Highly potent activity of isopulegol-derived substituted octahydro-2 H -chromen-4-ols against influenza A and B viruses

Acid‐modified Halloysite Nanotubes as a Stereoselective Catalyst for Synthesis of 2H‐Chromene Derivatives by the Reaction of Isopulegol with Aldehydes

“…Thus, 4 R ‐diastereomer obtained by the reaction of I with thiophene‐2‐carbaldehyde on K‐10 clay exhibited in vivo prolonged analgesic effect surpassing that of Diclofenac . 4 R ‐isomers synthesized with 5‐bromo‐thiophene‐2‐carbaldehyde or acetone displayed a profound anti‐influenza activity, whereas only poor antiviral effect was showed by 4 S ‐diastereomers ,. Quite recently we have demonstrated that an increase in selectivity to thiophenyl‐substituted chromenol with illite clay as a catalyst was observed with an increase in the initial concentrations of reactants, the catalyst to reactants ratio, and a decrease in the reaction temperature .…”

“…Some synthesized octahydro‐2 H ‐chromen‐4‐ols on the basis of isopulegol display a pronounced physiological activity . Thus, 4 R ‐diastereomer obtained by the reaction of I with thiophene‐2‐carbaldehyde on K‐10 clay exhibited in vivo prolonged analgesic effect surpassing that of Diclofenac .…”

“…Kinetic modeling was applied to rationalize the observed regularities . Considering high physiological activity of 4 R ‐diastereomers of octahydro‐2 H ‐chromenols, development of novel stereoselective catalysts for their synthesis is a very important task. Note that the use of triflates for synthesis of physiologically active chromenols has several drawbacks including their toxicity, complexity of separation, and high costs.…”

“…It is known that compounds with a chromene (benzopyran) scaffold have a broad spectrum of biological activity . A high pharmaceutical potential and low toxicity of these substances resulted in a considerable interest in the synthesis of new chromene derivatives . Recently, it has been shown, that in catalytic condensation of a natural allyl alcohol (−)‐isopulegol (I) with aldehydes, substituted octahydro‐2 H ‐chromen‐4‐ol (III) as 4 R ‐ and 4 S ‐diastereomers was formed along with a dehydration product IV (Scheme ).…”

“…Recently, it has been shown, that in catalytic condensation of a natural allyl alcohol (−)‐isopulegol (I) with aldehydes, substituted octahydro‐2 H ‐chromen‐4‐ol (III) as 4 R ‐ and 4 S ‐diastereomers was formed along with a dehydration product IV (Scheme ). Different catalysts such as I 2 , p ‐toluenesulfonic acid, BF 3 ⋅Et 2 O, zeolites, clays were used in this reaction . A relatively high 4 R /4 S ratio (9.0) with overall yields of 70–88 % were observed in condensation of isopulegol (obtained by cyclization of R ‐citronellal) with aromatic aldehydes at −78 °C using scandium triflate .…”