Synthetic Studies on Quassinoids: Total Synthesis and Biological Evaluation of (+)-Des-D-chaparrinone

A total synthesis of des-D-chaparrinone (2), which lacks the ring D delta-lactone of (-)-chaparrinone (1) has been developed. The synthesis commences with the known, readily available tricyclic ketone 3 (R = Me). Elaboration of the configuration at C(5) followed by resolution of 6 employing 2(R),3(R)-2,3-butanediol gave rise to 9. Installation of the ring C functionality provided 15 which was transformed into tricyclic diketone 25. Introduction of the ring A functional groups afforded 29, which upon exposure to aluminum trichloride and sodium iodide gave rise directly to (+)-des-D-chaparrinone (2). Biological studies revealed that (+)-2 was devoid of any solid tumor activity.