Syntheses of a Pair of Simplified Model Compounds of the Dihydroxycyclopentenone Core of the Kodaistatins A–D. Issue 45 (27th November 2018)

• Record Type: Journal Article
• Authors: Peter, David; Brückner, Reinhard
• Is Part Of: European journal of organic chemistry. Issue 45(2018)
• Page Start: 6256
• Page End: 6273
• Publication Date: 2018-11-27
• Subjects: Aldol reactions -- α‐Bromoketones -- Cyclopentenones -- Natural products -- Samarium enolates; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201801117
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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 product1 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. Abstract : cis/trans ‐isomeric models of the dihydroxycyclopentenone core of the kodaistatins A–D were synthesized. NMR analogies show that kodaistatin A must be trans ‐configured. A key‐step was a syn ‐selective aldol addition. An oxidation/reduction tandem furnished the β‐epimeric anti ‐aldol. Each aldol was processed to a 5‐brominated 1, 4‐diketone. The latter cyclized by an SmI2 ‐mediated aldol addition. Ensuing dehydrations delivered the cyclopentenone motive.