Stereoselective synthesis of a fully protected C 13–C 23 fragment of tedanolide

Abstract

The combination of a high-yielding dienyllithium addition and a highly diastereoselective 1,2-reduction allows the preparation of the completely protected C 13–C 23 fragment 3 of the potent cytotoxic agent tedanolide 1. A convergent approach was used, namely a late stage coupling of the dienyllithium 16 with the selectively protected aldehyde 5 followed by oxidation–reduction and final epoxidation to give 3. The dienylstannane 4 was prepared from the dibromide 6 in five steps, the key step being the highly regio- and stereoselective stannylcupration of the alkyne 7. The commercially available hydroxy ester 10 was converted in 11 steps to the aldehyde 5. The compound 3 could potentially be a key intermediate for the synthesis of tedanolide 1.