Synthetic Studies Toward Tetrodecamycin: An Efficient Approach to the Core Structure of the Antibiotic

Abstract An efficient synthetic pathway to the core structure 5 of the polyketide antibiotic tetrodecamycin (1A) has been developed. Our approach features the acid-catalyzed cyclization of a TERT-butyldimethylsilyl protected methyl α-(γ-hydroxyacyl) tetronate, leading to the novel tricyclic ring skeleton exhibited by 5. An insight into the mechanism of this key ring closure step has been gained. Furthermore an alternative pathway to this ring skeleton, based on a fluoride ion induced desilylation-cyclization sequence, has been disclosed.