| Affiliation: | 1. Chimie des Substances Naturelles, BioCIS, Université Paris-Saclay, CNRS, 92290 Châtenay-Malabry, France;2. Laboratoire de Chimie-Toxicologie Analytique et Cellulaire (C-TAC), UMR CNRS 8038 CiTCoM, Université de Paris, 4, Avenue de l'Observatoire, 75006 Paris, France Laboratoire Écologie, Évolution, Interactions des, Systèmes Amazoniens (LEEISA), USR 3456, Université de Guyane, CNRS Guyane, 275, route de Montabo, 97334 Cayenne, French Guiana;3. Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1, avenue de la Terrasse, 91198 Gif-sur-Yvette, France |
| Abstract: | Camellimidazoles A–C were recently reported as natural substances in Keemun black tea. Although a “biosynthetic” route to these intriguing imidazole dimers was proposed from caffeine by the authors in this seminal report, we envisioned that a artefactual scenario, consisting of alkaline hydrolysis of caffeine and spontaneous cascade reactions with a methylene donor such as formaldehyde or methylene chloride, could also have led to their formation. To capture the diversity of molecules obtained under these conditions (i.e. alkaline treatment of caffeine/formaldehyde), an in silico MetWork-based pipeline was implemented, highlighting the sought-after camellimidazoles B and C. A wealth of further compounds were also tagged, notably comprising the herein newly described and unnatural camellimidazoles D –F that were subsequently confirmed as anticipated in silico upon extensive spectroscopic analyses. Likewise, camellimidazoles B and C could also be obtained using methylene chloride as an alternative methylene donor which may also have occurred in the initial phytochemical pipeline that implied this solvent. The current investigation emphasizes the fitness of MetWork tagging to extend the logic of in silico anticipation of metabolic pathways to organic chemistry reactions. |
