A practical synthesis of amino limonin/deoxylimonin derivatives as effective mitigators against inflammation and nociception.

A practical synthetic route, consisting of 5 steps, has been developed and applied successfully for converting limonin/deoxylimonin into the corresponding amino derivatives I- 5a-I- 5e and II- 5a-II- 5e. Deoxylimonin analogs II- 5a and II- 5b bearing an open A ring structure underwent ring closure reaction by employing the Mitsunobu procedure to afford II- 6a and II- 6b. All of the 12 newly synthesized compounds were subjected to preliminary screening for evaluating their inflammation and nociception inhibition efficacy. The most promising compounds, I- 5b and II- 5d, were selected for further investigation by a carrageenan-induced mouse paw edema model, both of which displayed a dose-response dependent manner and demonstrated superior anti inflammation capacity to that of indomethacin in the first 2 hours.