Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors

Synthesis, Biological Evaluation, and Molecular Docking Study of 3-Amino and 3-Hydroxy-seco A Derivatives of α-Amyrin and 3-Epilupeol as Inhibitors of COX-2 Activity and NF-kB Activation

“…To the best of our knowledge, except for 2a and 2c , the synthesis of the seco -A-triterpene derivatives has not been reported. Also, this methodology proved to be efficient and shorter than others. ,,,, …”

“…Some strategies have been employed to obtain seco-triterpenes, including Beckmann fragmentation, 23,24,27,35 Schmidt reaction, 19 application of the taraxerane−oleanane rearrangement, 36 nucleophilic formylation and cyanation of conjugated enones, 30 and Baeyer−Villiger oxidation of the C-3 ketone. 22,25,26,28 Considering the importance of developing novel antiinflammatory agents, we explored the chemical modification in ring A of the anti-inflammatory natural triterpenes α-amyrin (1) and 3-epilupeol (2) by using the one-pot radical scission− oxidation process developed by Boto et al 37,38 So, treatment of α-amyrin 1 with (diacetoxyiodo)benzene (PhI(OAc) 2 ) and iodine (I 2 ) under irradiation with visible light at 26 °C afforded a separable mixture of 1a and 1b in 38% and 4% yield, respectively. The compounds 1a and 1b resulting from the scission− oxidation process are valuable precursors to other compounds by the transformation of the aldehyde group.…”

“…Also, this methodology proved to be efficient and shorter than others. 19,23,26,30,36 Anti-inflammatory Activity. Effect of the seco-Triterpenes on Nitric Oxide Production, Pro-inflammatory Cytokines (IL-6 and TNF-α) Secretion, and NF-κB Activation.…”

“…Because of the few chemical active sites within the rigid skeleton of pentacyclic triterpenes, the A-ring expansion and ring opening of the triterpenoid nucleus to produce a less rigid skeleton have been performed on lupane-, oleanane-, and ursane-type triterpenes. Some strategies have been employed to obtain seco -triterpenes, including Beckmann fragmentation, ,,, Schmidt reaction, application of the taraxerane–oleanane rearrangement, nucleophilic formylation and cyanation of conjugated enones, and Baeyer–Villiger oxidation of the C-3 ketone. ,,, …”

“…seco -A-Triterpenoids obtained as derivatives from natural pentacyclic triterpenes have shown various pharmacological activities including cytotoxic, − antiviral, − antimalarial, inhibitors of protein tyrosine phosphatase, and anti-inflammatory. , Anti-inflammatory seco -A-triterpenoids also are produced in higher plants, although only in small amounts, and have shown anti-inflammatory activity in both in vivo and in vitro studies. , The anti-inflammatory activity shown by seco -A-pentacyclic triterpenes has motivated some research groups to focus their interest on the synthesis of chemical derivatives that can enhance this pharmacological activity. , These studies have shown that pentacyclic triterpenes modified in ring A increase the anti-inflammatory potency to 10 000 times in comparison with the starting triterpene …”