Direct Oxa-Pictet−Spengler Cyclization to the Natural (3a,5)-<i>trans</i>-Stereochemistry in the Syntheses of (+)-7-Deoxyfrenolicin B and (+)-7-Deoxykalafungin

Abstract

The pyranonaphthoquinones (+)-7-deoxyfrenolicin B and (+)-7-deoxykalafungin were synthesized in four steps using an oxa-Pictet-Spengler cyclization that directly provided the natural (3a,5)-trans-substituted dihydronaphthopyrans with high diastereoselectivity. This outcome is in contrast to the unnatural (3a,5)-cis-substituted dihydronaphthopyrans reported under similar conditions for the syntheses of (+)-frenolicin B and (+)-kalafungin. Computational modeling is presented that provides insight into this unusual stereoselectivity.