合成路线1

The previously reported open-chain styrene intermediate (I) is submitted to a Sharpless asymmetric epoxidation to give, after chromatographic purification, the diol (II), which is cyclized by means of TFA and 2-hydroxypyridine yielding the macrocycle (III). The reaction of (III) with trimethyl orthoformate and pyridinium p-toluenesulfonate (PPTS) in dichloromethane affords the cyclic orthoester (IV), which is treated with trimethylsilyl iodide to provide the iodo formate (V). Finally, this compound is converted into the target macrocyclic epoxide by treatment with K2CO3 in methanol/THF. Alternatively, the intermediate cyclic orthoester (IV) can be treated with acetyl bromide to give the bromo formate (VI), which is converted into the target epoxide by reaction with K2CO3 as before.