1234-09-9Relevant academic research and scientific papers
Expeditious and sustainable two-step synthesis of sinapoyl-l-malate and analogues: Towards non-endocrine disruptive bio-based and water-soluble bioactive compounds
Peyrot, Cédric,Mention, Matthieu M.,Fournier, Robin,Brunissen, Fanny,Couvreur, Julien,Balaguer, Patrick,Allais, Florent
supporting information, p. 6510 - 6518 (2020/11/09)
Faced with the increasing demand from both the cosmetic industries and consumers for bio-based, safe and natural skin products, sinapoyl-l-malate, widely described for its UV protection in plants, appears to be an excellent alternative to substitute chemical filters in sunscreens. Unfortunately, the only synthetic routes described in the literature were not only tedious but also exhibit a strong negative environmental impact, thus seriously limiting the industrialization and commercialization of sinapoyl-l-malate. Herein, a shorter and greener synthetic pathway involving Meldrum's acid opening with unprotected naturally occurring hydroxy acids and its subsequent Knoevenagel-Doebner condensation with biomass-derived p-hydroxybenzaldehydes was designed and developed. This two-step procedure, whom sustainability has been assessed using green metrics (atom economy (AE), process atom economy (PAE), E-factor and LCA), is a great alternative to the already reported procedures and allows the access to sinapoyl-l-malate and several analogs in average to good yield. The study of the anti-UV properties, stability against UV radiation, radical scavenging and antimicrobial activities of the targets revealed attractive properties as photostable UV filters, antioxidants and preservatives. Moreover, the water solubility brought by the free carboxylic acids facilitates the incorporation of these molecules in cosmetic formulations. Finally, their innocuousness toward endocrine disruption was demonstrated.
Design, synthesis, and biological evaluation of novel hybrid dicaffeoyltartaric/diketo acid and tetrazole-substituted l -chicoric acid analogue inhibitors of human immunodeficiency virus type 1 integrase
Crosby, David C.,Lei, Xiangyang,Gibbs, Charles G.,McDougall, Brenda R.,Robinson, W. Edward,Reinecke, Manfred G.
experimental part, p. 8161 - 8175 (2011/02/23)
Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor l-chicoric acid (L-CA) were prepared. Their IC50 values for 3′-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/β-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3′-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3′-end processing, a phenomenon previously attributed to the β-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.
