Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.
Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28409, United States.
J Nat Prod. 2024 Aug 23;87(8):2095-2100. doi: 10.1021/acs.jnatprod.4c00649. Epub 2024 Jul 23.
Wheldone is a fungal metabolite isolated from the coculture of and , displaying cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methyl-bicyclo[5.4.0]undeca-3,5-diene scaffold with a 2-hydroxy-1-propanone side chain and a 3-(2-(1-hydroxyethyl)-2-methyl-2,5-dihydrofuran-3-yl)acrylic acid moiety. Upon further examination, minor inconsistencies in the data suggested the need for the structure to be revisited. Thus, the structure of wheldone has been revised using an orthogonal experimental-computational approach, which combines 1,1-HD-ADEQUATE NMR experiments, DFT-GIAO chemical shift calculations, and single-crystal X-ray diffraction (SCXRD) analysis of a semisynthetic bromobenzylamide derivative, formed via a Steglich-type reaction. The summation of these data now permits the unequivocal assignment of both the structure and absolute configuration of the natural product.
Wheldone 是一种从 和 的共培养物中分离得到的真菌代谢产物，对乳腺癌、黑色素瘤和卵巢癌细胞系表现出细胞毒性。最初，其结构被表征为一种不寻常的 5-甲基-双环[5.4.0]十一烷-3,5-二烯支架，带有 2-羟基-1-丙酮侧链和 3-(2-(1-羟基乙基)-2-甲基-2,5-二氢呋喃-3-基)丙烯酸部分。进一步检查时，数据中的细微不一致表明需要重新考察其结构。因此，使用正交实验-计算方法修订了 wheldone 的结构，该方法结合了 1,1-HD-ADEQUATE NMR 实验、DFT-GIAO 化学位移计算以及通过 Steglich 型反应形成的半合成溴苄基酰胺衍生物的单晶 X 射线衍射 (SCXRD) 分析。这些数据的总和现在允许对天然产物的结构和绝对构型进行明确的赋值。
