Chemo-, Regio- and Diastereoselective Synthesis of Azaspiro Tetra-/Pentacyclic Scaffolds with Anticancer Activity
1Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China.
Abstract:
We report an efficient and highly selective synthesis of azaspiro polycyclic scaffolds with excellent chemo-, regio-, and diastereoselectivities. This method exhibits broad substrate scope (44 examples), and the resulting tetracyclic compounds can be readily elaborated to complex pentacyclic lactams (8 examples). DFT calculations demonstrate thermodynamic control over the diastereoselectivity. Notably, the lead compound 7h exhibiting nanomolar cytotoxicity against PANC-1 cells (IC50 = 92 nM), underscoring the potential for generating natural product-like antitumor agents.
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