Synthesis of A/B Ring Analogs of Territrem B and Evaluation of Their Biological Activities

Two series of territrem B analogs, i.e., 5 – 10 , containing both the 2‐en‐1‐one‐A‐ring and the aromatic‐E‐ring pharmacophores were designed and synthesized from jujubogenin ( 4a ). The anti‐acetylcholinesterase (anti‐AChE), anti‐caspase‐3, and other biological activities of these territrem‐B analogs and their intermediates were assessed. Compound 9b, 22a , and 24f were shown to be weak inhibitors of AChE. None of the synthesized compounds exhibited significant inhibitory activity on caspase‐3. On the other hand, compounds 22e, 24a, 7b , and 8a showed mild cytotoxicity on cultured KB cells, with IC₅₀ values of 2.0, 3.5, 6.5, and 14 μM , respectively. In addition, compounds 23b and 5f were active against injury arising from oxygen‐glucose deprivation.