title: Synthesis, isolation, stereostructure and cytotoxicity of paclitaxel analogs from cephalomannine.
abstract: Four paclitaxel derivatives were afforded by preparative HPLC separation of two pairs of diastereoisomers, which were obtained by catalytic hydrogenation and epoxidation of the C-13 side-chain double bond of cephalomannine, a naturally occurring paclitaxel analog. The four paclitaxel derivatives were analyzed using NMR, CD spectroscopy, and side-chain hydrolysis in order to measure their optical rotations and GC characteristics. In this way, the stereoconfigurations of the products were determined. Evaluation of the compounds' activity indicated that they had differing cytotoxic activities: compound 5 had superior activity in BCG-823 tumor cells compared to paclitaxel, while compound 7 had superior activity in HCT-8 and A549 tumor cells compared to paclitaxel. These results indicate that the stereoconfiguration of the paclitaxel N-acyl side chain has a significant impact on its activity.
authors.affiliation: Department of Chinese traditional herbal, Agronomy College, Sichuan Agricultural University, No.211, Huiming Road, Wenjiang Region, Chengdu 611130, China. Electronic address: gaofeng@sicau.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D043823:Taxoids; C056348:cephalomannine; D017239:Paclitaxel
keywords: Cephalomannine; Cytotoxic activity; Paclitaxel; Side chain; Structural modification