Modular and scalable synthesis of nematode pheromone ascarosides: implications in eliciting plant defense response

A highly efficient and modular synthesis of nematode pheromone ascarosides was developed, which highlights a 4-step scalable synthesis of the common intermediate 10 in 23% yield from commercially available L-rhamnose by using orthoesterification/benzylation/orthoester rearrangement as the key step. Six diverse ascarosides were synthesized accordingly. Notably, biological investigations revealed that ascr#1 and ascr#18 treatment resulted in enhanced callose accumulation in Arabidopsis leaves. And ascr#18 also increased expression of defense-related genes such as PR1, PDF1.2, LOX2 and AOS, which might contribute to the enhanced plant defense responses. This study not only allows a facile access to the 1-O, 2-O, 4-O variable ascarosides, but also provides valuable insights into their bilogical activities in inducing plant defense, as well as the mode of action.