Synthesis of etoposide lactam via a mitsunobu reaction sequence

A novel chemical sequence for the conversion of a lactone antitumor agent 1 (etoposide) to the corresponding lactam 2 is described. The key steps involve a Mitsunobu cyclization (Ph 3 P, DEAD) of the -hydroxymethyl acyl benzaldehyde hydrazone 6 to a lactam derivative 7 followed by reductive cleavage (RaNi) to lactam 2 .