UMR Géoazur, Université Nice Sophia Antipolis, CNRS, IRD, Observatoire de la Côte d'Azur, 250 rue Albert Einstein, 06560, Valbonne, France.
Pharmacognosie et Chimie des Substances Naturelles, BioCIS, Université Paris-Sud, Université Paris-Saclay, CNRS, 92290, Châtenay-Malabry, France.
Angew Chem Int Ed Engl. 2019 Jan 8;58(2):520-525. doi: 10.1002/anie.201809539. Epub 2018 Dec 6.
Among the outstanding chemical diversity found in marine sponges, cyclic guanidine alkaloids, present in species of the family Crambeidae, are particularly attractive, not only because of their unique chemical features, but also due to a broad range of biological activities. Despite a growing interest in these natural products as therapeutic agents, their metabolic pathway has not been experimentally investigated. Ex situ feeding experiments using radiolabeled precursors performed on the Mediterranean sponge Crambe crambe suggest arginine and fatty acids as precursors in the metabolic pathway of crambescins. A subsequent bio-inspired approach supported the change of paradigm in the metabolic pathway of cyclic guanidine alkaloids. A large part of the chemical diversity of this family would therefore originate from a tethered Biginelli-like reaction between C-2/C-3 activated fatty acids and a central guanidinylated pyrrolinium.
在海洋海绵中发现的杰出化学多样性中，存在于 Crambeidae 科物种中的环胍啶生物碱不仅因其独特的化学特征而引人注目，而且还具有广泛的生物活性。尽管人们对这些天然产物作为治疗剂越来越感兴趣，但它们的代谢途径尚未经过实验研究。使用放射性标记前体对地中海海绵 Crambe crambe 进行的离体喂养实验表明，精氨酸和脂肪酸是 crambescins 代谢途径中的前体。随后的生物启发方法支持了环状胍啶生物碱代谢途径的范式转变。因此，该家族的大部分化学多样性都源于 C-2/C-3 激活脂肪酸与中心胍基化吡咯啉鎓之间的束缚类似 Biginelli 反应。
