Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Gunma University School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
J Nat Prod. 2022 Jul 22;85(7):1697-1703. doi: 10.1021/acs.jnatprod.2c00137. Epub 2022 Jun 16.
Phytohabitols A-C (-), new terminally δ-lactonized linear polyketides, were isolated from the culture extract of a rare actinomycete of the genus . The structures of -, substituted with multiple methyl and hydroxy groups on a conjugated and a skipped diene-containing backbone, were elucidated by NMR and MS spectroscopic analyses. The absolute configuration of was determined by chemical derivatization and chiral anisotropic analysis, coupled with ROESY and -based configuration analysis. In addition, closely similar H and C NMR data and optical rotations among - supported the same stereochemistry of these polyketides. The related streptomycetes metabolites lagunapyrones B, C, and D have α-pyrone rings on the linear part in place of the δ-lactone, but their chirality at the C19-C21 stereocenters were opposite from those described here, posing a question on the previous assignment made solely by comparison of the optical rotations of four possible diastereomers. Compounds - inhibited migration of cancer cells with IC values of 15, 11, and 8.3 μM, respectively, at noncytotoxic concentrations. In addition, - displayed potent antitrypanosomal activity against with IC values of 12, 6.4, and 18 μM, comparable to a commonly used therapeutic drug, benznidazole (IC 16 μM).
植物Habitol A-C(-)，新型末端 δ-内酯化的线性聚酮类化合物，从罕见放线菌属的培养提取物中分离得到。通过 NMR 和 MS 光谱分析阐明了结构，其中取代了多个甲基和羟基，在共轭和跳过二烯的骨架上。通过化学衍生化和手性各向异性分析，结合 ROESY 和基于的构型分析，确定了的绝对构型。此外，-之间相似的 H 和 C NMR 数据和旋光性支持这些聚酮类化合物具有相同的立体化学。相关的链霉菌代谢物 lagunapyrones B、C 和 D 在线性部分具有α-吡喃酮环，而不是 δ-内酯，但它们在 C19-C21 立体中心的手性与这里描述的相反，这对仅通过比较四个可能的非对映异构体的旋光性来进行的先前分配提出了一个问题。化合物 - 在非细胞毒性浓度下分别以 15、11 和 8.3 μM 的 IC 值抑制癌细胞迁移。此外，- 对 表现出强大的抗锥虫活性，IC 值为 12、6.4 和 18 μM，与常用的治疗药物苯并咪唑（IC 16 μM）相当。
