UC San Diego
Progress towards the total synthesis of the hasubanan alkaloids and acutumine
- Author(s): Nguyen, Thong Xuan
- et al.
Acutumine, a chlorine containing natural product has recently been rediscovered to inhibit T-cell growth, and aid in memory by enhancing memorisation and anti-amnesic properties in mice and rats. These studies reveal the promising benefits of acutumine in alleviating conditions that are related to loss of memory such as Alzheimer's, Parkinson's and Pick's disease. We have developed a synthetic strategy that allows access to the common \[220.127.116.11\] propellane core structure, including 2,3- dimethoxycyclohexenone and N-methylpyrrolidine moieties, among the hasubanan alkaloids featuring a facile conversion of a sterically hindered amide to ester via N- acylbenzotriazole and a Dieckmann cyclization of cis-fused bicycle to install the propellane framework. It is envisioned that a strategy towards the common propellane core skeleton found in the hasubanan alkaloids can be applied towards the synthesis of acutumine. Progress towards the total synthesis of acutumine is reported, featuring photo\[2+2\]cycloaddition reactions to install spiro\[5.5\]ring stereoselectively.