Strychnos alkaloids: total synthesis, characterization, DFT investigations, and molecular docking with AChE, BuChE, and HSA

Abstract

An efficient five steps, the protection-deprotection synthetic a novel synthetic routes to(±) noruleine (±)-uleine, are reported starting from tetrahydrocarbazole fused monoalkyl nitrile at C-2 position that is prepared on multigram scale from 2-(3-ethyl-1-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)acetonitrile (1) as well as the key azocino[4,3-b]indole skeleton is constructed via the tetrafluoro-1,4-benzoquinone (TFB)-mediated cyclization of a tetrahydrocarbazole derivative possessing direct amide synthesis from nitrile. As a result, Total synthesis of noruleine and uleine has been developed, which is accomplished in 4 and 5- steps synthesis of the ABCD tetracyclic of the strychnos alkaloids with an overall yield of 44% and 39%, respectively. The DFT computations were performed with B3LYP/6-311g(d,p) level to determine inter and intramolecular interactions and reactivity features of the compound 3–6. Also, TD-DFT computations were performed to characterize the electronic absorption spectra of all compounds. Last, the interactions of compounds 3–6 with selected targets AChE, BuChE, and HSA were evaluated in light of the molecular dockings. The bioactivity and drug-likeness scores revealed that compound 6 3–6 can be proper candidate for future drug-design studies more than the other compounds.

Keywords

• Uleine
• Noruleine
• Alzheimer's disease
• DFT computations
• Molecular dockings