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为了快速、简便地评价冬凌草(Isodon rubescens(Hemsley)H.Hara)活性成分的抗肿瘤活性,以冬凌草活性成分冬凌草甲素和冬凌草乙素及其乙酰化产物与对硝基苯甲酰乙酸乙酯(ENBA)进行迈克尔加成反应,以反应动力学得出迈克尔加成反应的反应活性,首次以反应活性预测了对冬凌草甲素(1)、冬凌草乙素(2)、1,14-二乙酰基冬凌草甲素(1a)和1,6-二乙酰基冬凌草乙素(2a)4个对映-贝壳杉烯的抗肿瘤活性。结果表明:4种活性成分的迈克尔加成反应均符合二级动力学方程,反应活性1>1a>2>2a,根据阿伦尼乌斯公式,测得冬凌草甲素活化能(Ea)为(38.7±5.8)kJ/mol,冬凌草乙素Ea为(46.8±7.1)kJ/mol。采用~1H NMR和~(13) C NMR等波谱技术鉴定冬凌草甲素与ENBA经迈克尔加成反应得到的新化合物为1α,6β,7β,14β-四羟基-7α,20-环氧-17-(2-(3-(4-硝基苯基))-3-氧-丙酸乙酯)-对映贝壳杉烷-15-酮,命名为nitrobenoridonin(1b)。4个对映-贝壳杉烯具有较强的体外抗肿瘤活性,经测定它们的抗肿瘤活性大小依次为1>1a>2>2a,与其迈克尔加成反应活性排序一致,表明迈克尔加成反应活性与抗肿瘤活性之间存在较好的相关性,可以通过测定迈克尔加成反应活性预测对映-贝壳杉烯的抗肿瘤活性。
In order to evaluate the antitumor activity of Isodon rubescens (Hemsley) H.Hara rapidly and easily, the antitumor activity of Rubescens Alabara and Rubescens B and its acetylated products Michael reaction of ethyl nitrobenzoyl acetate (ENBA) was carried out. The reaction kinetics was used to derive the Michael addition reaction reactivity. For the first time, the activity of oridonin (1), rubescens The antitumor activity of 4 enantiomers, such as acetophenone (2), 1,14-diacetyl oridonin (1a) and 1,6-diacetyl ornithinacetate (2a), was studied. The results showed that the Michael addition reactions of the four active ingredients all fit the second order kinetics equation and the reactivity 1> 1a> 2> 2a. According to the Arrhenius formula, the activation energy of Rubescensine A (Ea) (38.7 ± 5.8) kJ / mol, and that of Rubescens B (46.8 ± 7.1) kJ / mol. The new compounds were identified as 1α, 6β, 7β, 14β-tetrahydroxy-7α, 20-epoxy- 17- (2- (3- (4-Nitrophenyl)) - 3-oxo-propionic acid ethyl ester) -benzylolazin-15-one, designated as nitrobenoridonin (1b). The four enantiomer-kaurene possessed strong antitumor activities in vitro. Their antitumor activities were determined in order of 1> 1 a> 2> 2 a, consistent with their order of Michael addition reaction activity, indicating that Michael addition reaction activity There is a good correlation between anti-tumor activity and antitumor activity, and the anti-tumor activity of the ent-kaurene can be predicted by measuring the Michael addition reaction activity.