Plakortolide stereochemistry revisited: the checkered history of plakortolides e and I

The relative configuration of the plakortolide metabolite (4) isolated from a Madagascan Plakortis sp. and named (+)-plakortolide I is revised following reassignment of the ¹³C signals for C-7 and C-16, thereby establishing that the metabolite isolated was likely (+)-plakortolide E (3). We propose that the name "plakortolide I" should be retained for the plakortolide metabolite 5 first isolated by the Faulkner group; its enantiomer 4 can then be named ent-plakortolide I in line with the description of Barnych and Vatèle. The spectroscopic data for MPA esters prepared from synthetic samples of seco derivatives of plakortolide E (3) and ent-plakortolide I (4) were compared with those of MPA esters of seco derivatives from naturally isolated plakortolides L (1) and K (2) and of seco-plakortolide E (6a). Likewise, the spectroscopic data for MTPA esters derived from 3 and 4 were compared with data for the MTPA esters derived from 5. These various comparisons established that the sign of the specific rotation associated with the natural isolates is an unreliable indicator of absolute configuration and verify that the absolute configurations of plakortolides L (1), K (2), E (3), and I (5) are (3S, 4S, 6S), (3R, 4R, 6S), (3R, 4R, 6R), and (3S, 4S, 6R), respectively.