Direct oxa-Pictet-Spengler cyclization to the natural (3a,5)-trans-stereochemistry in the syntheses of (+)-7-deoxyfrenolicin B and (+)-7-deoxykalafungin.
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.
Eid
Clark N
CN
Chemical & Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. eidc@wyeth.com
Shim
Jaechul
J
Bikker
Jack
J
Lin
Melissa
M
D003500:Cyclization; D008968:Molecular Conformation; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C534896:7-deoxyfrenolicin B; C534897:7-deoxykalafungin; D009285:Naphthoquinones