Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures

Bioorg Chem. 2003 Aug;31(4):345-56. doi: 10.1016/s0045-2068(03)00063-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Alkenes / metabolism*
  • Biotransformation
  • Bridged-Ring Compounds / metabolism
  • Cells, Cultured
  • Diterpenes / chemistry*
  • Diterpenes / metabolism*
  • Ginkgo biloba / cytology*
  • Ginkgo biloba / metabolism*
  • Hydroxylation
  • Molecular Structure
  • Paclitaxel / chemistry
  • Plants, Medicinal
  • Substrate Specificity
  • Taxoids / chemistry
  • Taxoids / metabolism

Substances

  • Alkenes
  • Bridged-Ring Compounds
  • Diterpenes
  • Taxoids
  • taxa-4(5),11(12)diene
  • taxane
  • 10-deacetylbaccatine III
  • Paclitaxel