1H-NMR and molecular networking-guided dereplication of phloroglucinol meroterpenoids from Cleistocalyx operculatus buds as neuraminidase inhibitors

초록

A dereplication strategy guided by 1H-NMR and molecular networking resulted in the isolation of two unusual phloroglucinols [(+)-1 and (+)-2], which possess a rare decahydro-2H-cyclopenta[i]chromene skeleton, along with five undescribed phloroglucinol meroterpenoids [(+)-3-(+)-7] from the buds of Cleistocalyx operculatus. The chemical structures of isolated compounds were determined by 1D and 2D NMR spectroscopy, ECD, X-ray crystallography, and DP4+ probability calculations. Compounds (+)-1-(+)-7 were naturally found as enantiomeric pairs, which were successfully separated using chiral phase HPLC. Structural analysis of these compounds suggested a plausible biosynthetic pathway, involving the late-stage incorporation of acetoacetyl-CoA into the 2,2,4-trimethylcinnamyl-beta-triketone core, followed by a series of functionalization steps leading to compounds (+)-1-(+)-4. Compounds (+)-1 and (+)-2 exhibited moderate neuraminidase inhibitory activity against neuraminidase enzymes from both H1N1 and H9N2 influenza strains. Kinetic experiments suggested a noncompetitive binding mechanism for compound (+)-1.

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