Jorg C. J. Benningshof

Synthesis of the Right‐Hand Substructure of Solanoeclepin A

A synthesis of the right-hand substructure 7 of solanoeclepin A (1), the most active natural hatching agent of potatocyst nematodes, was approached by an intramolecular [2+2] photocycloaddition. The construction of the strained bicyclo[2.1.1]hexane skeleton was achieved in five steps from dioxenone 9. A Simmons−Smith cyclopropanation enabled the installation of the required cyclopropane. Finally, a TPAP oxidation allowed the smooth formation of the strained cyclobutanone moiety.

Studies towards the total synthesis of solanoeclepin A: synthesis and potato cyst nematode hatching activity of analogues containing the tetracyclic left-hand substructureElectronic supplementary information (ESI) available: further experimental details. See http://www.rsc.org/suppdata/p1/b2/b202020n/

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.

Studies towards the total synthesis of solanoeclepin A: synthesis of the 7-oxabicyclo[2.2.1]heptane moiety and attempted seven-membered ring formation

This paper details studies towards the total synthesis of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes. The first goal was the preparation of the tetracyclic left-handed substructure 2 in enantiopure form. The 7-oxabicyclo[2.2.1]heptane moiety was obtained via a diastereoselective intramolecular Diels–Alder strategy by using (R)-phenylglycinol as a chiral auxiliary as pioneered by Mukaiyama. A chromium-mediated nickel-catalysed coupling of aldehyde 5 with vinyl triflate 6 gave α,β-unsaturated lactone 18 as a single stereoisomer. The seven-membered ring was expected to arise from a McMurry coupling of dialdehyde 4. Surprisingly, oxidation of diol 24 did not lead to the desired dialdehyde 4, but to the eight-membered ring lactone 25.

Intramolecular [2+2] photocycloadditions as an approach towards the bicyclo[2.1.1]hexane substructure of solanoeclepin A

The synthesis of a tricyclic substructure of solanoeclepin A is described. The key step involves an intramolecular [2+2] photocycloaddition between a dioxinone and a tetrasubstituted bicyclic alkene providing the strained bicyclo[2.1.1]hexane moiety.

Intramolecular [2+2] photocycloadditions as an approach towards the right-hand side of solanoeclepin A

A racemic synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes, was approached via an intramolecular [2+2] photocycloaddition of 6-unsubstituted dioxenones with variously substituted pendent alkenes. The synthesis of the cyclisation precursors involved a very efficient iodide–magnesium exchange reaction with iododioxenone 6, which allowed facile allylation at C-5 of the dioxenone. Photochemistry with dioxenones 12 and 17 led to novel bicyclo[2.2.0]hexanes 24 and 26. The use of the more rigid lactone precursor 14 led to bicyclo[2.1.1]hexane 25, and allowed the stereoselective synthesis of the complex tricyclic core of solanoeclepin A. The structure of 25 was unequivocally proven by X-ray crystal structure determination.

Enantioselective synthesis of the tetracyclic left-hand substructure of solanoeclepin A

The synthesis of the enantiopure left-hand substructure of solanoeclepin A is described. Key steps include a chromium-mediated coupling of an oxabicyclic aldehyde with a β-ketoester-derived enol triflate to give a lactone, and a ring-closing metathesis reaction to form the seven-membered ring.