合成路线1

N-Demethylation of cocaine (I) is accomplished by treatment with 1-chloroethyl chloroformate, followed by methanolysis of the intermediate chloroethyl carbamate. The resultant nor-cocaine (II) is alkylated with propargyl bromide (III) to afford (IV). Acidic ester hydrolysis of (IV) furnishes hydroxy acid (V). Chlorination of (V) with POCl3, followed by treatment with methanol gives rise to the unsaturated ester (VI). Radical cyclization of the enyne system (VI) in the presence of Bu3SnH and AIBN affords a Z/E mixture of tricyclic vinyl stannanes (VIIa-b) that are separated by column chromatography. The major Z isomer is then subjected to Stille coupling with the aryl iodide (VIII), yielding adduct (IX). Then, reduction of the ester function of (IX) to the primary alcohol (X) is performed by means of either LiAlH4 or DIBAL.