Profiling new taxanes using LC/MS and LC/MS/MS substructural analysis techniques

Abstract

Abstract A rapid and systematic protocol based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural analysis techniques was utilized to identify novel taxane structures. Analyses of Taxus brevifolia, T. baccata and T. hicksii extracts and process intermediates have provided data for 24 novel taxanes and two side‐chain derivatives. Profiling of novel taxanes was based on comparing the mass spectrometric characteristics of unknown taxanes with the paclitaxel substructural ‘template’. The profiled structures incorporate four modifications from the paclitaxel template in the core and side‐chain substructures corresponding to: (i) substitution of the 3′ amide of the side‐chain with a series of homologs from acetamide through heptamide, (ii) substitution on the paclitaxel core substructure, (iii) absence of the paclitaxel side‐chain, and (iv) absence of the paclitaxel core. Detailed analytical data obtained for these novel compounds using a protocol based on LC/MS and LC/MS/MS are reported, including: high‐performance liquid chromatography (HPLC) relative retention time obtained under standard conditions, molecular weight, and MS/MS product ions indicative of specific substructures of the molecule.