Colchicinoids from Colchicum crocifolium Boiss.: A case study in dereplication strategies for (-)-Colchicine and related analogs 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 or3-demethyl-(−)-colchicine, N-deacetyl-(−)-colchicine, (−)-colchiciline, (−)colchicine, β-lumidemecolcine, 2-demethyl-β-lumicolchicine or 3-demethyl-βlumicolchicine, N,N-dimethyl-N-deacetyl-β-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.

Recent developments in qualitative and quantitative analysis of phytochemical constituents and their metabolites using liquid chromatography–mass spectrometry

“…Typical examples of dereplication strategies for LC-MS analysis of alkaloids are colchicinoids [102], pyrrolizidine alkaloids and their corresponding N-oxides [103], aconitum alkaloids [104] and alkaloids in Catharanthus roseus roots [105]. Based on the combination of retention time, UV and mass spectra, known compounds were rapidly dereplicated and new structures were identified.…”

Colchicinoids fromColchicum crocifoliumBoiss. (Colchicaceae)

“…Moreover, the presence of new compounds was also suggested, particularly one that was proposed to be N,N-dimethyl-N-deacetyl-(À)-cornigerine (Alali et al, 2008). Those findings stimulated the present investigation, which was aimed at isolating cytotoxic components in C. crocifolium, both to have a larger amount of material R 1 =H, R 2 =COCH 3 , R 3 =CH 3 R 1 =H, R 2 =CH 3 , R 3 =CH 3 R 1 =CH 3 , R 2 =CH 3 , R 3 =CH 3 R 1 =CH 3 , R 2 =CH 3 , R 3 =H 5 Figure 1.…”

“…As part of our studies on the unique and under explored biodiversity of the Hashemite Kingdom of Jordan (Jordan) (Alali et al, 2005(Alali et al, 2006a(Alali et al, , 2006bAlali, Gharaibeh, Ghawanmeh, Tawaha, & Oberlies, 2008;Al-Mahmoud, Alali, Tawaha, & Qasaymeh, 2006), the colchicinoids of Colchicum crocifolium Boiss. (Colchicaceae) were pursued.…”

“…Colchicum crocifolium grows wildly in Jordan in clayey sandy desert, is a delicate, perennial herb, with corms covered by thick, dark-brown to reddish scales and is found flowering from March to April (AlEisawi, 1998). In preliminary studies where C. crocifolium was used as a model organism to demonstrate the feasibility and value of an LC-MS and LC-PDA system to dereplicate colchicinoids (Alali et al, 2008), 10 known alkaloids were dereplicated in addition to a *Corresponding author. Email: falali@just.edu.jo new compound, which was proposed to be N,N-dimethyl-N-deacetyl-(À)-cornigerine (Alali et al, 2008).…”

“…In preliminary studies where C. crocifolium was used as a model organism to demonstrate the feasibility and value of an LC-MS and LC-PDA system to dereplicate colchicinoids (Alali et al, 2008), 10 known alkaloids were dereplicated in addition to a *Corresponding author. Email: falali@just.edu.jo new compound, which was proposed to be N,N-dimethyl-N-deacetyl-(À)-cornigerine (Alali et al, 2008). Those promising results stimulated our research team to conduct a full phytochemical characterisation of the active components in C. crocifolium, which to the best of our knowledge had not been studied previously.…”