An efficient conversion of taxinine to taxinine NN-1, an anticancer agent and a modulator of multidrug-resistant tumor cells.
Taxinine NN-1 (1), which shows significant activities as a modulator of multidrug-resistant cancer cells and as an anticancer agent in an in vitro assay based on a HCC panel, was synthesized in order to obtain sufficient material for a higher order bioassay from easily available taxinine (2). The synthesis was achieved via intermediate 8, which was derived from 2 by the stepwise protection of a 9,10-dihydroxyl group as acetonide and a 2-hydroxyl group as a MOM protecting group. The temporary elimination of a cinnamoyl group at C-5 of 8 and successive reduction of a C-13 carbonyl group of the resulting 9 gave 10 and the undesired 13-epimer 11. The latter was recycled to 9 by oxidation with MnO(2). Stepwise acetylation and cinnamoylation at C-13 and C-5 of 10 and successive deprotection of the acetonide protecting group at C-9,10 of the resulting 13 gave diol 14. Diacetylation of 14 and deprotection of the MOM protecting group at C-2 of the resulting 15 gave 1. The overall yield of 1 was 45% in 11 steps from 2.
Zhang
Shujun
S
Department of Chemistry and Chemical Engineering, Niigata University, Ikarashi 2-8050, Niigata 950-2181, Japan.
Wang
Jinlan
J
Hirose
Katutoshi
K
Ando
Masayoshi
M
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D043823:Taxoids; C473165:taxinine NN-1; C473166:taxinine; D017239:Paclitaxel