99353-00-1Relevant articles and documents
Short Chain (≤C4) Esterification Increases Bioavailability of Rosmarinic Acid and Its Potency to Inhibit Vascular Smooth Muscle Cell Proliferation
Bla?evi?, Tina,Reznicek, Gottfried,Ding, Limin,Yang, Gangqiang,Haiss, Patricia,Heiss, Elke H.,Dirsch, Verena M.,Liu, Rongxia
, (2021/02/12)
Rosmarinic acid is a natural phenolic acid and active compound found in many culinary plants, such as rosemary, mint, basil and perilla. Aiming to improve the pharmacokinetic profile of rosmarinic acid and its activity on vascular smooth muscle cell proliferation, we generated a series of rosmarinic acid esters with increasing alkyl chain length ranging from C1 to C12. UHPLC-MS/MS analysis of rat blood samples revealed the highest increase in bioavailability of rosmarinic acid, up to 10.52%, after oral administration of its butyl ester, compared to only 1.57% after rosmarinic acid had been administered in its original form. When added to vascular smooth muscle cells in vitro, all rosmarinic acid esters were taken up, remained esterified and inhibited vascular smooth muscle cell proliferation with IC50 values declining as the length of alkyl chains increased up to C4, with an IC50 of 2.84?μM for rosmarinic acid butyl ester, as evident in a resazurin assay. Vascular smooth muscle cells were arrested in the G0/G1 phase of the cell cycle and the retinoblastoma protein phosphorylation was blocked. Esterification with longer alkyl chains did not improve absorption and resulted in cytotoxicity in in vitro settings. In this study, we proved that esterification with proper length of alkyl chains (C1–C4) is a promising way to improve in vivo bioavailability of rosmarinic acid in rats and in vitro biological activity in rat vascular smooth muscle cells.
Explorations of caffeic acid derivatives: Total syntheses of rufescenolide, yunnaneic acids C and D, and studies toward yunnaneic acids A and B
Griffith, Daniel R.,Botta, Lorenzo,St. Denis, Tyler G.,Snyder, Scott A.
supporting information, p. 88 - 105 (2014/01/17)
Yunnaneic acids A-D, isolated from the roots of Salvia yunnanensis, are hexameric (A and B) and trimeric (C and D) assemblies of caffeic acid that feature an array of synthetically challenging and structurally interesting domains. In addition to being caffeic acid oligomers, yunnaneic acids A and B are formally dimeric and heterodimeric adducts of yunnaneic acids C and D. Herein we report the first total syntheses of yunnaneic acids C and D featuring the formation of their bicyclo[2.2.2]octene cores in a single step from simple precursors via an oxidative dearomatization/Diels-Alder cascade that may have biogenetic relevance. In addition, exploitation of the key intermediate resulting from this cascade reaction has enabled rapid access to the structurally related caffeic acid metabolite rufescenolide through an unexpected Lewis acid-mediated reduction. Finally, we report the results of extensive model studies toward forming the dimeric yunnaneic acids A and B. These explorations indicate that the innate reactivities of the monomeric fragments do not favor spontaneous formation of the desired dimeric linkages. Consequently, enzymatic involvement may be required for the biosynthesis of these more complex family members.
Synthesis, characterization and free radical scavenging properties of rosmarinic acid fatty esters
Lecomte, Jerome,Giraldo, Luis Javier Lopez,Laguerre, Mickael,Barea, Bruno,Villeneuve, Pierre
experimental part, p. 615 - 620 (2011/06/17)
The hydrophobation of rosmarinic acid with saturated aliphatic primary alcohols of various chain lengths (methanol to eicosanol) was achieved via an acid-catalyzed esterification in the presence of a highly acidic sulfonic resin. The resulting alkyl rosmarinates were isolated, characterized and their global free radical scavenging activity was determined by the 2,2-diphenyl-1-picrylhy- drazyl method in the stationary state. Only the dodecyl ester showed a stronger activity than rosmarinic acid.
