Dereplication strategies in natural product research: How many tools and methodologies behind the same concept?

Abstract

The development of new drugs will certainly benefit from an ever improving knowledge of the living beings chemistry. However, identification of drugable molecules within the immense biodiversity of forests, soils or oceans still requires considerable investments in technical equipments, time and human resources. An important part of this process is the quick identification of known substances in order to concentrate the efforts on the discovery of new ones. A range of "dereplication" procedures are currently emerging to meet this challenge as key strategies to improve the performance of natural product screening programs. Initially defined in 1990 as "a process of quickly identifying known chemotypes", dereplication is today a not so univocal concept and has evolved over the last years in different ways. The present review covers all dereplication-related sudies in natural product research from 1990 to 2014.Its writing brought to light five distinct dereplication workflows that can be characterized by the nature of starting materials, by the key analytical technique, and above all by the final objective. Dereplication can be used as an untargeted workflow for the rapid identification of the major compounds whatever their chemical class in a single sample or for the acceleration of bioactivity-guided fractionation procedures. In other cases dereplication is fully integrated in metabolomic studies for the untargeted chemical profiling of natural extract collections or for the targeted identification of a predetermined class of metabolites. Finally a quite distinct dereplication approach mainly based on gene-sequence analyses is frequently used for the taxonomic identification of microbial strains.

Identification of Alkaloids from Hippeastrum aulicum (Ker Gawl.) Herb. (Amaryllidaceae) Using CGC-MS and Ambient Ionization Mass Spectrometry (PS‑MS and LS-MS)

“…After analytical TLC analysis, fractions were again combined by similarity, yielding 12 subfractions. Sample 9.8.7 was purified by SPTLC (EtOAc:CH 2 Cl 2 :Me 2 CO:MeOH:n-Hex, 2:2:2:1:1, along with drops of NH 4 OH, in NH 3 atmosphere) allowing the purification of the alkaloids haemanthidine (22) and 6-epihaemanthidine (23) (16.5 mg).…”

“…These fractions were analyzed by TLC and then combined according to their alkaloidal profile under UV λ 254 light and Dragendorff's reactive spots, affording 18 fractions. Fraction 9 (60.0 mg) was purified by SPTLC (CH 2 Cl 2 :EtOAc:Me 2 CO:n-Hex:MeOH, 2:2:1.5:3:1, along with drops of NH 4 OH, in NH 3 atmosphere) and alkaloids haemanthamine (16) (6.5 mg), albomacuine (29) (3.5 mg) and 7-methoxy-O-methyllycorenine (12) (8.0 mg) were isolated. The alkaloid aulicine (15) (48.0 mg) precipitated from fraction 11.…”

“…The fractions were combined according to their alkaloid profile by TLC using UV (λ 256) and Dragendorff's reagent stain, resulting in 11 subfractions. SPTLC (EtOAc:CH 2 Cl 2 :Me 2 CO:MeOH:n-Hex, 2:2:1:1:1, along with drops of the NH 4 OH, in NH 3 atmosphere) was performed to purify subfraction 13.6, and the alkaloid galanthine (21) (3.6 mg) was isolated. Subfraction 13.7 was identified as the alkaloid haemanthamine (16) (49.0 mg).…”

“…The specific EI-MS fragmentation mechanisms for the distinct skeleton types together with retention indices are the key for alkaloid identification in Amaryllidaceae research. Concerning the skeleton types found in H. aulicum, the EI mass fragmentation of homolycorine-type alkaloid D 3,4 -derivatives features a dominant retro-Diels Alder process and cleavage of ring C, yielding a very abundant ion peak characterized by the pyrrolidine ring (m/z 109). 33 Consequently, the alkaloids 9, 10, 12, 27, 29 and 30 show the base peak at m/z 109 (100%), with all remaining ion peaks displaying less than 10% of abundance.…”

“…1 The current investigation on Amaryllidaceae alkaloids has focused on hyphenated techniques, which exploit the advantages of both chromatographic and spectral methods. 2,3 This strategy can be understood as a kind of dereplication process, 4 which is very attractive in that it avoids labor-intensive chromatographic steps and analysis of worthless components. Capillary gas chromatography-mass spectrometry (CGC-MS) has become the most successful technique for a dereplication approach to Amaryllidaceae alkaloids since these compounds have shown accurate detection under CGC-MS conditions.…”