Total Synthesis Of N-Octyl-?-Valienamine(NOV)and N-Octyl-4-Epi-?-Valienamine(NOEV)from(-)-shikimic Acid

N-Octyl-?-Valienamine(NOV)and N-Octyl-4-Epi-(3-Valienamine(NOEV)have potential therapeutic effect on Gaucher disease and GM1 gangliosidosis respectively.Therefore,it is of condiderable significance to develop new synthetic routes to these two compounds.Herein a common synthetic route to NOV and NOEV starting from(-)-shikimic acid was described.The synthetic route for NOV is as follows:Firstly,(-)-shikimic acid was esterified to give ethyl shikimate ?-2 in 97%yield.Compound ?-3 was smoothly synthesized via Vilsmier-Haauce reactions of compound ?-2 in 91%yield.When compound ?-3 was treated with K2CO3,3,4-epoxy compound ?-4 could be succesfully obtained in 95%yield after deblocking and intemolecular substitution.Methanesulfonylation of epoxide ?-4 gave compound ?-5,which then underwent ring-opening in boiled H2O to give compound ?-6 in 96%yield.Compound ?-6 was treated with sodium azide in the presence of 2 equivalent of Et3N by using ethanol as the solvent,compound ?-7 was obtained in 84%yield after epoxide-formation.Reduction of compound ?-7 with DIBAL-H then be treated with benzoyl chloride to give compound?-8 in 90%yield.Ru-catalyzed asymmetric dihydroxylation of compound ?-8 occurred smoothly to afford compound ?-9 in 92%yield.Compound ?-9 was esterified to give compound ?-10,then intramolecular ?-elimination took place to afford compound ?-11 in 83%yield.The one-pot procedure via Staudinger reaction,Wittig reaction and imine reduction could then afford compound ?-12 in 82%yield.Finally,the desired compound NOV was obtained in 90%yield after removal of all the protecting groups.The synthetic route for NOEV is as follows:Compound ?-9 was treated with acetic anhydride in the presence of Et3N to afford compound ?-13 in yield,then intramolecular ?-elimination took place to afford compound ?-14 in 83%yield.Selective deprotection of acetyl group with P-TsOH provided compound ?-15 in 80%yield.Methanesulfonylation of compound?-15 gave compound 111-16,which then underwent SN2 reaction in Et3N-R'COOH to give compound ?-17 in 76%yield.Finally,the desired compound NOEV was obtained in 73%yield from compound 111-17 through the same steps of NOV from compound ?-11.