Enantiospecific and enantioselective approaches to the natural (16R,19R)- and the unnatural
(16S,19S)- THF core of the bioactive acetogenin annonacin are described which utilizes both a chiral
pool synthesis and enzymatic transformations. In the antipodal (2S,5S) THF series derived from D-
(+)-glucosamine, the semi-protected THF aldehyde synthon allows for two-directional synthetic
elaboration through a Henry reaction with a lipid-like nitroalkane. The resulting nitroalcohol having
the unnatural (2S,5S)-THF core was oxidized to the corresponding -nitroketone using a modified
Collins oxidation. The intermediate -nitroketone has potential for the preparation of the C15-C32 core and analogues
through subsequent removal of the nitro group and reduction of the carbonyl.
Keywords: Acetogenins, angiogenesis, THF’s, lipases, chiral pool, Henry reaction.
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