摘要
Abstract
The kinetics of the Michael addition reaction among four ent-kaurenes, i. e. oridonin ( 1 ) and ponicidin (2) from Isodon rubescens (Hemsley) H. Hara,1,14-diacetyl oridonin (1a),1,6-diacetyl ponicidin (2a) and ethyl 4-nitrobenzoylacetate ( ENBA) was investigated for the first time in order to conveniently predict their antitumor activity. Stoichiometric analysis indicated that the reaction between these ent-kaurenes and ENBA followed second order kinetics. The descending order of reaction rates of the four ent-kaurenes was clearly showed as 1,1a, 2 and 2a. According to the Arrhenius equation,the activation energy of the overall reaction between oridonin,ponicidin and ENBA was (38. 7 ± 5. 8) and (46. 8 ± 7. 1) kJ/mol,respectively. A new major adduct named as nitrobenoridonin (1b) of oridonin and ENBA was isolated and identified as 1α, 6β, 7β, 14β-tetrahydroxy-7α, 20-epoxy-17-( 2-( 3-( 4-nitrophenyl ) )-3-oxo-ethylpropanoate)-kaurane-15-one based on the spectroscopic evidence such as NMR. Moreover,these compounds were evaluated for their cytotoxicities against four cancer cell lines and exhibited significant in vitro antitumor activities. The results indicated that the order of in vitro antitumor activities of the four ent-kaurenes generally consistented with the order of their Michael addition reaction activities. A hypothetical conclusion was proposed that the antitumor activities of ent-kaurenes were probably related to their Michael addition reaction activities. Based on these novel findings,a convenient method for evaluating the antitumor activities of ent-kaurenes should be established according to their Michael addition reaction activities.关键词
迈克尔加成反应/反应动力学/抗肿瘤活性/对映-贝壳杉烯/冬凌草甲素/冬凌草乙素Key words
Michael addition reaction/reaction kinetics/antitumor activity/ent-kaurene/oridonin/ponicidin分类
化学化工
