35683-15-9Relevant academic research and scientific papers
Enantioselective synthesis of 3-hydroxytetradecanoic acid and its methyl ester enantiomers as new antioxidants and enzyme inhibitors
Kuecuek, Hatice Baspinar,Yusufoglu, Ayse
, p. 1087 - 1091 (2013/07/26)
Optically pure R and S enantiomers of 3-hydroxytetradecanoic acid and its methyl esters were synthesised by porcine pancreas lipase catalysed hydrolysis of racemic methyl 3-hydroxytetradecanoate in aqueous medium, with the aim of determining their antioxidant, antielastase and antiurease activities. The effects of the weight ratio of substrate/lipase and the reaction time were investigated. Optimum reaction conditions were determined. The resolution reaction with porcine pancreas lipase afforded (R)-3-hydroxytetradecanoic acid, which is a component of bacterially important lipid A, with greater than 99 % ee in excellent enantiomeric ratio (>900) after 7 h incubation with a substrate/lipase weight ratio of 3:1 and 43 % conversion of the substrate. Methyl (S)-3-hydroxytetradecanoate, which is the unreacted enantiomer of the racemic substrate, could be recovered with 98 % ee after 7 h resolution with a substrate/lipase weight ratio of 1:1 and 60 % conversion. (R)-3- Hydroxytetradecanoic acid was converted to its ester and the S methyl ester to its acid. This biocatalytic enantioselective resolution in aqueous medium presents an environmentally friendly and green chemistry method for the synthesis of R and S enantiomers of 3-hydroxytetradecanoic acid and its methyl esters.
Chemical synthesis of a glycolipid library by a solid-phase strategy allows elucidation of the structural specificity of immunostimulation by rhamnolipids
Bauer, Joerg,Brandenburg, Klaus,Zaehringer, Ulrich,Rademann, Joerg
, p. 7116 - 7124 (2007/10/03)
The first synthesis of a glycolipid library by hydrophobically assisted switching phase (HASP) synthesis is described. HASP synthesis enables flexible switching between solution-phase steps and solid-supported reactions conducted with molecules attached to a hydrophobic silica support. A library of glycolipids derived from the lead compound 1 - a strongly immunostimulatory rhamnolipid - with variations in the carbohydrate part, the lipid components, and the stereochemistry of the 3-hydroxy fatty acids was designed and synthesized. The enantiose lective synthesis of the 3-hydroxy fatty acid building blocks was achieved by employing asymmetric hydrogenation of 3-oxo fatty acids. Glycolipids were prepared by this approach without any intermediary isolation steps, mostly in excellent yields. Final deprotection to the carboxylic acids was accomplished by enzymatic ester cleavage. All prepared rhamnolipids were tested for their immunostimulatory properties against human monocyte cells by assaying the secretion of the cytokine tumor necrosis factor α (TNFα) into the medium. The observed structure-activity relationships of rhamnolipids indicate a specific, recognition-based mode of action, with small structural variations in the rhamnolipids resulting in strong effects on the immunostimulatory activities of the rhamnolipids at low micromolar concentrations.
Synthesis and antifungal activity of rhodopeptin analogues. 2. Modification of the west amino acid moiety.
Nakayama,Kawato,Inagaki,Nakajima,Kitamura,Someya,Ohta
, p. 977 - 980 (2007/10/03)
Structure-activity relationships of the west amino acid modified analogues of rhodopeptins, novel antifungal tetrapeptide isolated from Rhodococcus species Mer-N1033, have been investigated. Among the analogues synthesized, 2,2-difluoro and 2-hydroxy deri
A practical enantioselective synthesis of (S)-3-hydroxytetradecanoic acid
Matsuyama, Keisuke,Ikunaka, Masaya
, p. 2945 - 2950 (2007/10/03)
(S)-3-Hydroxytetradecanoic acid 1 has been synthesized in an overall yield of 27% from (S)-epichlorohydrin 2 as follows: (1) regio and chemoselective epoxide opening of 2 with a Grignard reagent under the catalysis by Cu(I) followed by consecutive epoxide
Enzymatic preparation of (S)-3-hydroxytetradecanoic acid and synthesis of unnatural analogues of lipid A containing the (S)-acid
Liu, Wen-Chi,Oikawa, Masato,Fukase, Koichi,Suda, Yasuo,Winarno, Hendig,Mori, Saeko,Hashimoto, Masahito,Kusumoto, Shoichi
, p. 1441 - 1450 (2007/10/03)
Synthesis of unnatural analogues, that contain (S)-3-hydroxytetradecanoyl moieties in place of the corresponding natural (R)-isomers, of both lipid A and its biosynthetic precursor, designated precursor Ia or lipid IV(A), has been achieved through our recently developed procedure. (S)-3-Hydroxytetradecanoic acid was prepared from its racemate through the optical resolution by the use of a lipase and subsequent fractional recrystallization. The (S)-acyl analogue of lipid A exhibited slightly stronger interleukin-6 inducing activity than the corresponding natural lipid A, and the (S)-acyl analogue of the biosynthetic precursor was far more active than the natural precursor in inhibiting the induction of interleukin-6 by lipopolysaccharide.
Efficient asymmetric synthesis of (R)-3-hydroxy- and alkanoyloxytetradecanoic acids and method for the determination of enantiomeric purity
Keegan, David S.,Hagen, Steven R.,Johnson, David A.
, p. 3559 - 3564 (2007/10/03)
An efficient synthesis of the (R)-3-hydroxy- and alkanoyloxytetradecanoic acid components of bacterial lipid A has been achieved using a Ru(II)-Binap-catalyzed low-pressure hydrogenation in the key step. The enantiomeric purity of p-bromophenacyl ester intermediate 4 could be assessed directly by chiral HPLC - obviating separate derivatization steps and/or chiral NMR shift studies.
Synthesis of an analog of biosynthetic precursor la of lipid A by an improved method: A novel antagonist containing four (S)-3-hydroxy fatty acids
Fukase, Koichi,Liu, Wen-Chi,Suda, Yasuo,Oikawa, Masato,Wada, Akira,Mori, Saeko,Ulmer, Arthur J.,Rietschel, Ernst Th.,Kusumoto, Shoichi
, p. 7455 - 7458 (2007/10/02)
Synthesis of an analog of a biosynthetic precursor of lipid A containing four (S)-3-hydroxytetradecanoic acids was effected via an improved synthetic route to investigate the relationship between the bioactivity and the chirality of the 3-hydroxy fatty acid residues in lipid A. The S-analog inhibited endotoxin-induced interleukin-6 (IL-6) production from human peripheral whole blood cells more strongly than the natural-type biosynthetic precursor with (R)-hydroxy acids, a known antagonist of LPS-induced cytokine release in human peripheral blood mononuclear cells.
Syntesis, Conformational Analysis, and Stereoselective Reduction of 14-Membered Ring 3-Keto Lactones
Neeland, Edward G.,Ounsworth, James P.,Sims, Russel J.,Weiler, Larry
, p. 7383 - 7394 (2007/10/02)
The synthesis of 3-oxo-13-tetradecanolide (5) and its 2-methyl and 2,2-dimethyl derivatives 7 and 8 have been carried out.The keto carbonyls in 5, 7, and 8 have been reduced with varying degrees of stereoselectivity.The stereoselectivity of the reduction depends on the counterion with the borohydride reducing agent, but selectivities approaching 100percent have been achieved for 5 and 7.The structure of the reduced products were determined by X-ray crystallography and chemical correlation.Heavy reliance on the stereoselectivity in the Frater dianion alkylation was used.The solution conformation of the β-keto lactones was found to be based on A both from NMR studies and molecular mechanics calculations.However, we are not able to predict the observed stereoselectivity in the hydride reduction of the ketones using this conformation.Thus we suggest the reduction proceeds through conformation B' in which the two carbonyls are chelated to the counterion.The conformations of the resulting alcohols are more complex and have both inter- and intramolecular hydrogen bonding which control the conformations.The use of polar maps to illustrate similarities and differences in conformations is demonstrated.These conformations are used to rationalize the physical and chemical properties of the β-keto and β-hydroxy 14-membered lactones.
