The synthesis of caffeic acid esters, a new group of naturally occurring contact allergens

A Simple and Effective Method for Chemoselective Esterification of Phenolic Acids

“…[1 -5] In the presence of strong protic acids (Fisher esterification), phenolic acids could be esterified with good chemoselectivity, [6] but the harsh reaction conditions and the excess of alcohol made this strategy of limited applicability. The cesium salts of phenolic acids have been reported to react with alkyl halides in a highly chemoselective way, [2] but the yield is modest along with an excess of halides. Recently, Appentino et al reported the preparation of phenolic acid esters with good chemoselectivity by Mitsunobu reaction, [7] but the modest yields and costly reagents limited it for practical applications.…”

“…Phenolic acid esters motifs have been found in bioactive natural products, for example, the NF-k B inhibitors CAPE, [1] the honeybee propolis contact allergen prenyl caffeate, [2] and the EGCG mimic and HIV-1 reverse transcriptase inhibitor hydroxytyrosol gallate. [3] In many cases, phenolic acid esters are also used as important intermediates for the medicine synthesis.…”

Allergy to honeybee … not only stings

“…In 100% (six of six) and 70% (seven of 10) [21] of the patients a honey allergy was confirmed via serological sIgE antibodies and in 83% (five of six) the allergy was confirmed with skin tests [30 && ]. Honey does not contain the main allergic components in propolis such as caffeic acid esters [36] but cross-reactivities have been found between honey and bee venom [20]. In fact, nine of 22 and four of six of honey allergic patients were sensitized to honey bee venom [20].…”

Chemoselective Esterification of Phenolic Acids and Alcohols

“…Phenolic alcohol and phenolic acid ester motifs are widespread within bioactive natural products, with examples being, within primary esters, the NF-κB inhibitors CAPE ( 1a ) , and capsiate ( 2 ), the honeybee propolis contact allergen prenyl caffeate ( 1b ), and the EGCG mimic and HIV-1 reverse transcriptase inhibitor hydroxytyrosol gallate ( 3 ) . These compounds are structurally unsophisticated, but their reported syntheses are not easily amenable to the generation of analogues, due to either a heavy burden of protecting groups or the use of harsh conditions and/or a large excess of one of the reactants. − …”