O-benzoyl Derivative Research Articles

Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by Modulating NGF Signaling in PC12 Cells.

Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous mechanical understanding. In this work, sarcodonin G was chosen as a lead compound to prepare a series of 19- O-benzoyl derivatives by semisynthesis and their neuritogenic activities were evaluated. 6 and 15 (10 μM) were investigated with opposite effects in PC12 cells. 6 exhibited a superior activity to sarcodonin G by promoting NGF-induced neurite outgrowth, while 15 showed an inhibitory effect. Supportingly, 6 and 15 (20 μM) significantly induced and suppressed neurite extension in primary cultured rat cortical neurons, respectively. In mechanism, the two derivatives were revealed to influence NGF-induced neurite outgrowth in PC12 cells through the regulation of PKC-dependent and -independent ERK/CREB signaling as well as the upstream TrkA receptor phosphorylation. Furthermore, a possible pattern of interaction among NGF, 6/15 and TrkA was presented using molecular simulations. It revealed that 6/15 may contribute to the stabilization of the NGF-TrkAd5 complex by establishing several hydrophobic and hydrogen-bond interactions with NGF and TrkA, respectively. Taken together, 6 and 15 modulate PKC-dependent and -independent ERK/CREB signaling pathways possibly by influencing the binding affinity of NGF to the receptor TrkA, and finally regulate neurite outgrowth in PC12 cells.

Synthesis, Characterization and Anticancer Activity of Novel 1, 3, 4- Oxadiazolyl- and Pyrazolylquinoxalines

Synthesis, Characterization and Anticancer Activity of Novel 1, 3, 4- Oxadiazolyl- and Pyrazolylquinoxalines Omaima O. M. Farahat, Kamal F. M. Atta Abstract Synthesis of 2-[3-(5-hydroxymethyl)-1-phenyl-1H-pyrazol-3-yl]-2-oxoquinoxalin-1-yl acetohydrazide (3) was accomplished by the reaction of 3-(5-acetoxymethyl-1- phenyl-1H-pyrazol-3-yl)-1,2-dihydroquinoxalin-2-one (1) with ethyl bromoacetate followed by treatment with hydrazine hydrate under reflux. The key starting material 3 was used for the preparation of the target oxadiazolylpyrazolyl- and dipyrazolylquinoxalines. Thus, the reaction of 3 with ethyl formate or acetic acid afforded the acyl carbohydrazide derivatives 4 and 5 respectively. Moreover, benzoylation of 3 with benzoyl chloride in pyridine yielded the N-,O-dibenzoyl derivative 6 which, upon boiling with acetic anhydride or dimethyl formamide gave the O-benzoyl derivative 11. Furthermore, treatment of 3 with formic acid or acetic acid in the presence of phosphoryl chloride yielded the respective oxadiazolylpyrazolylquinoxalines 9 or 10. O-Acetylation of 4 and 9 or 3, 5 and 8 give the corresponding 1,3,4-oxadiazolylpyrazolyl quinoxalines 7 or 8. Additionally, synthesis of [3-(5-hydroxymethyl)-1-phenyl-1H-pyrazol-3-yl]-1-[(5-mercapto-1,3,4- oxadiazol-2-yl)methyl]quinoxalin-2-one (12) was performed by refluxing the carbhydrazide 3 with carbon disulphide which upon acetylation afforded the O-,Sdiacetyl derivative 13. On the other hand, the dipyrazolylquinoxalines 14 and 16 were obtained upon heterocyclization of the hydrazide 3 with acetylacetone or ethyl acetoacetate respectively. Acetylation of 14 and 16 gave the monoacetyl derivatives 15 and 17, respectively. The structural investigation of the new compounds is based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against three cell lines HCT-116 (colon carcinoma), HEPG2 (liver carcinoma) and MCF-7 (breast carcinoma) revealed that they possess high anti-tumor activities. Full Text: PDF DOI: 10.15640/jcb.v2n2a7

Chemoselective Reaction of Benzoylisothiocyanates with Hydroxyl Group of Salicylamide: a New and Convenient Entry Into 2-Aryl-4H-benzo[e][1,3]oxazin-4-ones

The reactions of benzoylisothiocyanates with salicylamide in pyridine-xylene solution occurs chemoselectively at the hydroxyl group of the salicylamide to afford the corresponding O-benzoyl derivatives. The latter products, on prolonged heating in pyridine-xylene solution, undergo cyclodehydration to give 2-aryl-4H-benzo[e][1,3]oxazin-4-ones in good yields. These compounds could also be synthesized by a direct one-pot reaction of benzoylisothiocyanates with salicylamide by slow addition of benzoylisothiocyanates into a solution of salicylamide in xylene-pyridine solution under reflux. The products have been characterized on the basis of satisfactory analytical and spectral data.

4-acyloxy- and 4-acylaminophthalonitriles and phthalocyanines based thereon

Reactions of 4-hydroxy- and 4-aminophthalonitriles with substituted benzoyl chlorides gave the corresponding N- and O-benzoyl derivatives, and the latter were used to obtain copper and nickel phthalocyanine complexes. Effect of the substituents in the latter on their electronic absorption spectra was studied. The obtained complexes were found to undergo association in organic solvents.

Polyhydroxylated pyrrolidines: synthesis from d-fructose of new tri-orthogonally protected 2,5-dideoxy-2,5-iminohexitols

The readily available 3- O-benzyl-1,2- O-isopropylidene-β- d-fructopyranose ( 2) was transformed into its 5- O- ( 3) and 4- O-benzoyl ( 4) derivative. Compound 4 was straightforwardly transformed into 5-azido-4- O-benzoyl-3- O-benzyl-5-deoxy-1,2- O-isopropylidene-β- d-fructopyranose ( 7) via the corresponding 5-deoxy-5-iodo-α- l-sorbopyranose derivative 6. Cleavage of the acetonide in 7 to give 8, followed by regioselective 1-O-silylation to 9 and subsequent catalytic hydrogenation gave a mixture of (2 S,3 R,4 R,5 R)- ( 10) and (2 R,3 R,4 R,5 R)-4-benzoyloxy-3-benzyloxy-2′- O- tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine ( 12) that was resolved after chemoselective N-protection as their Cbz derivatives 11 and 1a, respectively. Stereochemistry of 11 and 1a could be determined after total deprotection of 11 to the well known DGDP ( 13). Compound 2 was similarly transformed into the tri-orthogonally protected DGDP derivative 18.

Acylating and Arylsulfonylating Ability of O‐Derivatives of Isatin 3‐Oximes.

O-Acyl and O-arylsulfonyl derivatives of isatin 3-oximes have been synthesized and their interaction with alcohols and amines has been investigated. It was established that none of the esters of 1-substituted isatin 3-oximes reacted with the indicated nucleophiles. 1-Unsubstituted O-aryl and O-arylsulfonyl derivatives react with amines as acylating agents even at room temperature, but O-acetyl derivatives only on heating. Acylamides or arylsulfamides respectively are formed in this way. O-Acyl derivatives do not react with alcohols at room temperature. Only O-benzoyl derivatives form ethyl benzoate on heating in ethanol. A comparative analysis of mass spectrometric data on the processes of acylation and arylsulfonylation is given.

Acylating and arylsulfonylating ability of O-derivatives of isatin 3-oximes

O-Acyl and O-arylsulfonyl derivatives of isatin 3-oximes have been synthesized and their interaction with alcohols and amines has been investigated. It was established that none of the esters of 1-substituted isatin 3-oximes reacted with the indicated nucleophiles. 1-Unsubstituted O-aryl and O-arylsulfonyl derivatives react with amines as acylating agents even at room temperature, but O-acetyl derivatives only on heating. Acylamides or arylsulfamides respectively are formed in this way. O-Acyl derivatives do not react with alcohols at room temperature. Only O-benzoyl derivatives form ethyl benzoate on heating in ethanol. A comparative analysis of mass spectrometric data on the processes of acylation and arylsulfonylation is given.

(−)-Daucic acid: Proof of d- lyxo configuration, synthesis of its d- ribo, d- xylo, l- arabino and l- lyxo analogs, and biosynthetic implications

The dimethyl esters of the 2,6-anhydro-3-deoxy-hept-2-enaric acids with d- xylo, d- lyxo, l- arabino, l- lyxo- and d- ribo-configuration were synthesized from d-galactose and d-mannose, respectively, and further characterized by their di- O-acetyl and di- O-benzoyl derivatives. Comparison of their physical data with those of Daucus carota derived products revealed (−)-daucic acid to have d- lyxo-configuration 46 rather than the previously assigned d- xylo stereochemistry 1. Dimethyl daucate 43 could be converted by acid-induced ring contraction and dehydration into naturally occurring (+)-osbeckic acid 47, thereby proving its ( S)-configuration. Configurational identity in the pyranoid rings of (−)-daucic acid and KDO, together with available biosynthetic evidence on chelidonic acid 4, a leaf closing factor, suggests a joint, KDO 8-P-based pathway for their biosynthesis in plants.

N‐Amination of Unsymmetrically Substituted Pyrimidines. Synthesis of Isomeric N‐Aminopyrimidones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Trishydroxamates and triscatecholates based on monosaccharides and myo-inositol as artificial siderophores.

New trishydroxamates and triscatecholates based on methyl alpha-D-glucopyranoside, methyl alpha-D-galactopyranoside, methyl alpha-D-ribopyranoside and methyl alpha-D-xylopyranoside as well as on 1,3,5-tri-O-benzyl-myo-inositol were synthesized. N-Methylsuccinohydroxamate, N-methylglutarohydroxamate and their O-benzoyl derivatives were used as hydroxamate moieties. 2,3-Dihydroxybenzoyl derivatives and acylated compounds as well as 2,3- and 3,4-dihydroxybenzylidenehydrazino derivatives, partly with spacer groups, were utilized as catecholate components. The siderophore activity of the prepared siderophore analogues was examined by a growth promotion assay with various Gram-negative bacteria and mycobacteria and by the CAS-assay. Some trishydroxamates and triscatecholates showed siderophore activity on Gram-negative bacteria and triscatecholates on mycobacteria. Iron complexes of the trishydroxamates act as siderophores for all types of iron transport mutants. The recognition and uptake specificity of these compounds was studied by E. coli siderophore receptor and iron transport mutants. Structure activity correlations are discussed.

N-Amination of unsymmetrically substituted pyrimidines. Synthesis of isomeric N-aminopyrimidones

N-Amination of 6-amino-2-methyl-4-pyrimidone with O-(mesitylenesulfonyl)hydroxylamine leads to the 3-amino derivative. The isomeric 1,6-diamino-2-methyl-4-pyrimidone was obtained by the N-amination of the O-benzoyl derivative of the initial pyrimidone and removal of the benzoyl protection.

Synthesis of furanose derivatives of 3-deoxy- d- erythro-2-hexulosonic acid and their 3-bromo and 3-deuterio analogs

Methanolysis of 2,4,6-tri- O-benzoyl-2,3-dibromo-3-deoxy- d-altrono-1,5-lactone gave methyl 3-bromo-3-deoxy-2,4,6-tri- O-benzoyl-α- d- ribo-hex-2-ulofuranosonate ( 3) and the anomeric mixture of the analogous 4,6-di- O-benzoyl derivative, having HO-2 free. Compound 3 was subjected to debromination with tributyltin hydride and tributyltin deuteride in the presence of 2,2′-azo-bisisobutyronitrile affording, respectively, the corresponding derivatives of 3-deoxy- d- erythro-2-hexulosonic acid and its 3-deuterio analog. The structure of the products and intermediates was established by spectroscopic methods and chemical transformations.

Synthesis and polymerization studies of formaldehyde oxime and its derivatives

Formaldehyde oxime and three O-alkyl derivatives were examined as potential imine monomers. Formaldehyde oxime spontaneously polymerized below 60 °C and did not polymerize above 60 °C (ceiling temperature), even in the presence of free-radical or cationic initiators. The O-benzoyl derivative was isolated as the cyclic trimer but could not be converted into the monomeric form. Formaldehyde O-benzyloxime was synthesized and isolated. Attempted homopolymerizations in the presence of free-radical initiators only led to oligomers, whereas with cationic initiators only cyclic trimer was obtained. Copolymerizations with appropriate vinyl monomers and free-radical and anionic initiators yielded only low molecular weight polymers. Cationic copolymerizations gave higher molecular weights and polymer yields, but the polymers containing appreciable amounts of imine function had very low molecular weights. We conclude that the polymerizability of imines is extremely sensitive to the substitution pattern: imines with only a substituent on nitrogen are unstable and readily polymerize, whereas imines with more substituents generally do not polymerize. Electron-withdrawing substituents are more favorable to polymerizability. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1866–1872, 2000

Stereospecific synthesis of unnatural β-L-enantiomers of 2-chloroadenine pentofuranonucleoside derivatives

2′,3′-Dideoxy- (1), 2′,3′-unsaturated- (2), 2′,3′-dideoxy-3′-fluoro- (3), 3′-azido-2′,3′-dideoxy- (4) and 2′-deoxy- (5) β-L-ribofuranonucleosides of 2-chloroadenine have been synthesised and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of 2,6-dichloropurine with a suitable peracylated L-xylo-furanose (6). Treatment of the resulting protected β-L-nucleoside with methanolic ammonia followed by appropriate chemical modifications gave the 2-chloro-9-(2-deoxy-β-L-threo-pentofuranosyl)adenine 11. Its 5′-O-benzoyl derivative 12 was then converted to nucleosides 1 and 2 via radical deoxygenation reaction or base-promoted β-elimination of the corresponding mesyl ester. Additionally, compounds 3–5 were obtained from 12 either by reaction with (diethylamino)sulfur trifluoride or via Mitsunobu reactions using diphenylphosphoryl azide or benzoic acid as incoming nucleophiles. The prepared compounds were tested for their activity against HIV and HBV viruses, but they did not show significant antiviral activity nor cytotoxicity.

Reductive cleavage of the positional isomers of benzoylated and methylated methyl α- d-mannopyranoside

The four O-benzoyl-tri- O-methyl positional isomers, the six di- O-benzoyl-di- O-methyl positional isomers, the four tri- O-benzoyl- O-methyl positional isomers, and the tetra- O-benzoyl derivative of methyl α- d-mannopyranoside were synthesized, characterized, and subjected to reductive cleavage in the presence of triethylsilane and trimethylsilyl trifluoromethanesulfonate. The reactions were monitored by 1H NMR spectroscopy in order to establish the rates of the reactions and the identities of the products so formed. The tetra- O-benzoyl derivative, all tri- O-benzoyl- O-methyl positional isomers, and the 2,4-di- O-benzoyl-3,6-di- O-methyl positional isomer were fully stable to reductive-cleavage conditions, but the other di- O-benzoyl-di- O-methyl positional isomers and all O-benzoyl-tri- O-methyl positional isomers were converted to their respective 1,5-anhydro- d-mannitol derivatives via reductive cleavage of their anomeric carbon-oxygen bonds. For the mono- O-benzoyl positional isomers, the rate of reductive cleavage decreased in the order 2-O- benzoyl > 6-O- benzoyl > 3-O- benzoyl ≌ 4-O- benzoyl . Moreover, all mono- O-benzoyl positional isomers were cleaved at a much faster rate than the di- O-benzoyl positional isomers. These results suggest that both anchimeric assistance and inductive effects of the ester groups contribute to the observed reaction rate. Based upon these results it is suggested that reductive cleavage of benzoylated polysaccharides might serve as a means to cleave selectively at branched residues.

A convenient access to β-glycosides of N-acetyllactosamine

Iodoacetoxylation of 3,6-di- O-acetyl-4- O-(2,3,4,6-tetra- O-acetyl-β- d-galactopyranosyl)-1,5-anhydro-2-deoxy- d- arabino-hex-1-enitol (hexa- O-acetyllactal) and the corresponding hexa- O-benzoyl derivative, gave the α-1,2- trans 1- O-acetyl-2-deoxy-2-iodo adducts with high stereoselectivity and good yields. These were treated with an excess of trimethylsilyl azide in the presence of trimethylsilyl trifluoromethanesulfonate affording the corresponding α-1,2- trans 2-deoxy-2-iodoglycosyl azides. In the presence of an alcohol, a Staudinger reaction at the anomeric azide ledin situ to an iminophosphorane which rearranged with elimination of iodine at C-2. The aziridine intermediate thus obtained reacted with a suitable alcohol to afford the corresponding lactosamine β-glycosides. The reaction occurred with double inversion of configuration at C-1 and C-2. Deprotection of the amine functionality and further transformation into the acetamido derivatives could be achieved without isolation of the intermediates. © 1997 Elsevier Science Ltd.

N-(Diphenylphosphinothioyl)hydroxylamine: preparation, characterisation and base-induced transposition of sulfur and oxygen atoms in its O-benzoyl derivative 1

N-(Diphenylphosphinothioyl)hydroxylamine 5 has been prepared from Ph2P(S)Cl using H2NOSiMe3 and has been converted into its O-benzoyl derivative Ph2P(S)NHOCOPh 6. The principal reaction of the derivative 6 with base (NaOMe or ButNH2) is rearrangement, transposition of sulfur and oxygen giving Ph2P(O)NHSCOPh 7; this then reacts further, forming the phosphinic amide Ph2P(O)NH2 together with PhCO2Me or PhCONHBut. The rearrangement probably involves intramolecular nucleophilic displacement of benzoate by the PS group of 6, forming an intermediate with P, N and S atoms in a three-membered ring.

Chromatographic and mass spectrometric analyses of 1-monomycoloyl glycerol fraction from Rhodococcus lentifragments as per- O-benzoyl derivatives

Per- O-benzoylation of the 1-monomycoloyl glycerol fraction from Rhodococcus lentifagmentus gave a product that was amenable to fractionation into saturated (F 0), monounsaturated (F 1) and diunsaturated (F 2) species by argentation thin-layer chromatography. These fractions exhibited R f-values of 0.54, 0.22 and 0.05, respectively. Mass spectral analyses showed that F 0, F 1 and F 2 corresponded to derivatized 1-monomycoloyl glycerols in which mycolic acids ranged from C 32:0 to C 46:0, C 34:1 to C 48:1 and C 38:2 to C 50:2, respectively. Reversed-phase high-performance liquid chromatography revealed that per- O-benzoyl 1-monomycoloyl glycerols were amenable to fractionation into the corresponding homologous components. Moreover, the major individual homologous components could be collected for further structural investigation by mass spectrometry. The most significant peaks on the mass spectrum that represented per- O-benzoyl 1-monomycoloyl glycerol were: (1) the molecular ion, M +; (2) the molecular ion minus benzoic acid, M +-122; (3) the molecular ion minus two units of benzoic acid, M +-244; and (4) the molecular ion minus 1-hydroxy-2,3-dibenzoyl glycerol and benzoic acid, M +-422. In addition, effluents emerging from the chromatographic column were detected at wavelength 230 nm that allowed quantification of the eluting compounds.

Synthesis of 2- and 4-nitrophenyl β-glycosides of β-(1 → 4)- d-xylo-oligosaccharides of dp 2–4

2- and 4-Nitrophenyl β- d-xylopyranosides ( 4 and 5) were transformed, via dibutyltin oxide-mediated acylation, into the corresponding 2,3-di- O-benzoyl derivatives 11 and 15. Xylobiose and xylotriose were easily isolated by charcoal column chromatography from a commercially available material and converted into the di- and trisaccharide methyl 1-thio-β-glycosides 36 and 37. The 2- and 4-nitrophenyl β-glycosides of the β-(1 → 4)- d-xylo-oligosaccharides of dp 2–4 were synthesized by N-iodosuccinimide-silver triflate-promoted condensation using 11 and 15 as the glycosyl acceptors and ethyl 1-thio-β- d-xylopyranoside triacetate 16, 36, and 37 as the glycosyl donors. Also described are an improved preparation of 4 and 5, and the synthesis of 1-naphthyl β- d-xylopyranoside, as well as an alternative approach to the 2- and 4-nitrophenyl β-xylobiosides.

Semi-empirical calculations of intramolecular acyl transfer in cis-enols of O-aroyl acetylacetones

Intramolecular acyl transfer was studied in eight aroyl derivatives of cis enols of acetylacetone using various semiempirical hamiltonians. The transition state geometry and activation energy for each derivative is reported. A reaction rate relative to that for the O-benzoyl derivative was calculated for each member in the series. The calculated relative rate constants were correlated to the substituent electronic constants, σ, and to experimental relative rate constants. Good correlations were obtained in both cases with the exceptions of the p-chloro and m-nitro aroyl groups. The rates of acyl transfer were enhanced by electron withdrawing aroyl groups. Calculations with the PM3 hamiltonians reproduced experimental trends better than using AM1.