Six New Sesquiterpenes from Euonymus nanoides and Their Antitumor Effects

Abstract

Six new dihydro-β-agarofuran [5,11-epoxy-5β,10α-eudesm-4 (14)-ene] sesquiterpenes were isolated from the seeds of Euonymus nanoides Loes, including five with a novel substitution pattern: (1R,2S,4S,5R,7R,9S,10R)-1α-benzoyloxy-2α,15-diacetoxy-4β-hydroxy-9β-cinnamoyloxy-β-dihydroagarofuran (1), 1α-(α-methyl)-butanoyl-2α,15-diacetoxy-4β-hydroxy-9β-(β-)furoyloxy-β-dihydroagarofuran (2), 1α,2α-di-(α-methyl)-butanoyl-4β-hydroxy-9β-(β-)furoyloxy-15-acetoxy-β-dihydroagarofuran (3), 1α-(α-methyl)-butanoyl-2α-(α-methyl)-propynoyloxy-4β-hydroxy-9β-(β-)furoyloxy-15-acetoxy-β-dihydroagarofuran (4) and 1α,2α, 9β-tri-(β-)furoyloxy-4β-hydroxy-15-acetoxy-β-dihydroagarofuran (5). The other dihydroagarofuran sesquiterpene was 1α,2α,6β,15-tetraacetoxy-3α-(α-methyl)-butanoyl-4β-hydroxy-9β-(β-)furoyloxy-β-dihydroagarofuran (6). The structures of 1 - 6 were elucidated by means of ¹H- and ¹³C-NMR spectroscopic studies, including 2D heteronuclear COSY (HMQC), long-range correlation spectra with inverse detection (HMBC), ¹H-¹H COSY and NOESY. The absolute configuration of compound 1 was determined by application of the CD exciton chirality method. Six compounds were evaluated for their in vitro antitumor effects (IC₅₀ values: 27.71 - 50.69 μg/mL) and the structure-activity relationship is discussed.

Key words

Euonymus nanoides - Celastraceae - sesquiterpene - β-dihydroagarofuran - CD exciton chirality method - antitumor activity

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