Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures.
Three C-14 oxygenated taxanes isolated from callus cultures of Taxus spp., 2alpha,5alpha,10beta,14beta-tetra-acetoxy-4(20),11-taxadiene 3, 2alpha,5alpha,10beta-triacetoxy-14beta-propionyloxy-4(20),11-taxadiene 4, 2alpha,5alpha,10beta-triacetoxy-14beta-(2-methylbutyryl)-oxy-4(20),11-taxadiene 5, and three deacetylated derivatives of 3, 10beta-hydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene 6, 14beta-hydroxy-2alpha,5alpha,10beta-triacetoxy-4(20),11-taxadiene 7, 10beta,14beta-dihydroxy-2alpha,5alpha-diacetoxy-4(20),11-taxadiene 8, could all be regio- and stereo-selectively hydroxylated at the 9alpha-position by Ginkgo cell suspension cultures to yield a series of new 9alpha,14beta-dihydroxylated taxoids. The effects of functional groups, especially at C-14 of the substrates, on the biotransformation were also investigated. The results revealed that substrates with an acetoxyl group at C-14 could be more efficiently 9alpha-hydroxylated than those with a longer ester chain or a hydroxyl group at C-14. An acetoxyl or hydroxyl group at C-10 had no effect on the conversion rates of the substrates, but substrates with the hydroxyl group (compared with the acetoxyl analogues) could be converted into 9alpha-hydroxylated products more easily.
Dai
Jungui
J
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38#, 100083, Beijing, PR China.
Ye
Min
M
Guo
Hongzhu
H
Zhu
Weihua
W
Zhang
Dayong
D
Hu
Qiu
Q
Zheng
Junhua
J
Guo
Dean
D
D000475:Alkenes / Q000737:chemistry* / Q000378:metabolism*; D001711:Biotransformation; D001952:Bridged-Ring Compounds / Q000378:metabolism; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism*; D020441:Ginkgo biloba / Q000166:cytology* / Q000378:metabolism*; D006900:Hydroxylation; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry; D010946:Plants, Medicinal; D013379:Substrate Specificity; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism
D000475:Alkenes; D001952:Bridged-Ring Compounds; D004224:Diterpenes; D043823:Taxoids; C093125:taxa-4(5),11(12)diene; C080625:taxane; C042213:10-deacetylbaccatine III; D017239:Paclitaxel