Trigocherrin A, the First Natural Chlorinated Daphnane Diterpene Orthoester from Trigonostemon cherrieri

Abstract

Trigocherrin A, a chlorinated and highly oxygenated daphnane diterpenoid orthoester (DDO), was isolated from the bark of Trigonostemon cherrieri. Trigocherrin A is the first example of a naturally occurring halogenated DDO. Its structure was elucidated by comprehensive analysis of NMR spectroscopic data, and its absolute configuration was determined by comparison of experimental and theoretically calculated ECD spectra. Trigocherrin A exhibited a potent and selective effect against Chikungunya virus in Vero cells.

Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri

“…The dichlorovinyl moiety observed in compounds 1-6 and 10 is particularly rare in natural products and, to the best of our knowledge, this is the second time that this functionality has been encountered in higher plants (Chan et al, 2000). The biosynthetic origin of these chlorine atoms is not elucidated yet but we hypothesized the implication of a non-heme iron, O 2 , a-ketoglutarate-dependent halogenase (Allard et al, 2012). The verification of this hypothesis would require in depth study of the plants genetic material.…”

“…Furthermore, the dichlorovinyl moiety is particularly scarce in higher plants since it has only been found in the structure of chingazumianine, a probable artifactual alkaloid isolated from the species Corydalis koidzumiana (Chan et al, 2000). The possible implication of a specific type of enzyme (non-heme iron, O 2 , a-ketoglutarate-dependent halogenase) in the halogenation process of these natural products has been discussed in our previous publication (Allard et al, 2012).…”

“…Since all compounds share the same DDO backbone, and given that the structure of trigocherrin A (1) has been fully characterized, including its absolute configuration (Allard et al, 2012), only the nature and spatial positions of the substituents on the daphnane core will be discussed in detail. In the NOESY spectra of trigocherrins A and B (1, 2), and trigocherriolide A (7), a set of cross peaks, including a clear correlation between OH-4 and H-8, which indicated a b-orientation of the hydroxy group at C-4, allowed to determine their relative configuration (Figs.…”

“…From the species T. cherrieri, we recently reported the isolation and structural characterization of trigocherrin A (1) an unusual chlorinated daphnane diterpenoid orthoester (DDO) possessing a selective and potent antiviral activity against the chikungunya virus replication in cellulo (Allard et al, 2012).…”

Two halosesquiterpenes from Laurencia composita

“…3) using the timedependent density function theory (TD-DFT) method at the B3LYP/6-31G(d) level. [12][13][14] Thus, an absolute configuration of 2S, 3S, 5S, 6R, 7R, and 10R was assigned to both 1 and 2. It was interesting that the experimental ECD spectrum of 2 exhibited a redshift (ca.…”