合成路线1

The precursor amino alcohol (XXVIII) was prepared by the following synthetic routes. Claisen orthoester rearrangement of (-)-myrtenol (XXIII) with triethyl orthoacetate at 165-195 C afforded the gamma,delta-unsaturated ester (XXIV). Subsequent ozonolysis of the exocyclic double bond gave rise to keto ester (XXV). Alternatively, keto ester (XXV) was obtained as the major diastereoisomer by alkylation of the lithium enolate of (R)-(+)-nopinone (XXVI) with ethyl bromoacetate in the presence of 1,3-dimethyl-2-imidazolidinone (DMI). Ketone (XXV) was either converted to oxime (XXVI) or to O-methyl oxime (XXVII) by treatment with hydroxylamine or O-methyl hydroxylamine, respectively. Reduction of the hydroxyimino and ester groups of (XXVI) to the key amino alcohol intermediate (XXVIII) was performed by using the combination LiAlH4/AlCl3 or with NaBH4 in the presence of several Lewis acids. The O-methyl oxime (XXVII) was directly reduced to amino alcohol (XXVIII) employing NaBH4 in the presence of boron trifluoride etherate or AlCl3 or, alternatively, with sodium metal in n-propanol. Optionally, the oxime ester (XXVII) was converted to (XXVIII) in a two step procedure, by first reduction of the ester group to alcohol (XXIX) with sodium bis(2-methoxyethoxy)aluminium hydride, and then reduction of the O-methyl oxime with sodium in n-propanol.