Isolation and synthesis of novel antimicrobial chromene derivatives from Psorothamnus fremontii

Bioassay-guided fractionation of the methanol extract of the Native American plant Psorothamnus fremontii (Fabaceae) yielded three new chromene derivatives with a unique epoxy functionality on the ring system. The structures of the new compounds were established by interpretation of spectroscopic data as 6-hydroxy-7-isobutyryl-3,3,5-trimethyl-1a,2-dihydro-3H,8H-oxireno[2,3-d]chromen-8-one (1), 6-hydroxy-3,3,5-trimethyl-7-(2-methylbutanoyl)-1a,2-dihydro-3H,8H-oxireno[2,3-d]chromen-8-one (2), and 6-hydroxy-7-isobutyryl-3,3-dimethyl-5-(3-methylbut-2-en-1-yl)-1a,2-dihydro-3H,8H-oxireno[2,3-d]chromen-8-one (3). The three compounds were active against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) in a range of 2.7 – 12.0 µg/mL, with 3 being the most active with IC₅₀s of 3.0 and 2.7 µg/mL, respectively. Compound 3 was synthesized using a simple four-step scheme that could be used to generate additional analogues.