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The total synthesis of lactonamycin (1), a natural product isolated from a soil sample, by
Matsomoto and co-workers1 is currently under investigation. Lactonamycin (1)
possesses antimicrobal activity against Gram-Positive bacteria including MRSA and
VRE as well as appreciable levels of cytotoxicity against tumor cell lines.
A highly oxygenated fused perhydrofuran-furanone structural motif and a
naphtha[e]isoindole ring system make up the hexacylcic core of lactonamycin (1).
Adding to the structural complexity, a 2,3,6-trideoxy sugar unit is connected to the core
structure via a highly hindered tertiary glycosidic linkage.
Various strategies for glycosidation, using the known ABCD alcohol (±)-2 as a model for
the tertiary alcohol of lactonamycin (1) are discussed. Of these include, the use of
classical glycosidation approaches and more novel strategies that employ open chain
glycosyl donors.
In particular, the synthesis of glycoside 4 and subsequent investigations towards target
compound 5 are described.