Two pairs of rare naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives from the red alga Chondria crassicaulis

Abstract

Two pairs of rare naturally occurring racemic lipids, (±)-4,7-dihydroxy-4-methyl-2,5-heptanedione (1), and (±)-7-butoxy-4-hydroxy-4-methyl-2,5-heptanedione (2) were isolated from the red alga Chondria crassicaulis Harv. The structures of the racemic mixtures of 1 and 2 were elucidated by detailed spectroscopic techniques, including 1D and 2D NMR (¹H and ¹³C NMR, ¹H–¹H COSY, HSQC, and HMBC) as well as mass spectrometry and optical rotation experiments, and by comparison with data for related known analogs. This is the first report of naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives. Antifungal, PTP1B inhibitory, and receptor tyrosine kinase inhibitory activities of these two compounds were investigated. The results showed that compounds 1 and 2 exhibited good selective inhibition against RET tyrosine kinase activity with IC₅₀ values of 9.56 and 8.93 μM, respectively. Compound 1 also displayed moderate antifungal activity against Cryptococcus neoformans (32609), showing a MIC₈₀ value of 32 μg/ml.

Keywords:

• Red algae
• Chondria crassicaulis
• 4-hydroxy-4-methyl-2,5-heptanedione
• antifungal activity
• receptor tyrosine kinase inhibitory activity