Structure Elucidation and Confirmation of Phloroglucinols from the Roots of Garcinia dauphinensis by Comparison of Experimental and Calculated ECD Spectra and Specific Rotations.

Eight phloroglucinols from Garcinia dauphinensis were recently reported to have good to moderate antiplasmodial and anticancer activities, consistent with other phloroglucinol derivatives isolated from natural sources. Chiroptical properties were previously calculated and compared to experimental data for compound 2 as a means to deduce its absolute configuration. Tentative assignments for the remaining compounds were also reported based on these data. In order to arrive at stereochemical assignments for phloroglucinols 1 and 3-8, ECD spectra and specific rotations were computed for all stereoisomers of each compound. Molecular orbital analyses were also carried out for the most energetically favorable conformers of each compound. Absolute configurations are reported for all eight phloroglucinols for the first time.

Phloroglucinols from the Roots of Garcinia dauphinensis and Their Antiproliferative and Antiplasmodial Activities.

Garcinia dauphinensis is a previously uninvestigated endemic plant species of Madagascar. The new phloroglucinols dauphinols A-F and 3'-methylhyperjovoinol B (1-7) and six known phloroglucinols (8-13) together with tocotrienol 14 and the three triterpenoids 15-17 were isolated from an ethanolic extract of G. dauphinensis roots using various chromatographic techniques. The structures of the isolated compounds were elucidated by NMR, MS, optical rotation, and ECD data. Theoretical ECD spectra and specific rotations for 2 were calculated and compared to experimental data in order to assign its absolute configuration. Among the compounds tested, 1 showed the most promising growth inhibitory activity against A2870 ovarian cancer cells, with IC50 = 4.5 ± 0.9 µM, while 2 had good antiplasmodial activity against the Dd2 drug-resistant strain of Plasmodium falciparum, with IC50 = 0.8 ± 0.1 µM.

Antiplasmodial Sesquiterpenoid Lactones from Trichospira verticillata: Structure Elucidation by Spectroscopic Methods and Comparison of Experimental and Calculated ECD Data.

A dichloromethane extract of Trichospira verticillata from the Natural Products Discovery Institute was discovered to have good antiplasmodial activity (IC50 ∼5 µg/mL). After purification by liquid-liquid partition and C18 reversed-phase HPLC, four new germacranolide-type sesquiterpenoid lactones named trichospirolides A-D (1-4) were isolated. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and MS data. The relative and absolute configurations were assigned based on a comparison of calculated and experimental ECD and UV spectra, specific rotations, internuclear distances, and coupling constants for all possible diastereomers for each compound. Among these four compounds, the conjugated dienone 1 displayed the most potent antiplasmodial activity, with an IC50 value of 1.5 µM.

That Little Extra Kick: Nonadiabatic Effects in Acetaldehyde Photodissociation.

The effect of nonadiabatic transitions on branching ratios, kinetic and internal energy distribution of fragments, and reaction mechanisms observed in acetaldehyde photodissociation is investigated by nonadiabatic molecular dynamics (NAMD) simulations using time-dependent hybrid density functional theory and Tully surface hopping. Homolytic bond breaking is approximately captured by allowing spin symmetry to break. The NAMD simulations reveal that nonadiabatic transitions selectively enhance the kinetic energy of certain internal degrees of freedom within approximately 50 fs. Branching ratios from NAMD and conventional "hot" Born-Oppenheimer molecular dynamics (BOMD) are similar and qualitatively agree with experiment. However, as opposed to the BOMD simulations, NAMD captures the high-energy tail of the experimental kinetic energy distribution. The extra "kick" of the nuclei in the direction of the nonadiabatic coupling vector results from nonadiabatic transitions close to conical intersections. From a mechanistic perspective, the nonadiabatic effects favor asynchronous over synchronous fragmentation and tend to suppress roaming.