New methods for carbohydrate annulation.
thesisposted on 19.11.2015, 08:48 by Andrew Joseph. Wood
Chapter 1 describes the synthesis of a 1,4-dicarbonyl compound 1 which was constructed by a sequence involving opening of a protected glucose epoxide with allyl magnesium chloride, alkylation and Wacker oxidation; the 1,4-dicarbonyl compound 1 readily underwent cyclisation under basic conditions to produce the cyclopentaannulated sugar derivative 2. Treatment of the cyclopentaannulated sugar derivative with N-bromosuccinimide and subsequent treatment with activated zinc completed the fragmentation of 2 to furnish the cyclopentanes 3. Chapter 2 describes the reduction of 2 which furnished a mixture of allylic alcohols 4 in a ratio of 8:1 in favour of either isomer depending on the conditions and reagents employed. The application of a Stork silyl methylene radical cyclisation of the a-cyclopentaannulated derivative led to a 2:1 mixture of trans and cis fused tricyclic ring systems. Treatment of the allylic cyclopentaannulated derivative, however, led to a single cis-fused product 5. This is in contrast to previous examples which show a mixture of cis and trans-fused 6,5-ring systems. Chapter 3 describes the continuation of work in the Jenkins group directed towards the synthesis of taxanes from glucose. A model study was undertaken to show the viability of a stepwise diene synthesis utilising selenium chemistry. This succesful model study showed that an enone to diene conversion was possible. The application of this methodology to the C-ring synthon 6 produced 7, the most advanced intermediate to date, as a single isomer.