Studies towards the total synthesis of solanoeclepin A: synthesis and potato cyst nematode hatching activity of analogues containing the tetracyclic left-hand substructure

Abstract

In our studies towards the total synthesis of solanoeclepin A, a natural hatching agent of potato cyst nematodes, three analogues containing the tetracyclic left-handed substructure have been synthesised. First, the synthesis of the parent tetracycle 2 in enantiopure form is reported. Key steps are (1) chromium-mediated coupling of aldehyde 5 (see preceding paper in this issue) and vinyl triflate 6 to furnish an α,β-unsaturated lactone, which was transformed into triene 4 in six-steps, (2) ring-closing metathesis of 4 to tetracycle 3 and (3) oxidative functionalisation of the least substituted double bond of 3 to provide the fully functionalised tetracyclic left-handed substructure of solanoeclepin A. The methodology developed was successfully applied in the synthesis of two more elaborate solanoeclepin A analogues 9 and 11. Both compounds, prepared as mixtures of diastereomers, showed promising biological activity in hatching activity tests.