Six New Sesquiterpenes fromEuonymus nanoidesand Their Antitumor Effects

Abstract

Six new dihydro-beta-agarofuran [5,11-epoxy-5beta,10alpha-eudesm-4 (14)-ene] sesquiterpenes were isolated from the seeds of Euonymus nanoides Loes, including five with a novel substitution pattern: (1 R,2 S,4 S,5 R,7 R,9 S,10 R)-1alpha-benzoyloxy-2alpha,15-diacetoxy-4beta-hydroxy-9beta-cinnamoyloxy-beta-dihydroagarofuran ( 1), 1alpha-(alpha-methyl)-butanoyl-2alpha,15-diacetoxy-4beta-hydroxy-9beta-(beta-)furoyloxy-beta-dihydroagarofuran ( 2), 1alpha,2alpha-di-(alpha-methyl)-butanoyl-4beta-hydroxy-9beta-(beta-)furoyloxy-15-acetoxy-beta-dihydroagarofuran ( 3), 1alpha-(alpha-methyl)-butanoyl-2alpha-(alpha-methyl)-propynoyloxy-4beta-hydroxy-9beta-(beta-)furoyloxy-15-acetoxy-beta-dihydroagarofuran ( 4) and 1alpha,2alpha, 9beta-tri-(beta-)furoyloxy-4beta-hydroxy-15-acetoxy-beta-dihydroagarofuran ( 5). The other dihydroagarofuran sesquiterpene was 1alpha,2alpha,6beta,15-tetraacetoxy-3alpha-(alpha-methyl)-butanoyl-4beta-hydroxy-9beta-(beta-)furoyloxy-beta-dihydroagarofuran ( 6). The structures of 1 - 6 were elucidated by means of (1)H- and (13)C-NMR spectroscopic studies, including 2D heteronuclear COSY (HMQC), long-range correlation spectra with inverse detection (HMBC), (1)H- (1)H 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 (IC (50) values: 27.71 - 50.69 microg/mL) and the structure-activity relationship is discussed.