The Theoretical Total Synthesis of an Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline

¹ School of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013, China
² College of Engineering, The Pennsylvania State University, State College, 16803, United States
³ Changjun High School, Changsha, 410002, China

^* Corresponding author. E-mail address: liuhao171018@gmail.com

ABSTRACT.

A series of crinane-type alkaloid ambelline derivatives were assessed for their potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which has been shown to be effective medicine for the treatment of Alzheimer’s disease. However, no enzyme modification has been reported total synthesis. In this work, two possible theoretical synthesis paths of Crinane-type alkaloid ambelline were discussed in this article. The major difficulty of the proposed synthesis was the synthesis of the quaternary carbon. One of the approaches emphasized on the reactions between cyclic and heterocyclic compounds and substrates on the intermediates to generate the quaternary carbon shown on the desired product. The other approach utilized series of amine reactions and Michael addition to create the precursor for the reactant in the Diels-Alder reaction and, therefore, the quaternary carbon, and finally, the desired natural product was obtained after a weak acid workup. The synthesis of ambelline has the potential to provide new pathways for treatment of Alzheimer’s disease.