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Description:
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Apoptolidin 1 .1 was isolated in 1997 by Hayakawa and co -workers from a soil
bacterium Nocardiopsis sp . during screening for specific apoptosis inducers . The
primary biological test revealed that this polyketide macrolide induced apoptosis in cells
transformed with the adenovirus type E1A oncognene , but not normal cells . This
dissertation describes the latest studies in understanding of apoptolidin’s biological
activity mechanism and previous contributions towards its total synthesis . Synthesizing
apoptolidinone 1 .26 by an intra -molecular Horner -Wadsworth -Emmons approach
featuring a Suzuki coupling , cross metathesis and two diastereoselective aldol reactions is
discussed . 15 mg apoptolidinone is prepared via our previously developed intramolecular
Suzuking coupling approach .
Ammocidin 3 .1 , which was found to induce apoptosis in Ba /F3 -v12 cells in an IL -
3 free medium , is a specific apoptosis inducer discovered by Hayakawa and co -workers
in 2001 from Saccharothrix sp . AJ9571 . A strategy featuring Suzuki coupling , cross
metathesis , Yamaguchi macrolactonization and three asymmetric aldol reactions was
applied to the total synthesis of ammocidinone 3 .6 , the aglycone of ammocidin . The
preparation of the key building blocks was discussed in the following chapter : aldehyde
3 .8 (C14 -C19 ) was synthesized via Sharpless asymmetric epoxidation ; ethyl ketone 3 .9’ (C20 -C28 ) was prepared via Kobayashi and Crimmins’s asymmetric aldol
methodologies ; aldehyde 3 .14 (C7 -C13 ) was generated by Brown crotylation and cross
metathesis . |