(1S，5R，6R，7R)-6-羟甲基-7-羟基-2-氧杂双环[3．3．0]辛-3-酮的合成  

Synthesis of(1S,5R,6R,7R)-6-Hydroxymethyl-7-hydroxy-2-oxabicyclooctan-3-one

作　　者：冯泽旺[1] 赵信岐[1] 孙成辉[1] 毕华[2] 

机构地区：[1]北京理工大学材料科学与工程学院,北京100081 [2]北京华禧联合科技发展有限公司,北京102206

出　　处：《精细化工》2008年第7期715-719,共5页Fine Chemicals

摘　　要：（1S，5R，6R，7R）-6-羟甲基-7-羟基-2-氧杂双环[3．3．0]辛-3-酮（Ⅵ）是制备前列腺素的关键中间体。为了简化工艺条件，降低生产成本，以环戊二烯和二氯乙酰氯为原料，经环加成、还原和Baeyer．Villiger氧化3步反应制得2-氧杂双环[3．3．0]辛-6-烯-3-酮（Ⅳ），收率83．9％；经光学拆分后，与多聚甲醛经区域选择性Prins反应、粗产品不经分离，直接水解合成了Ⅵ，总收率22．0％。讨论了拆分剂、结晶溶剂对拆分Ⅳ的作用，确定了以R-（＋）-苯乙胺为拆分剂，乙酸乙酯为结晶溶剂来拆分Ⅳ，拆分收率34．3％，[α]D^20=-104．0°（c=1．0，MeOH），熔点：42～46℃。对Prins反应后水解产物的后处理工艺进行了优化，用氯仿重结晶代替柱分离来精制产品，收率76．5％，[α]2D^20=-45．0°（c=1．0，MeOH），熔点：117～119℃。目标产物用IR、MS、^1H NMR进行了表征。（ 1 S, 5 R, 6R, 7 R） -6-Hydroxymethyl-7 -hydroxy-2-oxabicyclo [ 3.3.0 ] octan-3 -one （Ⅵ） is an intermediate for preparing prostaglandins. In order to simplify the technological process and reduce production costs, racemic 2-oxabicyclo [ 3.3.0 ] octa-6-en-3-one （ Ⅳ ） was prepared in 83.9% yield from cyclopentadiene and dichloroacetyl chloride through a process of cycloaddition, reduction and Baeyer-Villiger oxidation, and Ⅵ was obtained through optical resolution of Ⅳ and regioseletive Prins reaction with polyformaldehyde followed by hydrolysis of the product without separation. The overall yield was 22.0%. The effect of optically active resolving reagents and solvents for crystallization on resolving Ⅳ was discussed. Using R-（ ＋ ） -phenylethylamine as the resolving reagent and ethyl acetate as the solvent for crystallization,optical Ⅳ was obtained in 34.3% yield, [ α]D^20 =-104.0° （ c = 1.0, MeOH）, m. p. 42 - 46℃ . The work-up process of the product after Prins reaction and hydrolysis was improved by recrystallizing the product from chloroform instead of column separation;the yield of the product was 76.5%, [α]D^20 = -45.0°（c = 1.0,MeOH）,m. p. 117 - 119 ℃. The product was confirmed by IR,MS and ^1H NMR.

关 键 词：Corey内酯 中间体 前列腺素 拆分 医药原料 

分 类 号：R914.5[医药卫生—药物化学]