4046-02-0Relevant articles and documents
Identification of 8-O-4/8-5(Cyclic)- and 8-8(Cyclic)/5-5-Coupled Dehydrotriferulic Acids, Naturally Occurring in Cell Walls of Mono- and Dicotyledonous Plants
Waterstraat, Martin,Bunzel, Diana,Bunzel, Mirko
, p. 7244 - 7250 (2016)
Besides ferulate dimers, higher oligomers of ferulic acid such as trimers and tetramers were previously demonstrated to occur in plant cell walls. This paper reports the identification of two new triferulic acids. 8-O-4/8-5(cyclic)-triferulic acid was synthesized from ethyl ferulate under oxidative conditions using copper(II)-tetramethylethylenediamine [CuCl(OH)-TMEDA] as a catalyst, whereas 8-8(cyclic)/5-5-triferulic acid was isolated (preparative size exclusion chromatography, reversed-phase HPLC) from saponified insoluble maize fiber. Structures of both trimers were unambiguously elucidated by high-resolution LC-ToF-MS/MS and one- (1H) and two-dimensional (HSQC, HMBC, COSY, NOESY) NMR spectroscopy. The newly described trimers were identified by LC-MS/MS in alkaline hydrolysates of insoluble fibers from maize, wheat, and sugar beet, indicating that ferulic acid cross-links between cell wall polymers are more diverse than previously recognized. Saponification experiments also suggest that the newly identified 8-O-4/8-5(cyclic)-triferulic acid is the naturally occurring precursor of the previously identified 8-O-4/8-5(noncyclic)-triferulic acid in plant cell walls.
Production of feruloylated lysophospholipids via a one-step enzymatic interesterification
Rychlicka, Magdalena,Maciejewska, Gabriela,Niezgoda, Natalia,Gliszczyńska, Anna
, (2020)
Incorporation of ferulic acid (FA) into egg-yolk phosphatidylcholine (PC) in a lipase-catalyzed acidolysis and interesterification process was studied using four commercially available immobilized lipases as catalysts and two acyl donors: ferulic acid (FA) and ethyl ferulate (EF). Novozym 435 and a binary solvent system of toluene/chloroform 9:1 (v/v) were found to be the most suitable biocatalyst and medium, respectively, and significantly increased the incorporation of FA into the phospholipid fraction. Subsequently response surface methodology (RSM) and Box-Behnken design were employed to evaluate the effects of substrate molar ratio, enzyme loading and time of the reaction on the process of interesterification. The selected optimized parameters were established as PC/EF molar ratio 1/15, enzyme load 30% (w/w) and incubation time 6 days. The process of interesterification at the optimized parameters carried out on a large scale afforded feruloylated lysophosphatidylcholine (FLPC) in high isolated yield of 62% (w/w).
Rapid syntheses of dehydrodiferulates via biomimetic radical coupling reactions of ethyl ferulate
Lu, Fachuang,Wei, Liping,Azarpira, Ali,Ralph, John
, p. 8272 - 8277 (2012)
Dehydrodimerization of ferulates in grass cell walls provides a pathway toward cross-linking polysaccharide chains limiting the digestibility of carbohydrates by ruminant bacteria and in general affecting the utilization of grass as a renewable bioresource. Analysis of dehydrodiferulates (henceforth termed diferulates) in plant cell walls is useful in the evaluation of the quality of dairy forages as animal feeds. Therefore, there has been considerable demand for quantities of diferulates as standards for such analyses. Described here are syntheses of diferulates from ethyl ferulate via biomimetic radical coupling reactions using the copper(II)-tetramethylethylenediamine [CuCl(OH)-TMEDA] complex as oxidant or catalyst. Although CuCl(OH)-TMEDA oxidation of ethyl ferulate in acetonitrile produced mixtures composed of 8-O-4-, 8-5-, 8-8- (cyclic and noncyclic), and 5-5-coupled diferulates, a catalyzed oxidation using CuCl(OH)-TMEDA as catalyst and oxygen as an oxidant resulted in better overall yields of such diferulates. Flash chromatographic fractionation allowed isolation of 8-8- and 5-5-coupled diferulates. 8-5-Diferulate coeluted with 8-O-4-diferulate but was separated from it via crystallization; the 8-O-4 diferulate left in the mother solution was isolated by rechromatography following a simple tetrabutylammonium fluoride treatment that converted 8-5-diferulate to another useful diferulate, 8-5-(noncyclic) diferulate. Therefore, six of the nine (5-5, 8-O-4, 8-5-c, 8-5-nc, 8-5-dc, 8-8-c, 8-8-nc, 8-8-THF, 4-O-5) diferulic acids that have to date been found in the alkaline hydrolysates of plant cell walls can be readily synthesized by the CuCl(OH)-TMEDA catalyzed aerobic oxidative coupling reaction and subsequent saponification described here.
Peroxidase-catalyzed oligomerization of ferulic acid esters
Bunzel, Mirko,Heuermann, Birgit,Kim, Hoon,Ralph, John
, p. 10368 - 10375 (2008)
Valuable information about possible types of linkages, reaction mechanisms, and sequences for oxidative coupling of phenolic compounds in planta is available from in vitro model systems. Ferulate oligomers were generated in a system using ethyl ferulate, peroxidase, and hydrogen peroxide under various conditions. A molar ferulate/H2O2 ratio of 1:1, an ethanol level of 30% in an aqueous sodium phosphate buffer (pH 6.0), and a reaction time of 10 min were considered to be ideal to produce maximal proportions of ferulate trimers and tetramers from ethyl ferulate as starting material. The dominant trimer and tetramer were each isolated from the reaction mixture and identified as 8-O-4/8-5(cyclic)-dehydrotriferulic acid triethyl ester and 8-5(cyclic)/4-O-5/8-5(cyclic)-dehydrotetraferulic acid tetraethyl ester. The structure of the 8-O-4/8-5(cyclic)-dehydrotriferulic acid triethyl ester revealed that a third ferulate unit is bound to a preformed 8-O-4-diferulate dimer, a surprising reaction sequence considering the dominance of 8-5-coupled dimers among dehydrodiferulates in H2O2/peroxidase-based model reactions. As 4-O-5-coupling is not favored in the dimerization process of ferulates, the main tetramer isolated in this study is probably formed by 4-O-5-coupling of two preformed 8-5(cyclic)-diferulates, a logical step in analogy with reactions occurring in lignin biosynthesis.
First stereoselective and concise synthesis of rhoiptelol C
Purushotham Reddy, Sudina,Chinnababu, Baggu,Venkateswarlu, Yenamandra
, p. 999 - 1003 (2014)
The first concise stereoselective total synthesis of diarylheptanoid rhoiptelol C (1) was achieved from readily available vanillin. The synthesis involves Keck's asymmetric allylation, olefin cross metathesis, and Sharpless asymmetric dihydroxylation reaction as key steps. Copyright
Lipase-catalyzed preparation of mono- and diesters of ferulic acid
Sandoval, Georgina,Quintana, Paula G.,Baldessari, Alicia,Ballesteros, Antonio O.,Plou, Francisco J.
, p. 89 - 97 (2015)
Lipophilic and stable derivatives of ferulic acid are required to improve its efficacy in fatty foods and to optimize its use in cosmetic and pharmaceutical preparations. We report an improved synthesis of ferulic acid monoesters (ethyl ferulate and lauryl ferulate) using immobilized lipase from Candida antarctica B (CALB) in diisopropyl ether (DIPE). Maximum yields were 89% and 85% in 200 h for ethyl and lauryl ferulate, respectively. Ethyl ferulate was further acylated with vinyl esters to form ferulate diesters. 4-Acetoxy-ethyl ferulate was obtained with the immobilized lipase from Alcaligenes sp. (QLG) with 59% yield in 72 h, whereas 4-dodecanoyloxy-ethyl ferulate (a new compound) was synthesized with 52% yield in 72 h using CALB. DIPE was the best solvent for the transesterifications. Finally, the anti-inflammatory activity of the synthesized derivatives was evaluated in vitro; the compounds bearing a dodecyl chain showed improved anti-inflammatory activity compared with short-chain esters.
Ruthenium-catalyzed intramolecular arene C(sp2)-H amidation for synthesis of 3,4-dihydroquinolin-2(1 H)-ones
Au, Chi-Ming,Ling, Cho-Hon,Sun, Wenlong,Yu, Wing-Yiu
supporting information, p. 3310 - 3314 (2021/05/29)
We report the [Ru(p-cymene)(l-proline)Cl] ([Ru1])-catalyzed cyclization of 1,4,2-dioxazol-5-ones to form dihydroquinoline-2-ones in excellent yields with excellent regioselectivity via a formal intramolecular arene C(sp2)-H amidation. The reactions of the 2- and 4-substituted aryl dioxazolones proceeds initially through spirolactamization via electrophilic amidation at the arene site, which is para or ortho to the substituent. A Hammett correlation study showed that the spirolactamization is likely to occur by electrophilic nitrenoid attack at the arene, which is characterized by a negative ρ value of -0.73.
Solvent role in the lipase-catalysed esterification of cinnamic acid and derivatives. Optimisation of the biotransformation conditions
Suárez-Escobedo, Laura,Gotor-Fernández, Vicente
, (2021/02/05)
The esterification of cinnamic acid has been deeply investigated using ethanol as nucleophile and Candida antarctica lipase type B (CAL-B) as suitable biocatalyst. Special attention has been paid to the role that the solvent plays in the production of ethyl cinnamate. Therefore, volatile organic solvents and deep eutectic mixtures were employed in order to find optimal reaction conditions. Once that hexane was selected as the solvent of choice, other parameters that affect the enzyme activity were investigated in order to produce ethyl cinnamate with excellent yield. The CAL-B loading, nucleophile equivalents, temperature and reaction time have been identified as key parameters in the enzyme efficiency, and the potential of lipase-catalysed esterification has been finally exploited to produce a series of ethyl esters with different pattern substitutions on the aromatic ring.
First total syntheses of four natural bioactive glucosides
Xu, Guangya,Wu, Min,Yao, Zhongquan,Lou, Hongbin,Du, Weihong,Song, Mingwei,He, Yujiao,Dong, Hongbo
supporting information, p. 1266 - 1271 (2021/02/06)
The efficient total syntheses of four biologically interesting natural glucosides Ethylconiferin, Butylconiferin, 2’-Butoxyethylconiferin and Balajaponin B, have been achieved for the first time starting from commercially available Vanilline via concise reaction sequence of 8–10 steps with the overall yield of 26–41%. This work definitely laid the foundation for the further pharmacological study of this kind of natural compounds. Meanwhile, currently developed approach could be used as a general synthetic strategy for the syntheses of other monolignol glucosides and their derivatives, and provides an opportunity for further study of the structure-activity relationship of this kind of glucosides.
Structural Fine-Tuning of Desmuramylpeptide NOD2 Agonists Defines Their in Vivo Adjuvant Activity
Guzelj, Samo,Nabergoj, Sanja,Gobec, Martina,Pajk, Stane,Klan?i?, Veronika,Slütter, Bram,Frkanec, Ru?a,?timac, Adela,?ket, Primo?,Plavec, Janez,Mlinari?-Ra??an, Irena,Jakopin, ?iga
supporting information, p. 7809 - 7838 (2021/06/28)
We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68, a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75, which shows superior adjuvant activity in vivo. Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.
