Total Syntheses of (-)-Aspergilazine A and Dendridine A

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dc.contributor.advisor Sperry, J en
dc.contributor.advisor Brimble, M en
dc.contributor.author Boyd, Emily en
dc.date.accessioned 2015-10-30T02:57:35Z en
dc.date.issued 2015 en
dc.identifier.citation 2015 en
dc.identifier.uri http://hdl.handle.net/2292/27354 en
dc.description.abstract This thesis describes the first total synthesis of the bisindole alkaloids (-)-aspergilazine A and dendridine A. The total synthesis of (-)-aspergilazine A (1) began with the construction of (-)-brevianamide F (2) by the base-mediated deprotection-cyclisation of the dipeptide 65. 6-Bromobrevianamide F (54) was prepared in analogous fashion, with the required L-6- bromotryptophan obtained from the enzymatic resolution of the corresponding racemate 98. After a series of model and optimisation studies, it was found that the palladium-catalysed Narylation of (-)-brevianamide F (2) with the N-Boc-protected derivative of 6-bromobrevianamide (107) gave the dimer 108, which upon deprotection gave (-)- aspergilazine A. The ligand XPhos displayed a unique capability to efficiently carry out this N-arylation while simultaneously suppressing epimerisation of the sensitive C9 stereocentres. (-)-Aspergilazine A could be accessed directly by the N-arylation of (-)-2 with (-)-54 by a selective palladiumcatalysed N-arylation in the presence of three other possible arylation sites. The low yield in this step is due to the thermal instability of 54. This total synthesis confirmed the gross structure and absolute configuration of (-)-aspergilazine A. The first total synthesis of dendridine A (115) has been achieved using a biomimetic approach. The monomeric tryptamine 141 (hemi-dendridine A acetate) was obtained from the Fischer reaction between phenylhydrazine 183 and enamide 157 followed by deprotection. Subjecting 141 to several radical based oxidants in the hope of effecting a biomimetic parapara coupling revealed that tert-butyl peroxide was capable of effecting dimerisation, but unfortunately giving the undesired 6,6ʹ-dimer 187 resulting from an ortho-ortho coupling. This regiochemical outcome was favourably switched by employing the 7- isopropoxytryptamine 184 in a Scholl type-coupling using MoCl5/TiCl4, giving the 4,4ʹ-dimer as the major product, alongside a mixture of unidentifiable unsymmetrical dimers in a 2.9:1 ratio. Deisopropylation and acetamide hydrolysis gave a synthetic sample of dendridine A (115), which was spectroscopically identical to the natural product (compared as their diTFA salts). en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA99264819612602091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/nz/ en
dc.title Total Syntheses of (-)-Aspergilazine A and Dendridine A en
dc.type Thesis en
thesis.degree.discipline Chemical Sciences en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.rights.holder Copyright: The Author en
pubs.elements-id 502827 en
pubs.org-id Human Resources en
pubs.org-id Health and Safety en
pubs.record-created-at-source-date 2015-10-30 en


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