

Dicoumarols 1-10 with substituted phenyl residues at C-11 were synthesized and screened for their urease inhibition effects. All synthesized compounds showed varying degree of urease inhibitory activity ranging from IC50 = 74.30-91.35 microM.     

Synthesis of the four stereoisomers of 3,12-dimethylheptacosane, (Z)-9-pentacosene and (Z)-9-heptacosene,the cuticular hydrocarbons of the ant,Diacamma sp.

All of the four stereoisomers of 3,12-dimethylheptacosane were synthesized from the enantiomers of citronellal. (Z)-9-Pentacosene and (Z)-9-heptacosene were also synthesized. These hydrocarbons are the characteristic components of the cuticular hydrocarbons of the queen of the ant, Diacamma sp..     

Effect of N,N'-Diphenyl-p-phenyl-enediamine (DPPD) on Serum Triglyceride and Lipoprotein Cholesterol in Rats

Ancepsenolide (1a-s) and the enantiomer (1a-r) were respectively synthesized from (S)- and (R)-2-[(R)-O-MEM-mandeloyloxy]propanal (3a-s and 3a-r) and diisopropyl hexadecanedioate (5). The analogs (1b, 2a and 2b) were synthesized by a similar method.     

Synthesis and hybridization property of sugar and phosphate linkage modified oligonucleotides.

1-[3-Deoxy-5-O-(4,4'-dimethoxytriphenylmethyl)-3-C-hydroxymethyl-2 -O-(2-methoxyethoxymethyl)-beta-D-erythro-pentofuranosyl]thymine (13) was synthesized from 1,2-isopropylidene-D-xylose (1) as a building block of modified oligonucleotides. Three types of novel oligonucleotides were synthesized from 13 and their T(m)s were compared with those of the corresponding natural oligonucleotides. It was found that our synthesized oligomers had lower affinity to DNA and RNA than the natural oligomers.     

Synthesis and preliminary screening of novel N-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}acetamides as potential atypical antipsychotic agents

A series of N-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}acetamides were synthesized as prospective novel atypical antipsychotic agents. Microwave irradiation of acetyl glycine (I) with substituted piperazines in the presence of DCC in DMF for about 3-5 min gave the titled compounds (P:1-7). All the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. D(2) antagonism studies were performed using the climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine induced head twitches in mice. Among the synthesized compounds P4 was found to be the most active compound.     

Design and synthesis of novel inhibitors of human kynurenine aminotransferase-I

Herein we report 6-ethoxy-6-oxo-5-(2-phenylhydrazono) hexanoic acid and 3-(2-carboxyethyl)-1H-indole-2-carboxylic acid derivatives as synthetically accessible leads for human kynurenine aminotransferase-I (KAT-I) inhibitors. In total, 12 compounds were synthesized and their biological activities were determined using the HPLC-UV based KAT-I inhibition assay. Of the 12 compounds synthesized, 10 were found to inhibit human KAT-I and the most active compound was found to be 5-(2-(4-chlorophenyl) hydrazono)-6-ethoxy-6-oxohexanoic acid (9a) with an IC(50) of 19.8 μM.     

Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation

A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity.     

Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent

Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented.     

Design,Synthesis, Molecular Docking Studies,and Biological Evaluation of Pyrazoline Incorporated Isoxazole Derivatives

Russian Journal of Bioorganic Chemistry - A novel series of pyrazoline incorporated isoxazole derivatives were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR...     

Optical and Photocatalytic Measurements of Co-TiO2 Nanoparticle Thin Films

Plasmonics - Co-TiO2 nanoparticle thin films were synthesized by sol-gel method. The structural properties of the synthesized sample were studied using FTIR, XRD, and TEM. XRD confirmed the...     

Synthesis of vasoactive intestinal peptide (VIP) via the mixed anhydride method

Porcine VIP was synthesized from three segments. The segments, VIP(1-6), VIP(7-13), and VIP(14-28), were synthesized via the Repetitive Excess Mixed Anhydride (REMA) method. The low solubility of the C-terminal segment was greatly improved by a temporary substitution of Asn28 by a beta-t-butyl aspartic acid ester. The segments VIP(1-6) and VIP(7-13) were purified by HPLC and coupled via the mixed anhydride method. The product was purified by gel filtration. VIP was synthesized from VIP(1-13) and VIP(14-28) by the same procedure. After deprotection, Met17-sulfoxide reduction, and purification by ion-exchange chromatography, the product was found to have the expected amino acid composition and biological potency. A HPLC purified sample was compared with several commercial preparations of varying purity.     

Potent antitumor activity of synthetic 1,2-Naphthoquinones and 1,4-Naphthoquinones

Rhinacanthone (1) and two 1,2-pyranonaphthoquinones (2,3) were synthesized and found to show very potent cytotoxicity against three cancer cell lines (KB, HeLa and HepG(2)) with IC(50) values of 0.92-9.63 microM, whereas the corresponding hydroxylated derivative 4 had reduced cytotoxicity (IC(50) values of 7.61-24.13 microM). Three 1,2-furanonaphthoquinone derivatives (5-7) were also synthesized with similar cytotoxicity as 1,2-pyranonaphthoquinones. In comparison to 1,2-naphthoquinones, six 1,4-naphthoquinones derivatives fused with pyran ring (8-10) and furan ring (11-13) were synthesized and they showed less cytotoxicity or inactive to the cancer cell lines. Moreover, compound 13 had significant cytotoxicity against HeLa cell line (IC(50) value of 9.25 microM) while it showed no toxic to vero cell.     

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant,Antibiotic, and Antifungal Activities

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH₄, the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by ¹H-NMR, ¹³C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC₅₀ values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC₅₀ values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol ( 4 d ) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol ( 7 d ) were determined to be 18.1 μg and 35.1 μg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.     

Patterns of polysaccharide biosynthesis in differentiating cells of maize root-tips

1. The patterns of incorporation of radioactivity from d-[6-(3)H]-, d-[1-(14)C]-, d-[U-(14)C]- and d-[6-(14)C]-glucose and [U-(14)C]myoinositol into the neutral sugars and uronic acids of the polysaccharides synthesized in different regions of the root-tip of maize were determined. 2. The root-cap tissue synthesized a slime in which a polysaccharide that contained a high proportion of fucose (32%) and galactose (21%) was found. This polysaccharide is synthesized only by the root-cap cells, and very little polysaccharide containing fucose is synthesized in adjacent tissues. Part of the meristematic tissue of the root is surrounded by the cap cells. A section of the root that contains both these tissues can be analysed, and the polysaccharide synthesized by the meristematic region can be obtained since the contribution of the root-cap cells can be found by the amount of fucose formed. 3. It was shown that there is very little difference in the polysaccharide synthesis of the meristematic region from that of the cells immediately behind it. In the more mature cells, however, the amount of xylose synthesized relative to that of arabinose is increased, and the proportion of xylose and arabinose formed in the matrix polysaccharides is increased whereas that of galactose is decreased. 4. The effect of 2,4-dichlorophenoxyacetic acid (2,4-D) on polysaccharide synthesis was to bring about a decrease in the relative amount of galactose synthesized in the matrix polysaccharides of cells immediately adjacent to the meristematic region and also in the more mature tissue. The growth factor also increased the amount of xylose synthesized relative to that of arabinose in the more mature tissue. These metabolic effects were related to a very obvious change in the morphological appearance of the root-tips. 5. Radioactivity from [U-(14)C]myoinositol was incorporated mainly into xylose, arabinose and galacturonic acid rather than into the hexoses, although small amounts of these sugars were formed.