The total synthesis of furanocembrane natural products

McAulay, Kirsten (2017) The total synthesis of furanocembrane natural products. PhD thesis, University of Glasgow.

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The furanocembranes are a family of marine diterpenoids isolated from octocoral invertebrates. These macrocyclic natural products possess interesting molecular structures including a furan ring at C3-C6 and a butenolide moiety encompassing C10-C12. As well as their unique structures, family members have shown promising biological activities, and thus they represent attractive synthetic targets.
This thesis describes the synthetic efforts towards two of these family members: pukalide and 7-acetylsinumaxmol B. In particular, focus has been directed towards the investigation of different synthetic strategies and the synthesis of key fragments; culminating in the total synthesis of 7-epi-pukalide and 7-acetylsinumaximol B. The key synthetic approach undertaken was designed to take advantage of new methodology developed by our group for the synthesis of highly functionalised furans, including epoxy-furans, in which tetrahydrothiophene (THT) was used as an organocatalyst. The reaction promotes the formation of both a furan and an epoxide in one step from a Knoevenagel condensation product.
In the first approach described herein, an intramolecular Knoevenagel condensation strategy for macrocycle formation was explored. The C12-C14/C1-C4 and C5-C11 were initially coupled through esterification; however, after further functionalisation, macrocyclisation could not be effected under Knovenagel conditions. The second approach focused on the use of an intermolecular Knoevenagel condensation reaction for fragment coupling. Although fragment coupling was successful further functionalisation proved to be difficult because of the reactive nature of the ynenone intermediates. The third and final approach investigated the development of a one-pot condensation and furan formation; combining the Knoevenagel condensation with organocatalytic tetrahydrothiophene to produce the furan directly from two separate fragments. This approach was successful, allowing completion of the full skeleton to be effected through macrolactonisation and ring-closing metathesis. Following this strategy both 7-epi-pukalide and 7-acetylsinumaximol B were accessed in 16 steps from the chiral pool starting material (R)-perillyl alcohol.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Total synthesis, natural product, furanocembrane.
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Supervisor's Name: Clark, Professor J. Stephen
Date of Award: 2017
Depositing User: Miss Kirsten McAulay
Unique ID: glathesis:2017-8448
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 02 Oct 2017 11:06
Last Modified: 19 Oct 2017 07:24
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