Five Pairs of Meroterpenoid Enantiomers from Rhododendron capitatum

Abstract

Chemical investigation on the aerial parts of Rhododendron capitatum resulted in the discovery of five enantiomeric pairs of new meroterpenoids, (+)-/(-)-rhodonoids C (1a and 1b), E (3a and 3b), F (4a and 4b), and (-)-/(+)-rhodonoids D (2a and 2b) and G (5a and 5b). These enantiomeric pairs existed as partial racemates in a plant and were obtained by chiral HPLC separation. Their structures with absolute configurations were assigned by spectroscopic data, single-crystal X-ray diffraction, and ECD analysis. Compounds 1a and 1b are the first pair of meromonoterpenes incorporating an unprecedented 6/6/6/5 ring system, and 1a showed antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Compounds 2a and 2b are the first examples of meromonoterpenes featuring a unique 6/6/5/5 ring system.

Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

“…Moreover, only 322a inhibited HSV-1 with an IC 50 value of 80.6 µM. Compounds 322a and 322b featured the unusual 6/6/6/5 tetracyclic ring core while compounds 323a and 323b bore the rather rare 6/6/5/5 tetracyclic ring system [104]. Another Rhododendron sp., viz., R. nyingchiense interestingly, also produced enantiomeric pairs of the meromonoterpenoids 327a,b-332a,b and all racemic mixtures were separated by chiral-phase HPLC.…”

Total Syntheses of (±)-Rhodonoids C, D, E, F, and G and Ranhuadujuanine B

“…Recently, Hou , reported the isolation of (±)-rhodonoids A–G (Figure ) from Rhododendron capitatum Maxim, a shrub found in the Qinghai province of China, which is used in Tibetan medicine. In addition to their unique motifs, these novel meroterpenoids possess anti-HSV-1 activity ( 1 ) and inhibitory effects on PTP1B ( 8 ).…”

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

“…Each group of terpenoids-monoterpenes, sesquiterpenes, diterpenes and triterpenes (including steroidal compounds)-gave us at least one positive hint in the search. The least abundant are monoterpenes, that are represented only by cypellocarpin C (63) isolated from E. globulus (63, arising from the combination of monocyclic monoterpene with a methylchromone), geraniol (64), here obtained from T. bovei essential oil [57], showing effects against HSV-2, both IC 50 and SI, greater than acyclovir [58], and (+)-rhodonoid C (64) (a cross-metabolite of monoterpene and polyketide [59]). In comparison to acyclovir, positive results were also obtained for cucurbitacin B (94) [73], meroditerpenes from Brazilian seaweed Stypopodium zonale 79 and 80 [67], dollabene diterpenes (85 and 86) from brown alga Dictyota pfaffi [70], which were inhibiting reverse transcriptase of HSV-1, as well as for halistanol derivatives (95)(96)(97), a steroidal type compound obtained from Brazilian marine sponge Petromica citrina [74] which, interestingly, showed a synergistic effect when tested together with acyclovir, but a lower selectivity index when tested alone.…”