Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States.
J Am Chem Soc. 2024 Sep 25;146(38):26351-26359. doi: 10.1021/jacs.4c09068. Epub 2024 Sep 12.
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.
本文描述了五环苯并萘并二酮型 II 聚酮抗生素福米霉素 H 的首次全合成。该合成的一个关键特点是通过钌催化的α-酮醇-苯并环丁烯酮[4+2]环加成反应实现四环核心的收敛性、区域选择性组装。二醇环加成产物的双脱水提供了一个非手性烯酮，该烯酮经不对称亲核环氧化和进一步操作，以对映体富集的形式提供前体四环三氯化物。随后，四环三氯化物的化学选择性和非对映选择性铃木交叉偶联引入 E 环，完成全合成。两个模型化合物的单晶 X 射线衍射分析表明，最初分配的轴向手性 C6-C7 键的立体化学可能需要修正。
