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

Abstract

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.

Structure of two purple pigments, catechinopyranocyanidins A and B from the seed-coat of the small red bean, Vigna angularis

“…As shown in Table S2, the obtained chemical shift values of C5, C7″, and C4‴ in the 5-keto form agree with the experimental data, whereas the other forms show considerable divergence. The 5-keto form affords the smallest root mean square deviation (RMS), 2.98 ppm (Table S2), which is around the accuracy level in this method 18 . In contrast, the RMS values of C7″-keto and C4‴-keto forms are 6.06 and 8.16 ppm, respectively, (Table S2), which were considerably above the allowable level.…”

“…Recently, the remarkable progress in theoretical calculations has enabled the use of computed electronic circular dichroism (ECD) in the determination of the absolute configuration of natural products 18,19,22 . We applied this methodology to determine the absolute configurations of C2 and C3 in 2 and 3 .…”

Spirocyclic Motifs in Natural Products

“…In 2017, a novel condensed [2.4.0] spirocycle ( 8 ) was reported [12]. It was isolated and characterized among the secondary metabolites of the Helminthosporium velutinum plant and was named cyclohelminthol X (Figure 3).…”

“…It was isolated and characterized among the secondary metabolites of the Helminthosporium velutinum plant and was named cyclohelminthol X (Figure 3). This compound was shown to inhibit the growth of a human colon adenocarcinoma (COLO201) cell line with moderate potency (IC 50 = 16 μM), and, much more potently (IC50 = 0.35 μM)—leukemia HL60 cell line [12].…”

Spirocyclic derivatives as antioxidants: a review

“…[2.4.0] Spirocyclic system (A) [2.4.0] Spirocyclic system (A); compounds of synthetic origin Heterocyclic spiropyran compounds are of great biological and medicinal interest; they have been reported as inhibitors of the growth of human colon adenocarcinoma and the HL-60 p leukemia cell line and the production of the HIV-1 p-24 virus, 13,14 in addition to acting as strong vasopressin antagonists. 15 In 2011, the synthesis of spiro [indole-3,2-oxirane]-30benzoyl-2-(1H)-uorinated compounds (A1-A3) was reported, and their AO activities were determined through nitric oxide (NO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) tests.…”