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Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized  l -ascorbic acid-amino acid-norcantharidin conjugates are determined by  1 HNMR,  13 CNMR and MS spectrum. The results showed that compounds  6e ,  6g ,  6j ,  6l ,  6m ,  6b ,  6e ,  6i , and  6n  showed high cytotoxicity to HepG2 and compounds  6b ,  6e-g ,  6l ,  6n ,  7b ,  7d ,  7h ,  7i ,  7n ,  8g ,  8i  exhibited high cytotoxicity to SW480; Meanwhile, besides  6b ,  6e ,  6g , and  6k , the other compounds showed less toxic to LO2 at a concentration of 50 μg/mg after 72 h. Compound  6g  can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages.

Synthesis of l -ascorbic acid-amino acid-norcantharidin conjugates and their biological activity evaluation in vitro