(+)-Pleuromutilin Synthetic Studies. Degradative and de Novo Acquisition of a Levorotatory Tricyclic Lactone Subunit

Article abstract of DOI:10.1021/jo00242a019

The diterpene antibiotics pleuromutilin and tiamulin have been degraded to the common levorotatory lactone 3 in four steps.This important intermediate has been constructed in optically active condition from simple starting materials.The key elements of this synthesis were (i) stereoselective introduction of the second methyl group in 8 regiospecific cyclopentenone annulation of this oxocyclohexanecarboxylate ester, (ii) stereocontrolled attachment of the lactone ring to give 20, and (iii) proper introduction of the methyl and vinyl substituens α to the lactone carbonyl functionality in 20.This and other synthetic methodologies have been utilized to prepare stereoisomers of 3 that could potentially lead to unnatural pleuromutilins by reconstruction of the cyclooctane ring.