Syntheses of a Pair of Simplified Model Compounds of the Dihydroxycyclopentenone Core of the Kodaistatins A–D

The kodaistatins A–D ( 1–4 ) are natural products from Aspergillus terreus with the potential of representing leads for a novel cure of type‐2 diabetes. They possess an unusually and highly substituted dihydroxycyclopentenone core. Whether its OH groups are cis ‐ or trans ‐configured remained unknown by spectroscopy. Previous syntheses of kodaistatin model compounds ( cis ‐ 5 , cis ‐ and trans ‐ 6 ) allowed to make NMR comparisons with kodaistatin A ( 1 ). They led to the insight that the natural product 1 must be a trans ‐diol. These findings are corroborated by the synthesis and ensuing NMR study of another pair of cis/trans ‐isomeric kodaistatin models ( cis ‐ and trans ‐ 7 ) described here. Its first key‐step was a syn ‐selective aldol addition. An oxidation/reduction sequence allowed reaching to the corresponding anti ‐aldol. Each aldol furnished a kodaistatin model in eight additional steps. The most noteworthy transformation was an Sm II ‐induced intramolecular aldolization of a bromodiketone.