| Abstract
| - Two total syntheses of the unsymmetrical bis-indolylquinone natural product demethylasterriquinone B1 (also known as L-783,281) have been accomplished. The first exploits a known base-promoted condensation of indoles with bromanil, which stops at monoaddition using the stericallyhindered 2-isoprenylindole. This permits addition of the second indole, 7-prenylindole, which givesboth meta- and para-substituted bis-indolylquinone products. This regiochemical control problemwas solved by extension of a method we recently developed for acid-promoted addition of indoles to2,5-dichlorobenzoquinone. Under our original mineral acid conditions, reaction of 2-isoprenylindolewith dichlorobenzoquinone fails, but it succeeds with 3-bromo-2,5-dichlorobenzoquinone using aceticacid as the promoter. The regiochemistry established in such selectively bromine-substitutedquinones can be exploited in Stille couplings. As a model system, the synthesis of demethylasterriquinone A1 was accomplished using as the key step a Stille coupling of a 2,5-dibromobenzoquinonewith an (N-isoprenylindol-3-yl)tin, producing the para-substituted bis-indolylquinone exclusively.Use of a (7-prenylindole)tin in coupling with a bromo-2,5-dichloro-4-indolylbenzoquinone gives thedemethylasterriquinone B1 precursor. The dihaloquinone products of these indole/quinone couplingprocesses can be hydrolyzed to the dihydroxyquinone natural products. DemethylasterriquinoneB1 is of high recent interest as a small molecule insulin mimetic with oral anti-diabetic activity inmice.
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