I. Preparation and Biological Effects of Ceanothic acid derivatives II. Chemical constituents from the leaves of Colubrina asiatica(L.) Brongn.

• Main Authors: Chen, Wen chuan, 陳文娟
• Other Authors: Lee Shoei-Sheng
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/22935145211961616629

碩士 === 國立臺灣大學 === 藥學系研究所 === 85 === I. Preparation and Biological Effects of Ceanothic acid derivatives II. Chemical constituents from the leaves of Colubrina asiatica (L.) Brongn. Part I Betulinic acid, widely distributed in the plant kingdom, has been reported to possess cytotoxic and anti-HIV activities. The structurally similar natural product ceanothic acid, abundant in the hamnaceous plant Paliurus ramosissimus , possesses a carboxylic acid substitution at C-1 and a five-membered A ring instead of six-membered as in betulinic acid. To further explore the anti-HIV activity and cytotoxicity of betulinic acid derivatives, part I of this thesis was aimed to prepare2-norceanothic acid analogues from ceanothic acid, and assay their activities against human immunodeficiency virus reverse transcriptase (HIV-RT) and cancer cell lines. 2-Norceanothane and ceanothane derivatives were prepared starting from ceanothic acid 2,28-dibenzyl ester. Major reaction steps included PCC oxidation, debenzylation with Lithium iodide in γ-collidine under reflux, LiAlH4 reduction, and dehydration. The biological tests demonstrated that these compounds had no significant inhibition against HIV-RT, but betulinic acid and 2-norceanothane derivatives 5,6,10 (10 mg/ml) exhibited significant inhibitory activity against OV-3 and HeLa cells. From the value of IC50, betulinic acid was found to be the most potent one, IC50 0.88 mg/ml and 0.81 mg/ml on OV-3 and HeLa cells, respectively. Therefore, the six-membered A ring played a key role in cytotoxic activity. Part II Colubrina asiatica (L.) Brongn., a rhamnaceous plant, is widely distributed in tropical and subtropical areas. The jujubogenin glycoside possessing sedative effect was reported to be rich in this plant. The microbial transformation of lanosterol possessing steroid nucleus has been carried out, and the dammarane type jujubogenin also contains steroid nucleus. Consequently , the second part of this thesis was aimed to study continuously the isolation of jujubogenin glycosides from C. asiatica (L.) Brongn. and to develop method, in preparation of the genuine aglycone jujubogenin from the glycosides, for further microbial transformation or for preparing the bioactive derivatives. The chloroform soluble fraction of the EtOH extract of the leaves was defatting by trituration with hexane. After that this fraction was separated by combination of partition chromatography (C.P.C. and D.C.C.C.), Sephadex LH-20, lobar RP-18, and the conventional adsorption chromatography to give six compounds. Of these four are dammarane glycosides, i.e. colubrin (13), II-65-1 (14), II-93-3 (15), II-55-3 (16); two are flavonoid glycosides, i.e. rutin (17) and kaempferol-3-O-rutinoside (18). In addition, part of chloroform soluble fraction was passed through a Sephadex LH-20 column to remove flavonol glycosides. The remaining saponin fraction was oxidatively degraded under strong base conditions to give the genuine aglycone and jujubogenin(20). Structural elucidation of these comounds was based on elaborate spectral analysis including 2D NMR techniques. Among these, compounds 14-16 are novel natural products.