Synthesis of Methyl Oxazole and Oxazole,Intermediates of Leucamide A

OxazoleⅠand methyl oxazoleⅡ,key intermediates of leucamide A which is a natural ocean material,were prepared from L-serine,L-alanine and L-threonine by two different methods.L-Serine was esterified,followed by coupling with L-alanine protected with tert-butoxycarbonyl(Boc) group to give dipeptide Ⅴ.In this reaction N,N′-dicyclohexylcarbodiimide(DCC) was uesed as coupling reagent,1-hydroxybenzotriazole as auxiliary and triethylamine as base.Cyclodehydration of Ⅴ was accomplised with Burgess reagent to give Ⅵ.OxazoleⅠwas obtained after oxidation of Ⅵ with bromotrichloromethane in the presence of 1,8-diazabicycloundec-7-ene(DBU) in a total yield of 47.8%.Methyl oxazole Ⅱ was prepared from L-serine and L-threonine.After methyl esterification and protection with(Boc)_2O,the derivate of L-serine was treated with 2,2-dimethoxypropane,followed by saponification to afford Garner acid Ⅸ.Then Ⅸ was coupled with L-threonine methyl ester to give dipeptide Ⅺ.Ⅺ was oxidated with Dess-Martin periodinane,followed by cyclization in the presence of triphenylphosphine and iodine to furnish methyl oxazoleⅡin a total yield of 46.1%.Structures of the targets and intermediates are confirmed by NMR.