| Abstract
| - A concise total synthesis of citreofuran 4 is described, a structurally unique octaketide derivativebelonging to the curvularin family. Key steps involve the elaboration of orsellinic acid methyl ester5 to acid 14, which converts, on attempted formation of the corresponding acid chloride, to the3-alkoxyisocoumarin derivative 20. This heterocycle can be used as an activated ester to give ketone21 on treatment with 3-pentynylmagnesium bromide in the presence of TMSCl as the activatingagent. Ring- closing alkyne metathesis (RCAM) of diyne 21 catalyzed by (tBuO)3W⋮CCMe3 affordsthe strained cycloalkyne 22. Treatment with acid renders its triple bond susceptible to nucleophilicattack by the adjacent carbonyl group, thus leading to a transannular cycloaromatization withformation of the intact skeleton of citreofuran. An X-ray crystallographic study reveals conformational details about this natural product. Finally, it is shown that 4 as well as its protected precursor23 are able to cleave double-stranded DNA under oxidative conditions.
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