Direct Total Syntheses of Frenolicin B and Kalafungin via Highly Regioselective Diels-Alder Reactions
Frenolicin B, an anticoccidial agent, has been synthesized in six steps from ketone 3. Racemic kalafungin, an antifungal agent, has been synthesized in five steps. The key step in both syntheses, a regioselective Diels-Alder reaction, proceeds with complete regiocontrol and in excellent yield. One rationale for the remarkable stereocontrol is that the lactone ring induces ring-puckering in the quinone subunit which, in consort with electrostatic repulsion, contributes to the regioselectivity.
Reprinted (adapted) with permission from Journal of Organic Chemistry 60 (1995): 1154, doi:10.1021/jo00110a017. Copyright 1995 American Chemical Society.