Leucam ide A中间体——甲基口恶唑及口恶唑的合成  

Synthesis of Methyl Oxazole and Oxazole,Intermediates of Leucamide A

作　　者：陈宏亮[1] 冯亚青[1] 刘新刚[1] 孟舒献[1] 

机构地区：[1]天津大学化工学院,天津300072

出　　处：《精细化工》2006年第2期198-201,共4页Fine Chemicals

基　　金：天津市自然科学基金资助(043610611)~~

摘　　要：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。Oxazole Ⅰ and methyl oxazole Ⅱ, 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. Oxazole I was obtained after oxidation of Ⅵ with bromotrichloromethane in the presence of 1,8-diazabicyclo [ 5.4.0 ] undec-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 oxazole Ⅱ in a total yield of 46. 1%. Structures of the targets and intermediates are confirmed by NMR.

关 键 词：Leucamide A 甲基噁唑 噁唑 

分 类 号：TQ031.2[化学工程]