Abstract
The paper illustrates two efficient routes to macrolactone 19 containing a 3โ(paraโmethoxybenzyloxy)propyl side chain at Cโ15. The chiral center at Cโ15 was introduced by a Noyori reduction of keto ester 5. The intermediate common to both routes, aldehyde 8, was prepared from keto ester 5. The subsequent chain extension utilized Evans aldol reactions. The first route leads to the alkene 14, which was used, after hydroboration, for a Suzuki crossโcoupling reaction with vinyl iodide 15. The derived seco acid 18 was converted into the macrolactone 19 by a Mitsunobu lactonization by using immobilized triphenylphosphine. Alternatively, an aldol reaction of 8 with the 4โpentenoyl derivative 20 was used to prepare alkene 26. This building block led to ester 28, which could also be converted into macrolactone 19 by the classical ringโclosing metathesis. After conversion of the Cโ15 side chain to the corresponding aldehyde, the enamide was introduced through hemiaminal formation and formal elimination of water. Separation of the doubleโbond isomers and removal of the silyl protecting groups provided salicylihalamides A (E)โ1 and B (Z)โ1.