Colchicinoids from Colchicum crocifolium Boiss.: a case study in dereplication strategies for (–)‐Colchicine and related analogues using LC‐MS and LC‐PDA techniques

Abstract

As a part of a project designed to investigate Colchicum species in Jordan, the chemical constituents of Colchicum crocifolium Boiss. (Colchicaceae) were investigated using LC-MS and LC-UV/Vis PDA. A decision tree for working with colchicinods has been developed by incorporating data from LC-UV/PDA and LC-MS. This dereplication strategy draws upon the UV/PDA spectra to classify compounds into one of four structural groups and combines this with retention time and mass spectra/molecular weight to identify the compounds. This strategy was applied on a small amount of extract (2 mg) of Colchicum crocifolium to dereplicate 10 known compounds from four different structural groups, namely (-)-demecolcine, 2-demethyl-(-)-colchicine or 3-demethyl-(-)-colchicine, N-deacetyl-(-)-colchicine, (-)-colchiciline, (-)-colchicine, beta-lumidemecolcine, 2-demethyl-beta-lumicolchicine or 3-demethyl-beta-lumicolchicine, N,N-dimethyl-N-deacetyl-beta-lumicornigerine, (-)-isoandrocymbine and (-)-autumnaline. Furthermore, a new compound was identi?ed as N,N-dimethyl-N-deacetyl-(-)-cornigerine. Three compounds, which had molecular ions at m/z 325, 340 and 374, could not be dereplicated into any obvious structural classes that have been isolated in our laboratories previously or reported in the literature.

High-Resolution MS, MS/MS, and UV Database of Fungal Secondary Metabolites as a Dereplication Protocol for Bioactive Natural Products

“…The TIC and PDA data of the crude extract suggested a series of structurally related compounds with distinctive UV absorption patterns. ACD/ Intellixtract analysis of the UPLC-HRMS data led to the identification of five compounds, 5-methoxysterigmatocystin (11), brevianamide P (12), sterigmatocystin (13), aversin (14), and 6,8-di-O-methyl averufin (15). These assignments were confirmed by checking the HRMS and MS/MS spectra and UV absorption maxima with those in the database (Figures 5 and 6).…”

“…The ability to characterize a plant's taxonomy (at least to the genus level) based on morphology can simplify the dereplication process, as it enables botanical extracts to be screened for known chemical compounds specific to the taxa under investigation. Some examples include colchicinoids in Colchicum spp., 11 acetogenins in plants of the Annonaceae, 12 phenolics in the genus Lippia, 13 steroidal alkaloids in Buxus spp., 14 and triterpenoids in the genus Actaea. 15 In contrast, dereplication can be more complicated for organisms of unknown taxonomy.…”

From Retrospective Assessment to Prospective Decisions in Natural Product Isolation: HPLC-SPE-NMR Analysis of Carthamus oxyacantha

“…Repetitive isolation of known or even readily available natural products is one of the main factors limiting productivity of natural products research. − Dereplication, i.e., recognition and exclusion from further isolation efforts of extract constituents that have already been studied or are otherwise unwanted, is therefore a cornerstone of lead discovery programs based on natural products. − A number of techniques, mainly HPLC with mass spectrometric (HPLC-MS) or photodiode array (HPLC-PDA) detection, supported by databases are being used for early recognition of known or unwanted chemical entities in extracts. − However, natural products are best identified by NMR spectroscopy at a homogeneous stage, which normally requires a laborious fractionation and purification process. In summary, the assessment of the value of isolation efforts undertaken is traditionally retrospective in nature and as such cannot be used to make early stop-or-go decisions while the fractionation is in progress.…”

Mass spectrometric study of colchicine and its synthetic derivatives 10-alkylthiocolchicines

“…10,11 The MS methods have been used to establish fragmentation patterns of some colchicine analogues and for detection and identification of components in Colchicum species, whereas mass spectrometry with liquid chromatography, LC/ESI-MS/MS or LC-APCI-MS, have found application in detection of colchicine in sheep serum and milk and in human blood plasma. 10,[12][13][14][15][16][17][18] In the present work five 10-alkylthiocolchicine derivatives ( Figure 1) were investigated for the principal fragmentation pathways of the molecular ions using EI and protonated molecules using MALDI mass spectrometry. Colchicine was used as the reference compound and its fragmentation spectra were compared with literature data, obtained by using other methods of soft ionization.…”