Glycosyl esters of amino acids : Part IV. Synthesis of 1-O-(acylaminoacyl)-2,3,4,6-tetra-O-benzyl-D-glucopyranoses by the imidazole-promoted active ester and dicyclohexylcarbodiimide methods

1-O-(Acylaminoacyl)-2,3,4,6-tetra-O-benzyl-D-glucopyranoses were prepared in high yields by two routes involving direct participation of imidazole in the ester linkage formation; namely, (a) the accelerated active-ester method, and (b) the imidazole-promoted dicyclohexylcarbodiimide condensation. The compounds were synthesized from 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose and pentachlorophenyl esters of optically active benzyloxycarbonyl- and tert-butyloxycarbonyl-amino acids in method (a) or benzyloxycarbonyl- and acetyl-amino acids in method (b). By both methods, anomeric mixtures of D-glucosyl esters were obtained; they were resolved by column chromatography and the α and β anomers were fully characterized. The retention of configuration of the amino acid moiety was determined from optical rotations of acylamino acid methyl esters formed from D-glucosyl esters with methanolic sodium methoxide. With benzyloxycarbonyl and tert-butyloxycarbonyl protecting groups, a high degree of retention of optical activity was established in both methods-method (a) being slightly superior.     

Synthesis of 24(S)-hydroxycholesterol esters responsible for the induction of neuronal cell death

We synthesized several candidates of 24(S)-hydroxycholesterol (24S-OHC) esters, which are involved in neuronal cell death, through catalysis with acyl-CoA:cholesterol acyltransferase-1 (ACAT-1). We studied the regioselectivity of the acylation of the secondary alcohol at the 3- or 24-position of 24S-OHC. The appropriate saturated and unsaturated long-chain fatty acids were esterified with the protected 24S-OHC and then de-protected to afford the desired esters at a satisfactory yield. We then confirmed by HPLC monitoring that the retention times of four esters of 24S-OHC, namely 3-oleate, 3-linoleate, 3-arachidonoate and 3-docosahexaenoate, were consistent with those of 24S-OHC esters observed in 24S-OHC-treated SH-SY5Y cells.     

The composition of external lipids from adult whiteflies,Bemisia tabaci and Trialeurodes vaporariorum

The total surface lipids, including the wax particles, of the adult whiteflies of Bemisia tabaci and Trialeurodes vaporariorum were characterized. At eclosion, there were similar amounts of long-chain hydrocarbons, aldehydes, alcohols and wax esters. Within a few hours post-eclosion, long-chain aldehydes and long-chain alcohols were the dominant surface lipid components, C₃₄ on B. tabaci and C₃₂ on T. vaporariorum. Hydrocarbons, mainly n-alkanes, were minor components of the surface lipids. The major wax esters were C₄₆ on B. tabaci and C₄₂ on T. vaporariorum. The major acid and alcohol moieties in the wax esters of B. tabaci were C₂₀ and C₂₆, respectively, and of T. vaporariorum were C₂₀ and C₂₂, respectively. Both B. tabaci and T. vaporariorum had a minor wax ester composed of the fatty acid C_18:1 esterified to the major alcohols, C₃₄ and C₃₂, respectively. Bemisia were readily distinguished from Trialeurodes based on the composition of their wax particles and/or their wax esters; however, no differentiating surface lipid components were detected between biotypes A and B of B. tabaci.     

l-Carvyl Esters as Penetration Enhancers for the Transdermal Delivery of 5-Fluorouracil

To develop effective and safe penetration enhancers, a series of l-carvyl esters, namely, 5-isopropenyl-2-methylcyclohex-2-en-1-yl heptanoate (C-HEP), 5-isopropenyl-2- methylcyclohex-2-en-1-yl octanoate (C-OCT), 5-isopropenyl-2-methylcyclohex-2-en-1-yl decanoate (C-DEC), 5-isopropenyl-2-methylcyclohex-2-en-1-yl dodecanoate (C-DOD), 5-isopropenyl-2-methylcyclohex-2-en-1-yl tetradecanoate (C-TET), and 5-isopropenyl-2-methylcyclohex-2-en-1-yl palmitate (C-PAL), was synthesized from l-carveol and saturated fatty acids (C7–C16). The volatility of l-carveol and l-carvyl esters was evaluated by a live weight loss experiment. The enhancing effects of l-carvyl esters on 5-fluorouracil (FU) were investigated in the in vitro permeation experiment on rat skin. The stratum corneum (SC) uptakes of the enhancers were tested in vitro by gas chromatography. Only the l-carvyl esters with a moderate SC uptake, namely, C-OCT (C8), C-DEC (C10), and C-DOD (C12), showed a potential to enhance FU skin permeation. An evident parabolic relationship was found between the permeation enhancement of FU and the SC uptake of the l-carvyl esters. The l-carvyl esters with a chain length of C8–C12 seemed to be favorable for FU.     

Sex pheromone precursors in Spodoptera littoralis (Lepidoptera: Noctuidae)

Female pheromone gland extracts of Spodoptera littoralis were analyzed for pheromone precursors. Large amounts of fatty methyl esters were found and a positive relationship between the methyl esters and the pheromonal components was observed. The esters were identified on the basis of capillary gas chromatography, coupled gas chromatography with mass spectroscopy and dimethyl disulfide derivatization, and subsequent gas chromatography with mass spectrometry. The characteristic fatty esters of S. littoralis are methyl (Z)-9-tetradecenoate, (E)- and (Z)-11-tetradecenoate, (Z,E)-9,12-tetradecadienoate, (Z,E)-9,11-tetradecadienoate, and (Z)-11-hexadecenoate. The biosynthesis of the monosaturated acids involves probably the common E11 and Z11 desaturases and chain shortening. For the biosynthesis of the novel diene acids, we propose a second, specific desaturation of (Z)-9-tetradecenoate by an E11 desaturase to produce (Z,E)-9,11-tetradecadienoate or by an E12 desaturase to produce (Z,E)-9,12-tetradecadienoate.     

Butyldimethylsilyl ethers of iodine-catalysed solvolysis products of long-chain epoxides

Epoxides of methyl esters of elaidic and oleic acids were allowed to react with methanol, ethanol, n-propanol, iso-propanol and n-butanol, in the presence of iodine, to give the corresponding alkoxyhydroxy methyl esters. Ethyl elaidate epoxide gave a hydroxymethoxy methyl ester when treated with boron trifluoride in methanol but the ethyl ester group was not attacked with iodine as catalyst. Mass spectra of the alkoxyhydroxy esters contained strong peaks which demonstrated the location in the chain of the original epoxide ring. Iodine also catalysed the addition of water to methyl elaidate or oleate, giving erythro- and threo-9,10-dihydroxyoctadecanoates, respectively. The alkoxyhydroxy esters were quantitatively converted to t-butyldimethylsilyl ethers by reaction with t-butyldimethylchlorosilane/imidazole/dimethylformamide reagent at 100°C but the dihydroxyoctadecanoates were not completely derivatised. Mass spectra of all the t-butyldimethylsilyl ether derivatives contained intense fragments allowing the molecular weights and the positions of the ether functions to be easily determined.     

Synthesis of N-hydroxycinnamoyl amide derivatives and evaluation of their anti-oxidative and anti-tyrosinase activities

Twelve N-hydroxycinnamoyl amino acid amide ethyl esters (CAES) were synthesized by using l-amino acid ethyl ester hydrochloride and corresponding cinnamic acid (ferulic acid, acetylferulic acid and caffeic acid) as raw materials in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-hydrochloride (EDC) and 1-hydroxybenzotriene (HOBt). The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities of CAES were evaluated. The anti-tyrosinase activities of N-feruloyl amino acid ethyl esters and the hydroxyl (OH) free radical scavenging activities of N-caffeoyl amino acid ethyl esters were also examined. DPPH free radical scavenging activity was shown in all CAES, of which N-caffeoyl amino acid ethyl esters demonstrated higher radical scavenging activity than N-feruloyl amide derivatives, and (E) -N-(caffeic acid)-l-glycinate ethyl ester (c₅) had the strongest ability to scavenge free radicals with an IC₅₀ value of 18.6 µM. The acetylferuloyl amino acid esters exhibited the highest tyrosinase inhibition activity among the tested amides.     

Long chain esters of Virola species

The esters of n-fatty acids and ω-hydroxy n-fatty acids of β-sitosterol, D-glucose and ferulic acid (trans and cis) as well as β-sitosterol, fatty acids and β-sitosteryl-β-D-glucoside were isolated from three Virola species and identified by optical data and chemical reactions. A novel series of acidic esters derived from C₂₂C₂₉ ω-hydroxy fatty acids and cis- and trans-ferulic acid is reported for the first time. These compounds also occurred as the corresponding diester 1-monoglycerides whereas the ω-hydroxy acids themselves were also present as the corresponding glucosyl esters.     

Reduction by a model of NAD(P)H: XI. Stereochemistry of a lactate dehydrogenase-model reaction

Stereochemistry of the biomimetic reduction of α-keto esters with NAD(P)H-model compounds has been investigated. The model compound with the R-configuration reduces the α-keto esters to the (R)-α-hydroxy esters, whereas (S)-α-hydroxy esters are afforded by the reduction with the S-configurational model compounds. It has been concluded that pro-R and -S hydrogens of the model compounds with R- and S-configuration, respectively, contribute predominantly to the reduction.     

Fatty acid ethyl esters in the liverwort Conocephalum conicum

A series of fatty acid ethyl esters ranging from C₁₄ to C₂₄ was isolated from a hexane extract of the liverwort Conocephalum conicum, these esters accounted for 77% of the extract. The ethyl esters consisting of even-numbered fatty acids were predominant and ethyl palmitate was the major constituent.     

Wax composition of sargassum fulvellum

Sixty-seven compounds were characterized in the wax of Sargassum fulvellum. Characteristic components were the 5-methylhexyl esters of octanoic, decanoic, lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic and linolenic, and the 2-ethylhexyl esters of the same acids. The wax of S. fulvellum contains hydrocarbons (1.6%), esters (21.8%), free acids (74.9%) and free alcohols (0.3%). The principal free alcohols range in chain length only from C₆ to C₇.     

Daucane esters from Ferula communis subsp. communis

Fourteen daucane esters together with a known propiophenone 3,4-methylenedioxy-5-hydroxy-propiophenone, were isolated from Ferula communis subsp. communis. Except for the 6-(p-anisic acid) ester of jaeschkeanadiol all these esters are new. Structures were elucidated using spectral properties of the esters and their partial hydrolysis products. X-ray diffraction analysis of one of the compounds confirmed its structure including the stereochemical assignments made on the basis of spectral data.     

Formation of volatile alcohols and esters from aldehydes in strawberries

The aldehydes acetaldehyde, propanal, 2-methylpropanal, butanal, 3-methylbutanal, pentanal and hexanal, were reduced to their corresponding alcohols by incubation with strawberry fruit. The alcohols formed were then converted to their acetate, propionate, n-butyrate, isovalerate and n-caproate esters during the incubation with strawberry fruit. Simultaneous reaction of isobutyric acid, n-valeric acid and isocaproic acid with aldehyde and strawberry fruit resulted in the formation of esters of these acids. In all seven alcohols and 54 esters were produced by means of incubation of aldehydes and volatile fatty acids with strawberry fruit.     

Lipids of four species of freshwater dinoflagellates

The steroidal derivatives, fatty acid alkyl esters and triacylglycerols have been identified in two cultured dinoflagellates, Woloszynskia coronata and Ceratium furcoides, and natural populations of two species, Peridinium lomnickii and P. cinctum. Within each species, the same sterol moieties occurred in free and esterified forms, but the species differed in the proportion of 4α-methyl and desmethyl sterols. Both groups occurred in the two Peridinium species, whereas W. coronata contained only 4α-methylsterols and C. furcoides, uniquely among dinoflagellates analysed to date, contained only desmethylsterols, although these were analogues of 4α-methylsterols present in the other species. 4α-Methyl steroidal ketones were present in P. lomnickii and W. coronata; cholest-4-en-3-one and 5α-cholestan-3-one were detected in C. furcoides, but no steroidal ketones were detected in P. cinctum. Methyl and ethyl esters of fatty acids (C₁₂C₁₈) were detected in three species, in P. cinctum the ethyl esters were dominant, while phytyl esters occurred only in the Peridinium spp. The molecular composition of triacylglycerols containing only saturated and monoenoic acyl groups was determined by GC-MS. Lower carbon number constituents from W. coronata contained a C₄ acyl group, previously found only in animal milk fats.     

Degradation of phorbol esters by Pseudomonas aeruginosa PseA during solid-state fermentation of deoiled Jatropha curcas seed cake

Large amount of seed cake is generated as by-product during biodiesel production from Jatropha seeds. Presence of toxic phorbol esters restricts its utilization as livestock feed. Safe disposal or meaningful utilization of this major by-product necessitates the degradation of these phorbol esters. The present study describes the complete degradation of phorbol esters by Pseudomonas aeruginosa PseA strain during solid state fermentation (SSF) of deoiled Jatropha curcas seed cake. Phorbol esters were completely degraded in nine days under the optimized SSF conditions viz. deoiled cake 5.0 g; moistened with 5.0 ml distilled water; inoculum 1.5 ml of overnight grown P. aeruginosa; incubation at temperature 30 °C, pH 7.0 and RH 65%.SSF of deoiled cake seems a potentially viable approach towards the complete degradation of the toxic phorbol esters.     

Candida rugosa lipase mediated multigram synthesis of acid part of S(+)-atliprofen,a new NSAID and molecular modeling studies aimed at predicting selectivity of the enzyme

An efficient procedure to prepare S-4-(3-thienyl)phenyl-α-methylacetic acid, an intermediate of a recently approved non-steroidal anti-inflammatory cyclooxygenase inhibitor atliprofen by enantioselective hydrolysis of the corresponding esters in presence of candida rugosa lipase is reported. The methyl and butyl esters of the racemic acid 2 were synthesized and subjected to enantioselective hydrolysis by the lipase to give S-4-(3-thienyl)phenyl-α-methylacetic acid upto 97.86% ee. The observed enantioselectivity during the hydrolysis of the substrate by the lipase was rationalized by molecular modeling studies. The methyl esters of both R and S-enantiomers of 4-(3-thienyl)phenyl-α-methylacetic acid, naproxen and ketoprofen were taken for the modeling studies. The results of the modeling studies are in conformity with the experimental observations.     

Antimalarial activity of 10-alkyl/aryl esters and -aminoethylethers of artemisinin

A series of n-alkyl/aryl esters were synthesized and their in vitro antiplasmodial activity was measured alongside that of previously synthesized aminoethylethers of artemisinin ozonides against various strains of Plasmodium falciparum. The cytotoxicity against human cell lines was also assessed. The esters were synthesized in a one-step reaction by derivatization on carbon C-10 of dihydroartemisinin. Both classes were active against both the 3D7 and K1 strains of P. falciparum, with all compounds being significantly more potent than artemether against both strains. The majority of compounds possessed potency either comparable or more than artesunate with a high degree of selectivity towards the parasitic cells. The 10α-n-propyl 11 and 10α-benzyl 18 esters were the most potent of all synthesized ozonides, possessing a moderate (∼3-fold) and significant (22- and 12-fold, respectively) potency increases against the 3D7 and K1 strains, respectively, in comparison with artesunate.     

4-Methylumbelliferyl esters as fluorogenic substrates for proteases

4-Methylumbelliferyl esters of amino acid derivatives have been synthesized using the carbodiimide, disulphite and carbonate methods. Of these, the first was shown capable of preparing 2-naphthyl and 4-methylumbelliferyl esters of benzoylglycine, benzyloxycarbonyl glycine and benzyloxycarbonyl-citrulline but not of benzoyl-N^G-nitroarginine. 2-Naphthyl benzoyl-N^G-nitroargininate was prepared successfully using di(2-naphthyl)sulphite. Bis(4-methylumbelliferyl)sulphite could not be prepared but 4-methylumbelliferyl benzoyl-N^G-nitroargininate was obtained by the use of an equilibrium method using diphenyl sulphite in the presence of 4-methylumbelliferone. A new reagent, phenyl 4-methylumbelliferyl carbonate, was synthesized and used for the preparation of the 4-methylumbelliferyl esters of benzoylglycine, benzyloxycarbonylglycine and benzoyl-N^G-nitroarginine. The 4-methylumbelliferyl esters of benzyloxycarbonylglycine and benzyloxycarbonylcitrulline were shown to be good substrates for the assay of proteases, including chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4). Disadvantages of 4-methylumbelliferyl esters are discussed.     

Separating the isomers—Efficient synthesis of the N-hydroxysuccinimide esters of 5 and 6-carboxyfluorescein diacetate and 5 and 6-carboxyrhodamine B

Diacetate protection of 5 and 6-carboxyfluorescein followed by synthesis of the N-hydroxysuccinimide esters allowed ready separation of the two isomers on a multi-gram scale. The 5 and 6-carboxyrhodamine B N-hydroxysuccinimide esters were also readily synthesised and separated.     

Polar epicuticular lipids of Lycopersicon pennellii

Trichome exudates of Lycopersicon pennellii yielded nine 2,3,4-tri-O-acylglucose esters as α- and β-anomers from the polar fraction of the epicuticular lipid mixture. The esters were primarily derived from 2-methylpropanoic, 2-methylbutanoic, 3-methylbutanoic, 8-methylnonanoic and n-decanoic acids, together with trace quantities of 10-methylundecanoic and n-dodecanoic acids.