Study On Structural Modification And Activity Of Forskolins

This thesis comprised two parts:one was about structural modification and activity of forskolins;50 compounds were prepared by various methods of separation and structural modification,and their structures were identified mainly by NMR;and the activation of AC was studied.The other was with regard to recent progress on chemical and pharmacological studies thereof.In the first chapter,50 derivatives were synthesized by Steglich esterification and traditional acyl chloride methods.The above compounds were preliminarily screened for the activation of AC,which exhibited the activity of 7-deacetylforskolin was the closest to that of FSK and the best agonist for activating AC among the 50 derivatives.The activity of other derivatives to AC was lower than that of FSK.Moreover,esterification at different hydroxyl sites(1,6,7 and 9)on forskolins would lead to the decrease of activity,therefore,the hydroxyl groups at 1,6,7 and 9 were very important for their activity;furthermore,the 11-carbonyl group was also the key group decreased obviously when reduced to the 11-hydroxyl groupIn the second chapter,recent progress on chemical and pharmacological aspects of forskolins was reviewed.FSK,ISOF and their analogues showed significant biological activities and remarkable pharmacological effects,which were worthy of further study for the sake of developing better preparations for clinical diseases.