Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis

Abstract

Four undescribed biflavonoid alkaloids, sinenbiflavones A–D, were isolated from Cephalotaxus sinensis using a MS/MS‐based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR‐ESI‐MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A–D are the first examples of amentoflavone‐type (C‐3’–C‐8’’) biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C‐6‐methylated amentoflavone‐type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS‐CoV‐2 3CLpro inhibitory activity with 43 % inhibition rate at 40 μM.