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Title: Synthesis of trisubstituted olefins by RCM using an O-Si-C tether : application to the total synthesis of dolabelide C
Author: Wittmann, Stephane
ISNI:       0000 0004 5371 7865
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2015
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Dolabelide C is a macrolide, part of the dolablide family, isolated in 1997 from the Japanese sea hare, Dolabella auricularia. Dolabelide C contains a polyhydroxylated macrocycle structure with eleven stereogenic centers and two trisubstituted olefins. It exhibits cytotoxicity against cervical cancer HeLa-S3 cells. Dolabelide C and the other members of the dolabelide family have been the object of several studies in several groups. The approach envisaged in the Prunet group towards the synthesis of dolabelide C consists in disconnecting the molecule into two fragments of similar lengths, the C1-15 and the C16-30 fragments. Previously within the group, both fragments had been successfully synthesised. However, new routes have been envisaged in order to improve these syntheses. For the synthesis of the C16-30 fragment, the fragment had been previously synthesised by cross metathesis, but this reaction led to an E/Z ratio to 4:1 at best. The new route consists in employing a temporary silicon-tethered ringclosing metathesis reaction in order to obtain a single isomer. This method was investigated on model substrates and was then employed for the synthesis of the C16-30 fragment of dolabelide C. Finally, the use of a new route for the synthesis of the C1-15 fragment is discussed. The C1-15 fragment had been synthesised previously using a Mukaiyama aldol as the key step. However, as the ketone is not present in the natural product, several steps were required in order to remove it. The use of a cross metathesis between two fragments was investigated for the synthesis of this fragment in a more concise manner.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry