The Total Synthesis of (-)-Lemonomycin

Lemonomycin (1), a member of the tetrahydroisoquinoline family of antitumor antibiotics that includes the saframycins, ecteinascidins, and quinocarcins was originally isolated in 1964 from a fermentation broth of Streptomyces candidus and was found to have potent antibiotic activity against Staphylococcus aureus and Bacillus subtilis.1 The structure of lemonomycin, however, was not eluci-dated until 2000,2 when researchers at Wyeth-Ayerst discovered its activity against a variety of antibiotic-resistant bacterial strains. In addition to the connectivity and relative stereochemistry of lemonomycin, the authors reported antibiotic activity against methicillin-resistant S. aureus and vancomycin-resistant Entero-coccus faecium, as well as cytotoxicity against a human colon tumor cell line (i.e., HCT 116). Lemonomycin is unique among the nearly 60 natural products and hundreds of synthetic analogues in this family in that it bears a glycoside at C(18).3 This is especiall