合成路线1

Asymmetric allylation of 3-iodomethacrolein (VII) with (+)-allyldiisopinocampheyl borane at -100 C provided the enantiopure alcohol (IX). Subsequent coupling of (IX) with the diastereomeric mixture of (6R,7S) and (6S,7R)-acids (X) using DCC and DMAP afforded a mixture of diastereomeric esters from which the required (6R,7S)-isomer (XI) was isolated by flash chromatography. Ring closure by means of olefin methatesis in the presence of a ruthenium initiator gave a separable mixture of E (XII) and Z (XIII) macrolactones. Subsequent desilylation of the desired Z isomer (XIII) with HF.Pyr in THF provided the macrocyclic diol (XIV). Introduction of the thiazole unit in (XIV) was carried out by Stille coupling of vinyl iodide (XIV) with thiazolyl stannane (VI) in the presence of Pd catalyst to provide (XV). Finally, epoxidation of (XV) with methylperoxycarboximidic acid, generated in situ from hydrogen peroxide and acetonitrile, furnished the title compound.