The synthesis of the quinones dehydroherbarin, anhydrofusarubin and the acetal core of marticin

Abstract

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.