Formal synthesis of (+)-madindoline A, a potent IL-6 inhibitor, utilizing enzymatic discrimination of quaternary carbon.

Ken-ichi Shimizu, Mina Tomita, Ken-ichi Fuhshuku, Takeshi Sugai, Mitsuru Shoji

Department of Pharmaceutical Science, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

Natural product communications 2013 Jul

filter terms:

A formal synthesis of (+)-madindoline A was achieved. The Sunazuka's key intermediate, (4R,5S)-(-)-3-butyl-4-(tert-butyldimethylsiloxy)-5-methoxycarbonyl-2,5-dimethyl-2-cyclopentenone, was synthesized from easily available (2S,3S)-3-acetoxy-2-ethenyl-2-methylcyclopentanone. The starting material was reliably supplied by a chemo-enzymatic procedure in enantiomerically pure form. The synthesis was performed by straightforward transformations involving enone formation and regioselective introduction of the two alkyl side chains.

Citation

Ken-ichi Shimizu, Mina Tomita, Ken-ichi Fuhshuku, Takeshi Sugai, Mitsuru Shoji. Formal synthesis of (+)-madindoline A, a potent IL-6 inhibitor, utilizing enzymatic discrimination of quaternary carbon. Natural product communications. 2013 Jul;8(7):897-901