Antifungal Enantiomeric Styrylpyrones from Sanrafaelia ruffonammari and Ophrypetalum odoratum

Abstract

Phytochemical investigation of Sanrafaelia ruffonammari Verd and Ophrypetalum odoratum Diels that belongs to the rare genera confined to East African coastal forests led to the isolation of enantiomeric styrylpyrone dimer, (±)-5-methoxy-7-phenyl-[4-methoxy-2-pyronyl]-1-(E)-styryl-2-oxabicyclo-[4.2.0]-octa-4-en-3-one (1) alongside (+)-6-styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the enantiomeric (+)- (3) and (−)-6-styryl-7,8-dihydroxy-4-methoxypyran-2-ones (4). Their structures were established by means of spectroscopic methods. In this paper we reveal for the first time the occurrence of styrylpyrones in East African biodiversity. (+)-6-Styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the dihydroxystyrylpyrone enantiomer (3) showed in vitro antifungal activity against Candida albicans at a concentration of 24.4 and 26.2 µM with zones of inhibition of 17 and 9 mm, respectively. Compound 2 exhibited strong activity in the brine shrimp test with LC50 = 1.7 µg/mL. Their high cytotoxic and antifungal activities render them candidates for further scientific attention for drug development programs against cancer and microbial infections.

Natural Enantiomers: Occurrence, Biogenesis and Biological Properties

“…Compounds 463a/463b from Dendrobium nobile were identified as a pair of spirodiketone enantiomers in 2016 [218]. Styrylpyrone monomer (464a/464b) and dimer (465) enantiomers were reported from Sanrafaelia ruffonammari and Ophrypetalum odoratum, respectively, but the dimer 465 was only obtained as a racemate without further chiral separation [219]. Compounds 466a/466b are a pair of enantiomeric 2,3-dihydro-1H-indene derivatives discovered from Streblus indicus in 2016 [220].…”

“…Few reports have been published on the antifungal activities of the enantiomers mentioned in this review, although a handful of examples have shown about two-fold bioactivity differences between enantiomers (Table 5). The δ-lactone enantiomer (−)-464a was reported to display inhibitory activity against Candida albicans with an MIC of 26.4 µM, while its antipodal enantiomer (+)-464b was considered inactive [219]. In addition, both levorotary enantiomers of compounds (±)-483 and (±)-484 exhibited better antifungal activity again C. albicans than their respective dextrorotary isomers [229], and similar effect against Fusarium solani was also recorded for the indole-piperidine enantiomer pair (±)-524 [256].…”