7431-95-0

The transient receptor potential vanilloid type-2 (TRPV2) protein is a nonselective Ca2+ permeable channel member of the TRPV subfamily, still considered an orphan TRP channel due to the scarcity of available selective and potent pharmacological tools and endogenous modulators. Here we describe the discovery of novel synthetic long-chain capsaicin derivatives as potent TRPV2 antagonists in comparison to the totally inactive capsaicin, the role of their hydrophobic chain, and how the structure-activity relationships of such derivatives led, through a ligand-based approach, to the identification of endogenous long-chain fatty acid ethanolamides or primary amides acting as TRPV2 antagonists. Both synthetic and endogenous antagonists exhibited differential inhibition against known TRPV2 agonists characterized by distinct kinetic profiles. These findings represent the first example of both synthetic and naturally occurring TRPV2 modulators with efficacy in the submicromolar/low-micromolar range, which will be useful for clarifying the physiopathological roles of this receptor, its regulation, and its targeting in pathological conditions.

Hydroxy fatty acid dehydrogenase, which is involved in polyunsaturated fatty acid saturation metabolism in Lactobacillus plantarum AKU 1009a, was cloned, expressed, purified, and characterized. The enzyme preferentially catalyzed NADH-dependent hydrogenation of oxo fatty acids over NAD+-dependent dehydrogenation of hydroxy fatty acids. In the dehydrogenation reaction, fatty acids with an internal hydroxy group such as 10-hydroxy-cis-12-octadecenoic acid, 12-hydroxy-cis-9-octadecenoic acid, and 13-hydroxy-cis-9-octadecenoic acid served as better substrates than those with α- or β-hydroxy groups such as 3-hydroxyoctadecanoic acid or 2-hydroxyeicosanoic acid. The apparent Km value for 10-hydroxy-cis-12-octadecenoic acid (HYA) was estimated to be 38 μM with a kcat of 7.6 × 10-3 s-1. The apparent Km value for 10-oxo-cis-12-octadecenoic acid (KetoA) was estimated to be 1.8 μM with a kcat of 5.7 × 10-1 s-1. In the hydrogenation reaction of KetoA, both (R)- and (S)-HYA were generated, indicating that the enzyme has low stereoselectivity. This is the first report of a dehydrogenase with a preference for fatty acids with an internal hydroxy group.

The present study focused on synthesizing bolaamphiphiles from the readily available and inexpensive castor oil, a vegetable oil, which contains about 90% of ricinoleic acid. Two classes of symmetric and asymmetric bolaamphiphiles with acetylcholine head groups were synthesized and characterized by spectroscopic analysis. These novel bolaamphiphilic compounds self-assemble in aqueous media to form stable cationic spherical nano-sized vesicles that are potential drug delivery systems.

(R)-Ricinoleic acid methyl ester obtained from commercial castor oil was transformed in a three-step procedure into its S-enantiomer in overall 36% yield using ionic liquid (1-butyl-3-methylimidazolium acetate) in the key step process. The developed procedure provides easy access to (S)-ricinoleic acid and its methyl ester of over 95% enantiomeric excess. Optical rotations of the newly obtained compounds as well as their chromatographic and spectral characteristics are provided and discussed in the context of enantiopurity both of the substrate material and the final products.

β-Ketoesters are valuable building blocks for the synthesis of compounds with different biological activities. In this study, a series of fatty β-ketoesters were obtained from fatty acids and Meldrum's acid using N,N-dicyclohexylcarbodiimide and dimethylaminopyridine. In addition, we demonstrate for the first time the synthesis of new fatty β-ketoesters from oleic (cis-C18:1), elaidic (trans-C18:1), ricinoleic (cis-C18:1, 12-OH), linoleic (cis,cis-C18:2), and linolenic (cis,cis,cis-C18:3) acids in good yields.

Methods and compositions for the production of oil, fuels, oleochemicals, and other compounds in recombinant microorganisms are provided, including oil-bearing microorganisms and methods of low cost cultivation of such microorganisms. Microalgal cells containing exogenous genes encoding, for example, a lipase, a sucrose transporter, a sucrose invertase, a fructokinase, a polysaccharide-degrading enzyme, a keto acyl-ACP synthase enzyme, a fatty acyl-ACP thioesterase, a fatty acyl-CoA/aldehyde reductase, a fatty acyl-CoA reductase, a fatty aldehyde reductase, a fatty acid hydroxylase, a desaturase enzyme, a fatty aldehyde decarbonylase, and/or an acyl carrier protein are useful in manufacturing transportation fuels such as renewable diesel, biodiesel, and renewable jet fuel, as well as oleochemicals such as functional fluids, surfactants, soaps and lubricants.

Copolyesters based on purified ricinoleic (RA) and lactic (LA) acids with different RA:LA ratios were synthesized by thermal polycondensation and by transesterification of high molecular weight poly(lactic acid) (PLA) with ricinoleic acid and repolyesterification. Thermal polycondensation resulted in random P(LA-RA) copolyesters of molecular weights between 2000 and 8000 with the polymers containing 20% or more RA were liquid at room temperature. Transesterification of high molecular weight PLA with pure ricinoleic acid and repolymerization of those oligomers by condensation resulted in multiblock P(PLA-RA) copolyesters of molecular weights between 6000 and 14000. Polymers containing 50% RA were liq uid at room temperature. 1H NMR spectroscopy analysis coupled with information from DSC allowed de ;ermination of the polymer structure. Polymers prepared by thermal polycondensation are random cope lymers (h > 1), while the copolymers prepared by transesterification have a multiblock character (h LA) decreased from 12 to 4 for the LA-RA 9:1 and 5:5 copolymers prepared by thermal polycondensation and from 50 to 17 for the corresponding LA-RA copolymers prepared by transesterification. Thermal analysis by DSC revealed crystalline structure for polyester synthesized by transesterification. For polyesters synthesized by random condensation on y P(LA-RA) 90:10 w/w contained crystalline domains.

The preparation of 2,3-diricinolein by lipase-catalyzed hydrolysis of triricinolein has been developed. Lipase-catalyzed hydrolysis of triricinolein provided (2R)-2,3-diricinolein in high diastereoselectivity.

Disclosed herein is a cosmetic care or makeup composition comprising a) at least one polyester resulting from esterification of at least one triglyceride of at least one hydroxylated carboxylic acid with at least one aliphatic monocarboxylic acid and with at least one aliphatic dicarboxylic acid, and b) at least one pasty compound. This composition makes it possible to obtain a deposition on a keratin materials which can be lubricious, glossy, and comfortable, can have sharply defined outlines, does not migrate, and whose color intensity can be enhanced and/or whose color retention after challenge can be enhanced.

Disclosed herein is a composition, for example, a cosmetic care and/or makeup composition for a keratin material, comprising, in a cosmetically acceptable medium, i) at least one polyester resulting from esterification of at least one triglyceride of at least one hydroxylated carboxylic acid with at least one aliphatic monocarboxylic acid and at least one aliphatic dicarboxylic acid, ii) at least one oil of a molar mass ranging from 650 to 10 000 g/mol, and iii) at least one colorant. The composition may possess cosmetic properties and can, for example, endow the makeup or care product with properties of gloss, smoothness of application and comfort. Further disclosed herein is the use of the at least one polyester and the at least one oil with a molar mass ranging from 650 to 10 000 g/mol in a physiologically acceptable composition as an agent for endowing the composition with properties of slip, gloss, comfort, definition, non-migration, enhanced color intensity and/or enhanced color retention after challenge.

Diricinoleylphosphatidylcholine (I) in an optically active form is obtained with good yields and a high purity by means of a process which comprises: a) esterifying the terminal carboxylic group of ricinoleic acid (III) with an alcohol having from 1 to 4 carbon atoms to give the corresponding ester having formula (IV); b) protecting the hydroxylic group of the ester of ricinoleic acid (IV) with a protecting group removable under bland operating conditions and isolating the ester of ricinoleic acid of which the hydroxylic group (V) is protected; c) hydrolyzing the ester of ricinoleic acid of which the hydroxylic group (V) is protected and isolating the ricinoleic acid of which the hydroxylic group (VI) is protected; d) acylating L-α-glycerophosphatidylcholine (II) with an imidazolic or triazolic derivative of the compound having formula (VI) and isolating the diricinoleylphosphatidylcholine of which the hydroxylic group (VII) is protected; e) removing the protecting group from the hydroxylic group of the compound having formula (VII); and finally f) recovering and purifying the compound having formula (I) by means of chromatography.

1,2-Diricinoleoyl- and 1-ricinoleoyl-2-oleoyl-sn-glycero-3-phosphocholine were synthesised with good yields. The synthesis started with the preparation of ricinoleic acid from castor oil. The choice of a suitable agent to protect the -OH group of ricinoleic acid was a key factor to afford the final products. Several protecting groups were assayed but only β-methoxyethoxymethyl chloride (MEMCl) and 2,2,2-trichloroethyl chloroformate (TRECCl) gave reasonable yields and good optical purities of the final products. The overall yields for 1,2-diricinoleoyl-sn-glycero-3-phosphocholine and 1-ricinoleoyl-2-oleoyl-sn-glycero-3-phosphocholine were 32.1% (with respect to ricinoleic acid methyl ester using TREC as protecting group) and 10.3% (with respect to 1-trityl-glycero-3-phosphocholine), respectively.

Diricinoleylphosphatidylcholine (I) in an optically active form is obtained with good yields and a high purity by means of a process which comprises: a) esterifying the terminal carboxylic group of ricinoleic acid (III) with an alcohol having from 1 to 4 carbon atoms to give the corresponding ester having formula (IV); b) protecting the hydroxylic group of the ester of ricinoleic acid (IV) with a protecting group removable under bland operating conditions and isolating the ester of ricinoleic acid of which the hydroxylic group (V) is protected; c) hydrolyzing the ester of ricinoleic acid of which the hydroxylic group (V) is protected and isolating the ricinoleic acid of which the hydroxylic group (VI) is protected; d) acylating L-α-glycerophosphatidylcholine (II) with an imidazolic or triazolic derivative of the compound having formula (VI) and isolating the diricinoleylphosphatidylcholine of which the hydroxylic group (VII) is protected; e) removing the protecting group from the hydroxylic group of the compound having formula (VII); and finally f) recovering and purifying the compound having formula (I) by means of chromatography.

An efficient chemoenzymatic synthesis of R-(+)-ricinoleic acid lactone and (±)-12-OH-stearic acid lactone using Boc2O mediated macrolactonisation is reported.

Diacylglycerophosphocholines containing (R)-3-, (R)-12-, (R)-17-hydroxy octadeca(e)noic acids and the corresponding racemates were synthesized and purified to homogeneity. The influence of the position of the hydroxy group on the monolayer packing properties of these fatty acids and their phosphatidylcholines was studied by Langmuir techniques and 1,2-di-[(R)-12-hydroxy-octadec-cis-9-enyl]-sn-glycero-3-phosphocholine displayed the largest lift-off area (330 A2/molecule). This result was in line with the thermotropic phase behavior of these phospholipids, as measured by differential scanning calorimetry (DSC): the gel- to liquid-crystalline phase transition temperature (T(m))passed through a minimum of -15.1°C for 1,2-di-[(R)-12-hydroxy-octadec-cis-9-enyl]-sn-glycero-3-phosphocholine.

Water or lipid soluble, pharmacologically active, antioxidant, anti-phospholipase compounds that are chemically defined. The compounds protect mammalian cells by inhibiting PLA2 and preventing oxidation. In particular, each compound has at least two fatty moieties and no active hydroxy group. The compound may also have at least one ionizable group, which may a carboxyl group, and each of the fatty moieties has from sixteen to twenty carbon atoms and at least one cis-unsaturated double bond.

The ethylaluminium dichloride induced Friedel-Crafts acylation of unsaturated carboxylic acids, for example 10-undecenoic acid (1a) and oleic acid (5a), and of the respective alcohols 1b and 5b with acyl chlorides and cyclic acyl anhydrides gave the corresponding long-chain β,γ-unsaturated ketones 3, 6/7, 11 and 13/14 with ω-carboxy and ω-hydroxy functions, respectively.The intramolecular cyclization of petroselinic acid chloride (17) yielded (E)-2-dodecylidenecyclohexanone (18).Catalytic hydrogenation gave the respective saturated ketones 4, 8/9, 12, 15/16 and 19.Key Words: Friedel-Crafts acylation / β,γ-Unsaturated keto carboxylic acids and alcohols

Hydrolysis of esters proceeded at room temperature under high pressure in the presence of iPr2NEt or N-methylmorpholine using CH3CN-H2O (60:1) as the solvent.This very mild procedure enables the smooth hydrolysis of biologically important compounds such as amino esters, aliphatic unsaturated fatty esters, and β-hydroxy esters; no racemization, no isomerization, and no side reactions take place.

A useful method for the synthesis of macrocyclic lactones using (ω-carboxyalkyl)sulfonium salts was developed.Base-catalyzed intramolecular cyclization of (ω-carboxyalkyl)diphenylsulfonium salts 2 gave simple macrocyclic lactones in high yields at high dilution conditions. (ω-Carboxyalkyl)alkylphenylsulfonium salts 8 afforded simple macrocyclic lactone 6a and alkyl carboxylates 9.The reactions of (ω-carboxyalkyl)dialkylsulfonium salts 10 gave only esters without lactonization product 6a.The cyclization of S-(ω-carboxyalkyl)thiolanium salts 3 and S-(ω-carboxyalkyl)-2-methylthiolanium salts 4 took place readily under similar conditions to afford sulfur-containing macrocyclic lactones 13 and 15, respectively, in good yields.To investigate the reaction mechanism, sulfonium salt 25, having an optically active carbon atom, was prepared.The intramolecular cyclization of 25 took place with an inversion of configuration at chiral carbon atom to give ricinelaidic acid lactone (26; optical purity 66percent).

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Ethylaluminum dichloride, which is a strong Lewis acid and a proton scavenger, catalyzes the ene reactions of aliphatic aldehydes with nonnucleophilic alkenes.Higher aldehydes give good yields of ene adducts with terminal alkenes.Formaldehyde gives good yields of adducts with electron-deficient alkenes.This reaction has been used for the synthesis of recifeiolide, ricinelaidic acid, and the insect pheromones (E,E)-8,10-dodecadienyl acetate and (E)-9,11-dodecadienyl acetate.

A neutral and relatively simple new method for effecting internal macrocyclic esterification of omega -hydroxycarboxylic acids, based on a tin 'template-driven' extrusion process, is discussed and its application to the synthesis (macrocyclization step) of the macrolide antibiotics zearalenone, ingramycin, and nodusmicin detailed. An efficient, formal total synthesis of pyrenophorin using this technique is also presented. Attempts to extend the methodology to include the macrocyclization of omega -bromo carboxylic acids or omega -mercapto carboxylic acids were unsuccessful. However, although beta - and omega -amino carboxylic acids preferentially gave way to polymer formation, 4-,5, and 6-amino carboxylic acids readily condensed to give the corresponding five-, six-, and seven-membered lactams in excellent yields. For example, in this way, the bridged lactam 1-azabicyclo- left bracket 3. 3. 1 right bracket nonan-2-one was prepared in 77% yield as compared to the previously reported yield of less than 2%.

A series of ω-halo fatty acids, the longest being 16-iodohexadecanoic acid, was prepared by oxidation of the corresponding ketones with m-chloroperbenzoic acid in boiling chloroform, followed by ring opening usually with hydrogen iodide in acetic acid at 100 deg C.Solutions of these acids in dimethylformamide (DMF) at concentrations of 5E-3 - 5E-2 M were treated with an equivalent amount of dry Cs2CO3.The solutions were stirred at 40 deg C overnight.Workup of the reaction mixture produced a mixture of (macro)cyclic lactone (macrolide) and its dimer (dilide).For the case of 16-iodohexanoic acid the lactone was isolated in 85percent yield.Yields for other large ring macrolides were also excellent.It was demonstrated that substitution by carboxylate on a secondary halide also goes well to afford the corresponding macrolide with no detectable amount of elimination.The effects of ring size, concentration, and solvent on the ring closure of the cesium carboxylates formed in situ were investigated.DMF is the best solvent of those investigated for the ring closure.Cesium carboxylates also undergo more readily ring closure and in far better yield than the carboxylates of lithium, sodium, potassium, rubidium, silver, thallium, magnesium, strontium, or barium.The S-lactone of ricinelaidic acid was prepared optically pure in 80percent yield from optically pure mesylate of R-ricinelaidic acid, which was treated with cesium carbonate in dry DMF.This demonstrates that the ring closure proceeds with the anticipated SN2 inversion at the hydroxyl-bearing carbon atom.With the same approach optically pure S-zearalenone was protected and subjected to ring opening, and the hydroxyl group was activated as mesylate.Some racemization was found to occur in the ring-opening step.On treatment of this material with dry cesium carbonate in DMF, the desired ring closure took place in 80percent yield to provide an excess of the protected R enantiomer of zearalenone.On the basis of these results, some speculations are made concerning the action of cesium in promoting ring closure to macrocyclic lactones.