1.Palladium-catalyzed gamma-selective and stereospecific allyl-aryl coupling between acyclic allylic esters and arylboronic acids.
Ohmiya H1, Makida Y, Li D, Tanabe M, Sawamura M. J Am Chem Soc. 2010 Jan 20;132(2):879-89. doi: 10.1021/ja9092264.
Reactions between acyclic (E)-allylic acetates and arylboronic acids in the presence of a palladium catalyst prepared from Pd(OAc)(2), phenanthroline (or bipyridine), and AgSbF(6) (1:1.2:1) proceeded with excellent gamma-selectivity to afford allyl-aryl coupling products with E-configuration. The reactions of alpha-chiral allylic acetates took place with excellent alpha-to-gamma chirality transfer with syn stereochemistry to give allylated arenes with a stereogenic center at the benzylic position. The reaction tolerated a broad range of functional groups in both the allylic acetates and the arylboronic acids. Furthermore, gamma-arylation of cinnamyl alcohol derivatives afforded gem-diarylalkane derivatives containing an unconjugated alkenic substituent. The synthetic utility of this method was demonstrated by its utilization in an efficient synthesis of (+)-sertraline, an antidepressant agent. The observed gamma-regioselectivity and E-1,3-syn stereochemistry were rationalized based on a Pd(II) mechanism involving transmetalation between a cationic mono(acyloxo)palladium(II) complex and arylboronic acid, and directed carbopalladation followed by syn-beta-acyloxy elimination.
2.Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel.
Rodrigues N1, Bennis K2, Vivier D1, Pereira V3, C Chatelain F4, Chapuy E3, Deokar H2, Busserolles J3, Lesage F4, Eschalier A5, Ducki S6. Eur J Med Chem. 2014 Mar 21;75:391-402. doi: 10.1016/j.ejmech.2014.01.049. Epub 2014 Jan 31.
The TWIK-related K(+) channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs. It has been reported that TREK-1 -/- mice were more sensitive than wild-type mice to painful stimuli, suggesting that activation of TREK-1 could result in pain inhibition. Here we report the synthesis of a series of substituted caffeate esters (12a-u) based on the hit compound CDC 2 (cinnamyl 3,4-dihydroxyl-α-cyanocinnamate). These analogs were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid induced-writhing assay) leading to the identification a series of novel molecules able to activate TREK-1 and displaying potent analgesic activity in vivo.
3.Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.
Theodosis-Nobelos P1, Kourti M1, Tziona P1, Kourounakis PN1, Rekka EA2. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5028-31. doi: 10.1016/j.bmcl.2015.10.036. Epub 2015 Oct 19.
Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders.
4.Production of Salicylic Acid Precursors Is a Major Function of Phenylalanine Ammonia-Lyase in the Resistance of Arabidopsis to Peronospora parasitica.
Mauch-Mani B1, Slusarenko AJ. Plant Cell. 1996 Feb;8(2):203-212.
Arabidopsis ecotype Columbia (Col-0) seedlings, transformed with a phenylalanine ammonia-lyase 1 promoter (PAL1)-[beta]-glucuronidase (GUS) reporter construct, were inoculated with virulent and avirulent isolates of Peronospora parasitica. The PAL1 promoter was constitutively active in the light in vascular tissue but was induced only in the vicinity of fungal structures in the incompatible interaction. A double-staining procedure was developed to distinguish between GUS activity and fungal structures. The PAL1 promoter was activated in cells undergoing lignification in the incompatible interaction in response to the pathogen. Pretreatment of the seedlings with 2-aminoindan-2-phosphonic acid (AIP), a highly specific PAL inhibitor, made the plants completely susceptible. Lignification was suppressed after AIP treatment, and surprisingly, pathogen-induced PAL1 promoter activity could not be detected. Treatment of the seedlings with 2-hydroxyphenylaminosulphinyl acetic acid (1,1-dimethyl ester) (OH-PAS), a cinnamyl alcohol dehydrogenase inhibitor specific for the lignification pathway, also caused a shift toward susceptibility, but the effect was not as pronounced as it was with AIP.