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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Versatile solid-phase synthesis of chromenes resembling classical cannabinoids
Dagmar C Kapeller1, Stefan Bräse
1Karlsruhe Institute of Technology, Campus North, ComPlat, Eggenstein-Leopoldshafen, Germany.
Abstract:
A novel solid-phase approach toward classical cannabinoids is described. The desired tricyclic natural product analogues are assembled in only four atom economic steps: domino oxa-Michael-aldol condensation, Wittig reaction/enol-ether formation, Diels-Alder cycloaddition and cleavage. The synthesis is designed to allow combinatorial chemistry at several stages of the sequence. The variation of commercially available reagents at three of the reactions (enals/enones, Wittig salts, and dienophiles) allows the introduction of various diversity points. As proof of concept, a small library of 20 members has been synthesized with overall yields ranging from 10% to 60%.
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