Leucam ide A中间体——甲基口恶唑及口恶唑的合成

以L-丝氨酸、L-丙氨酸和L-苏氨酸为起始原料,采用两种不同的方法分别合成了天然海洋化合物Leucam ide A的关键中间体口恶唑化合物Ⅰ及甲基口恶唑化合物Ⅱ。甲酯保护的L-丝氨酸和叔丁氧羰基保护的L-丙氨酸为原料,以N,N′-二环己基碳二亚胺(DCC)为缩合试剂,1-羟基苯并三氮唑(HOB t)为助剂,三乙胺为碱,缩合得到二肽后,利用Burgess试剂关环成口恶唑啉,再以1,8-二氮杂二环5.4.0]十一烷-7-烯(DBU)和B rCC l3进行氧化脱氢,得到口恶唑化合物Ⅰ,收率为47.8%。甲基口恶唑化合物Ⅱ是以L-丝胺酸和L-苏氨酸为起始化合物。L-丝胺酸经甲酯化,叔丁氧羰基保护氨基后,以2,2-二甲氧基丙烷进行羟基和氨基的双保护,脱甲酯得到Garner酸,再与甲酯保护的L-苏氨酸缩合得到二肽。利用Dess-M artin Period inane试剂氧化其中的仲羟基,以三苯基膦和碘为试剂关环得到甲基口恶唑Ⅱ,反应收率46.1%。目标化合物及中间体结构经NMR进行了鉴定。

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.