A thesis submitted to the Faculty of Science,
University of the Witwatersrand,
Johannesburg
In fulfillment of the requirements for the Degree of Doctor of Philosophy
10th May 2013 / The syntheses of the naturally occurring naphthoquinone fungal metabolites
dehydroherbarin and anhydrofusarubin as well as the acetal core of marticin are
described in this thesis.
Starting from 2,4-dimethoxybenzaldehyde, dehydroherbarin was prepared in 11
steps in an overall yield of 4.5 %. The naphthalene segment of dehydroherbarin was
constructed and functionalized utilizing reactions including a Stobbe condensation,
O-allylation, and a Claisen rearrangement with the key step being a regioselective
phenyliodine bis(trifluoroacetate) mediated methanol addition to the naphthalene.
The pyran ring was assembled by a lithium aluminium reduction followed by Wackertype
oxidation reaction.
Two unnatural synthetic naphthoquinones, (3R,4R) 3-hydroxy-7,9-dimethoxy-3-
methly-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[g]isochromen-4-yl nitrate and 3,4-
dihydroxy-7,9-dimethoxy-3-methyl-3,4-dihydro-1H-benzo[g]isochromene-5,10-dione,
were also produced on route to accessing dehydroherbarin.
Anhydrofusarubin was synthesized from 2,4,5-trimethoxybenzaldehyde in 12 steps in
an overall yield of 5.3 % by employing the same synthetic methodology developed
towards the assembly of dehydroherbarin. To our knowledge, this represents the first
formal synthesis of anhydrofusarubin.
The assembly of model system of the 6,6-bicyclic pyran ring arrangement found in
the naturally occurring naphthoquinone marticin is also described. 11-
(hydroxymethyl)-9-methyl-10,13-dioxatricyclo[7.3.1.02,7]trideca-2(7),4-diene-3,6-
dione was produced racemically in 9 steps, starting from 2,5-dihydroxyacetophenone
in a 3.3 % overall yield, with the key reaction again being a Wacker-type oxidation
reaction
The related 6,7-bicyclic acetal compound, 3,6-dimethoxy-9-methyl-10,13-
dioxatricyclo[7.3.1.02,7]trideca-2,4,6-triene, was also made inadvertently in 7 steps,
from 2,5-dihydroxyacetophenone in a 6.5 % overall yield.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/13000 |
| Date | 06 August 2013 |
| Creators | Pillay, Adushan |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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