Identification of Photocatalytic Alkaloids from Coptidis Rhizome by an Offline HPLC/CC/SCD Approach

Abstract

Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.

A box-in-box supramolecular assembly for the highly selective recognition of natural, epigenetically and chemically modified cytosines in water

“…With the Tyndall effect and UV appearance in hand, we tried to use NMR 27,28 to probe the host and guest interactions in solution by detecting the chemical shift changes of protons on both 1 and SC4H. At pH = 7, like the weak non-covalent interactions in GNPS 29 and GBPS, 30 and the electrostatic interactions in a tetraphenylethene system, 31 the chemical shift of the peaks ascribed to 1 (Ha, Hb, Hc, Hd, He, Hf and Hg) showed marginal changes [up-field shifts of 0.02, 0.01, 0.01, 0.04, 0.01, 0.02 and 0.02 ppm (Fig.…”