合成路线1

In an alternative synthesis, which does not utilize the alkaloid catharanthine, Sharpless asymmetric epoxidation of 2-ethyl-2-propenol (I) in the presence of ( )-diethyl tartrate provides (R)-2-ethyl-2,3-epoxypropanol (II). Subsequent addition of allylmagnesium chloride (III) to epoxide (II) leads to diol (IV), which is further protected as the corresponding acetonide (V) with 2,2 dimethoxypropane and p-TsOH. Ozonolysis of the terminal olefin (V) gives rise to aldehyde (VI). Condensation of aldehyde (VI) with the indoloazapine (VII) furnishes the bridged azepine (VIII) as a diastereomeric mixture. Without isolation, this mixture of amines is N-alkylated with benzyl bromide, and the resultant ammonium salts (IX) are subjected to rearrangement in boiling MeOH in the presence of Et3N to provide an equimolecular mixture of the tetracyclic diastereoisomers (X) and (XI) (5).