合成路线1

A synthesis for optically pure (-)-huperzine A, through modification of the previously reported synthesis of (±)-huperzine A, has been described: Intermediate methyl ester (XI) of this synthesis [Drugs Fut 1990, 15(6): 616] is transesterified with (-)-8-phenylmenthol (A) in refluxing benzene to give the optical ester (XIa), suitable for a stereocontrolled cyclization. The cyclization of (XIa) with 2-methylacrolein, as in the previous synthesis, yields the tricyclic compound (XIIa) [an analogue of the previously reported (XII), but with the adequate absolute configuration]. The following step is dehydration to (XIVa), in the same way as in the case of (XIV) of the previous synthesis. From here, the previously reported synthetic route is repeated, finally yielding optically pure (-)-huperzine A. In some steps, separation of undesirable minor amounts of other enantiomers must be performed.