新型含七元醚环的脯氨酸衍生物的合成  

Synthesis of Novel Proline Derivatives Containing 7-Membered Ether Ring

作　　者：盛钊君[1,2] 杜志云[1] 董长治[1,2] 张焜[1] 

机构地区：[1]广东工业大学轻工化工学院天然产物及绿色化学实验室,广东广州510006 [2]法国巴黎第七大学ITODYS实验室,法国巴黎75205

出　　处：《合成化学》2014年第5期577-581,615,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21172046)

摘　　要：以L-谷氨酸和苯甲醛为起始原料,经7步反应合成了重要中间体(2S,5R)-1-苄基-5-(2-羟乙基)吡咯烷-2-羧酸叔丁酯(1),总产率19%;1经TBDMSCl保护羟基后,用10%Pd/C催化氢解去除苄基制得游离胺(2S,5R)-5-(2-二甲基叔丁基硅氧烷基乙基)吡咯烷-2-羧酸叔丁酯(3);3与Boc-β-Cl-ala,在碱性条件下偶合得氯代烃消去产物(2S,5R)-1-[(2-叔丁氧甲酰胺基)丙烯酰基]-5-(2-二甲基叔丁基硅氧烷基乙基)吡咯烷-2-羧酸叔丁酯(4),或在中性条件下偶合得(2S,5R)-1-[(R)-2-叔丁氧甲酰胺基-3-氯丙酰基]-5-(2-二甲基叔丁基硅氧烷基乙基)吡咯烷-2-羧酸叔丁酯(5);4或5经四丁基氟化铵去除TBDMS保护并发生关环反应合成了新型的七元醚环化合物(4R,7S,9R)-4-甲基-4-叔丁氧甲酰胺基-5-羰基-3-氧杂氮杂卓[1,4]并吡咯[1,2-d]-7-羧基叔丁酯(简称6);6于室温在氯仿中静置2 d^3 d自发转换为其构象异构体(4S,7S,9R)-6(简称6',6/6'=1/9),其结构经1H NMR,13C NMR,2D NMR和HR-ESI-MS表征。A key intermediate（l） with the total yield of 19% was prepared by a sven-step reaction u- sing L-glutamic acid and benzaldehyde as the starting materials. 3 was prepared by the protection of the hydroxyl followed by the removal of the benzyl by hydrogenolysis with 10% Pd/C from 1. 4 and 5 were obtained by the coupling reaction of 3 with Boc-β-Cl-ala under alkaline conditions or neutral conditions, respectively. A novel proline derivative（6） containing 7-membered ether ring was synthesized by the removal of TBDMS with tetrabutylammonium fluoride and then cyclization from 4 or 5. 6 spontaneously conversed from R conformation to S conformation in chlofform to give （4S,7S,9R）-6（6′, 6/6′ = 1/9）. The structures were characterized by 1H NMR, 13C NMR, 2D NMR and HR-ESI-MS.

关 键 词：七元醚环 非肽药物 构象异构 合成 

分 类 号：O626[理学—有机化学]