First Total Synthesis of Bauerine C

Abstract

The first total synthesis of Bauerine C, a unique indoloquinazoline alkoloid, has been achieved from readily available 2,3‐dichloroaniline. The key step is the Japp–Klingmann condensation between 2,3‐dichloroaniline and ethyl‐2‐acetyl‐5‐phthalimido pentanoate to get 3‐[(2,3‐dichlorophenyl)‐hydrozono]‐pipiridin‐2‐one, which cyclizes to 7,8‐dichloro‐2,3,4,9‐tetrahydro‐β‐carbolin‐1‐one, which can be methylated by dimethyl sulphate to give 7,8‐dichloro‐9‐methyl 2,3,4,9‐tetrahydro‐β‐carbolin‐1‐one. This N‐methyl derivative is then subjected to dehydrogenation with 2,3‐dichloro‐5,6‐dicayano‐1,4‐benzoquinone (DDQ) to give the target compound Bauerine C.

Keywords:

• Bauerine C
• cyclization
• indoloquinazoline alkaloid
• Japp–Klingmann condensation
• methylation

Acknowledgment

The authors thank Dr. Reddy's Laboratories, Ltd., for supporting this work and Abhijit Mukherjee and Vilas Dahanukar of Custom Pharmaceutical Services for their constant help and encouragement. Cooperation extended by colleagues from the analytical division is gratefully acknowledged.