Large scale total synthesis of apoptolidinone and progress towards the total synthesis of ammocidin

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Title: Large scale total synthesis of apoptolidinone and progress towards the total synthesis of ammocidin
Author: Liu, Qingsong
Abstract: 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 .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1054
Date: 2009-05-15

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Large scale total synthesis of apoptolidinone and progress towards the total synthesis of ammocidin. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1054 .

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