Synthesis of Camptothecin Melantotransferrin (p97) Conjugate Through a Carbamate Bond

Abstract

Through its 20‐hydroxy group and a carbamate bond, 20(S)‐camptothecin (1) is chemically linked to melanotransferrin (p97). The key step to modify the steric hindered hydroxy group of camptothecin is achieved by using triphosgene/DMAP in DMF and immediately reacting with tert‐butyl 6‐aminohexanoate (8). The novel camptothecin conjugate 4 is a potential agent for chemotherapy of brain tumor.

Keywords:

• Camptothecin
• Melanotransferrin
• Brain tumor
• Blood–brain barrier
• Drug delivery
• Bioconjugate

Acknowledgments

The authors are grateful to Ms. Grace Laliberte, Dr. Pascale Tiger, Dr. Malcolm Kennard, and Dr. Gavin Arthur for help discussions and part of analytic work.