Design And Synthesis Of Derivatives Of Glycosylated Norcantharidin

Cantharidin is a natural active component extracted from Mylabris phalerata Pall and Mylabris cichorii L of Family Meloidae, and is mainly used for cancer. Toxicity of Cantharidin can make essential damage to heart and kidney. Norcantharidin(NCTD), as a derivative of Cantharidin, can inhibit growth of cancer cell, greatly alleviate stimulation of Cantharidin to urinary system, uniquely increase level of leucocyte, and is used for primary carcinoma of the liver in clinic.Asialoglycoprotein receptor(ASGP-R), which is one of the best receptor-mediated hepatic targeting approaches, can deliver compounds with galactose residue to liver parenchymal cells. Conjugation of galactose with either pharmaceutical or polymer as a carrier effectively improve hepatic targeting efficiency.We used NCTD and amino acids to synthesize Cantharimides, carboxyl of which was connected with galactose through ethanolamine, and obtainβ-O-glycoside via participation of neighbouring group of acetyl.8 derivatives of NCTD were synthesized. We hope that modification of NCTD with a targeting group of galactose and linkers, may improve hepatic targeting efficiency, and achieve the aim to lower toxicity and enhance therapy effect.