Cyclohelminthol X, a Hexa-Substituted Spirocyclopropane from Helminthosporium velutinum yone96: Structural Elucidation, Electronic Circular Dichroism Analysis, and Biological Properties

• Published in: Journal of organic chemistry 2017-06, Vol.82 (11), p.5574-5582
• Main Authors: Tanaka, Shizuya, Honmura, Yuna, Uesugi, Shota, Fukushi, Eri, Tanaka, Kazuaki, Maeda, Hayato, Kimura, Ken-ichi, Nehira, Tatsuo, Hashimoto, Masaru
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Circular Dichroism; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Electrons; Helminthosporium - chemistry; HL-60 Cells; Humans; Molecular Conformation; Proteasome Endopeptidase Complex - drug effects; Structure-Activity Relationship
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b00393

Helminthosporium velutinum yone96 produces cyclohelminthol X (1), a unique hexa-substituted spirocyclopropane. Although its molecular formula and NMR spectral data resemble those of AD0157, being isolated from marine fungus Paraconiothyrium sp. HL-78-gCHSP3-B005, our detailed analyses disclosed a totally different structure. Chemical shift calculations and electronic circular dichroism spectral calculations were quite helpful to establish the structure, when those were performed based on density functional theory. The carbon framework of cyclohelminthols I–IV is found at the C1–C8 propenylcyclopentene substructure of 1. Thus, 1 is assumed to be biosynthesized by cyclopropanation between an oxidized form of cyclohelminthol IV and a succinic anhydride derivative 4. Cytotoxicity for two cancer cell lines and proteasome inhibition efficiency are measured.