Synthetic Studies Towards The DEF Tricyclic Core Of The Daphniphyllum Alkaloids Daphniyunnine D

This thesis is mainly focused on the synthetic studies towards the DEF tricyclic core of daphniphyllum alkaloid daphniyunnine D. It consists of the following two parts:In Chapter1, a brief introduction to Daphniphyllum alkaloids including their separations, structures, biological activities, and some background on the biomimetic synthesis is given. Daphniphyllum alkaloids are a structurally diverse group of polycyclic natural products isolated from the evergreen plant genus Daphniphyllum. So far, more than250members have been isolated from this genus. Some of them showed moderate cytotoxic activity against tumor cells. The structural complexity and biological significance of these natural products have led to significant interest from the synthetic community. The biomimetic synthesis of these alkaloid as well as the synthetic studies of their core framework have been well documented so far.Chapter2covers our synthetic studies toward the DEF Tricyclic Core of Daphniyunnine D. Calyciphylline A-type alkaloids contain a fascinating polycyclic skeleton. Following the discovery of calyciphylline A,19calyciphylline A-type alkaloids have been isolated. Among them, daphniyunnine D showed cytotoxic activity against two tumor cell lines, P-388and A-549, with ICso values of3.0and0.60μM, respectively. In this chapter, the previous syntheses of the core structure of calyciphylline A-type alkaloids and daphniyunnine D are briefly reviewed. Then our synthetic studies on the synthesis of the DEF tricyclic of daphniyunnine D are described. Our synthetic campaign started from commercially available cyclopentanone. A series of operatins such as hydroxyl ptotection, acylation, alkylation, and deprotection led to the desired intermediate2-158. An array of conditions has been attempted for the pivotal intramolecular double aldol reaction; however, none of them was successful. Finally, HWE reaction of phosphonate2-169was attempted; however, intramolecular Micheal addition took place instead.