Photochemical expansion of the dihydrobenzofuran neolignan chemical space enables suppression of c-myc transcription in colorectal cancer.

Expanding the chemical space of dihydrobenzofuran neolignans remains a significant synthetic challenge, limiting their systematic biological evaluation and drug discovery. Here, we describe a photochemical strategy that enables the efficient synthesis of diverse dihydrobenzofuran neolignans. In addition, we constructed a valuable natural product-inspired library comprising neolignans and closely related derivatives. In particular, their potential role in the regulation of c-myc expression at the mRNA level has remained largely unexplored. The establishment of this neolignan library enabled screening for modulators of c-MYC expression, leading to the identification of compound 23b as an active cellular hit that suppresses the proliferation of colorectal cancer cells and reduces c-MYC expression. These findings establish a methodological framework for the discovery of inhibitors of c-MYC expression from natural products and underscore the therapeutic potential of targeting c-MYC in cancer treatment.