合成路线1

The Stille coupling of the benzodioxanone (XII) with allyltributyltin (XIII) by means of trifurylphosphine (TFP) and Pd2(dba)3 gives the 6-allylsalicylic acid (XIV), which is esterified with the intermediate (XI) by means of DEAD and PPH3 in ethyl ether to yield the ester (XV). Hydrolysis of the lactol group of (XV) with Ac-OH affords the carbaldehyde (XVI), which is condensed with the phosphorane (XVII) to provide the unsaturated ester (XVIII). The silylation of the free OH groups of (XVIII) with Tbdms-OTf and lutidine gives the protected compound (XIX), which is submitted to a rig closing metathesis reaction catalyzed by a Ru catalyst in dichloromethane to yield the macrolactone (XX). The selective hydrolysis of the methyl ester group of (XX) by treatment with (Bu3Sn)2O in refluxing toluene affords the unsaturated carboxylic acid (XXI), which is treated with DPPA in refluxing benzene to provide the corresponding isocyanate (XXII). The reaction of the isocyanate group of (XXII) with (1Z,3Z)-hexadienyl cuprate, prepared in situ by reaction of Et-Li, CuBr/Me2S and acetylene, gives the silylated heptadienamide (XXIII), along with some pentanamide and nonatrienamide derivatives that are separated by chromatography. Finally, compound (XXIII) is desilylated by means of HF and pyridine in THF to provide the target salicylhalamide A.