Total Synthesis of the Phenylnaphthacenoid Type II Polyketide Antibiotic Formicamycin H via Regioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer [4 + 2] Cycloaddition.

Autor:	Hu G; Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States., Doerksen RS; Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States., Ambler BR; Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States., Krische MJ; Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2024 Sep 25; Vol. 146 (38), pp. 26351-26359. Date of Electronic Publication: 2024 Sep 12.
DOI:	10.1021/jacs.4c09068
Abstrakt:	The first total synthesis of the pentacyclic phenylnaphthacenoid type II polyketide antibiotic formicamycin H is described. A key feature of the synthesis involves the convergent, regioselective assembly of the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct provides an achiral enone, which upon asymmetric nucleophilic epoxidation and further manipulations delivers the penultimate tetracyclic trichloride in enantiomerically enriched form. Subsequent chemo- and atroposelective Suzuki cross-coupling of the tetracyclic trichloride introduces the E-ring to complete the total synthesis. Single-crystal X-ray diffraction analyses of two model compounds suggest that the initially assigned stereochemistry of the axially chiral C6-C7 linkage may require revision.
Databáze:	MEDLINE
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