Synthetic applications of a three-component Mannich reaction. Total synthesis of IL-6 inhibitor (+)-madindoline A and B

A three-component Mannich reaction of 3a-hydroxyfuroindoline (3), β-ketoester and formaldehyde was employed as an efficient and concise method to synthesize naturally-occurring (+)-Madindolines A (1) and B (2). The scope and limitations of the Mannich reaction with 3 are described.