生物聚合物单体2,3,4,5-O-四乙基-D-葡萄糖酸-1,6-内酯的简便合成  

Concise Synthesis of 2,3,4,5-O-Tetraethyl-D-glucono-1,6-lactone as a Monomer of Biomaterial

作　　者：焦岩[1] 方志杰[1] 姜宇华[1] 程杰[1] 郑保辉[1] 

机构地区：[1]南京理工大学化工学院,江苏南京210094

出　　处：《精细化工》2008年第6期554-557,共4页Fine Chemicals

基　　金：南京理工大学博士生培养创新基金(200705)~~

摘　　要：报道了一种生物聚合物材料的重要单体四乙基-D-葡萄糖酸-1,6-内酯的简便合成方法。室温下以工业原料D-葡萄糖酸-1,5-内酯为起始物,在三苯氯甲烷、吡啶溶液中反应得到三苯甲基保护6-羟基的葡萄糖酸内酯,后者在w(KOH)=30%的甲醇溶液中断裂内酯键,所得葡萄糖酸盐溶于二甲亚砜,0℃时加入氢化钠(12倍摩尔)、溴乙烷(11倍摩尔),25℃搅拌3 h,得6-O-三苯甲基-2,3,4,5-O-四乙基葡萄糖酸乙酯,三步收率40%,后者在V(乙酸)/V(水)=4溶液中70℃反应2 h脱去6-三苯甲基,KOH水溶液中水解除去乙酯键、w(HCl)=5%的盐酸酸化得到重要中间体D-四乙基葡萄糖酸(Ⅵ),最后经双环己基碳化二亚胺(DCC)、4-二甲氨基吡啶(4-DMAP)、4-二甲氨基吡啶盐酸盐(4-DMAP.HCl)脱水成环合成了目标化合物。对上述合成路线进行了优化,羟基的乙基保护反应中,加入过量氢化钠(23倍摩尔),反应结束后加入甲醇和水,所得强碱性溶液断裂乙酯键,产物脱去三苯甲基得到化合物(Ⅵ),实现了羟基保护和羧基脱保护一步法合成,减少了分离提纯步骤。产物结构经核磁共振表征。Firstly, protection of 6-hydroxyl of D-glucono-1 ,5-1actone was achieved by trityl chloride （TrCl） in pyridine at room temperature. Then hydrolysis of 6-O-Tr-D-glucono-1,5-1actone in 30% KOH methanol solution was conducted. To a solution of resulting gluconate in DMSO, Nail（ 12eq. ） and EtBr（ 11eq. ） were added at 0 ℃ ,and the solution was stirred for 3 h at 25 ℃. Ethyl 6-O-Tr-2,3,4,5- O-tetraethylgluconate（Ⅳa） was obtained with a total yield of 40% in 3 steps. Secondly, compound IVa was heated in aqueous acetic acid（ VHOAe/VH2O = 4 ） at 70 ℃ for 2 h to give ethyl tetraethylgluconate （ Ⅴ ）. Tetraethylgluconic acid（Ⅵ ） was prepared from hydrolysis of compound Ⅴ in KOH solution then acidified by 5% HCl. At the end, dehydration of compound Ⅵ by dicyclohexylcarbodiimide（DCC） ,4- dimethylaminopyridine（4-DMAP） and 4-dimethylaminopyridine hydrochloride（4-DMAP · HCl） gave the target compound tetraethylglucono-1 ,6-1actone. The synthesis route was optimized. In the process of ethylation,excess NaH（23eq. ） was added,and MeOH and water were dropped when the reaction was completed. Ester bond of compound Ⅳa was destroyed in alkaline solution to produce 6-O-Tr-2,3,4,5-O-tetraethylgluconic acid （ Ⅳ b ）. Deprotection of 6-OH of compound Ⅳ b furnished compound Ⅳ. Hence, a one-pot reaction containing protection of hydroxyl and deprotection of carboxyl was developed, and the purification process was also simplified. The structure of target compound was confirmed by 1^HHNMR.

关 键 词：葡萄糖酸内酯 单体 生物材料 

分 类 号：O629.11[理学—有机化学]