Structural characterization of adducts formed in the reaction of 2,3-epoxy-4-hydroxynonanal with deoxyguanosine.
Structural characterization of adducts formed in the reaction of 2,3-epoxy-4-hydroxynonanal with deoxyguanosine.
复制标题
2,3-环氧-4-羟基壬醛与脱氧鸟苷反应形成的加合物的结构表征。
DOI：
10.1021/tx00007a004
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发表时间：
1989
影响因子：
4.1
通讯作者：
Chung,FL
中科院分区：
文献类型：
--
作者：
Sodum,RS;Chung,FL
用反相高效液相色谱法从脱氧鸟苷与反式-4-羟基-2-壬烯醛的环氧化物反应中分离出六种加合物。这些加合物被设计为加合物1-6。通过紫外光谱、核磁共振氢谱、质谱、CD等光谱方法和化学反应对这些加合物的结构进行了表征。加合物1先前被鉴定为l^-乙烯脱氧鸟苷。加合物2、3、5和6是在鸟嘌呤的1-和N2-位具有两个五元稠合环的四种非对映异构体1 ^-乙醇脱氧鸟苷衍生物。这些加合物的系统名称为3-（2-脱氧-β-D-异丙基-戊呋喃糖基）-3，5，5a，7，8，8a-六氢-8-羟基-7-戊基-10H-呋喃并[2，3，4，5]咪唑并[1，2-o]-嘌呤-10-酮。加合物5和6的酸水解产生相应的鸟嘌呤产物，它们在所有方面都是相同的，除了具有相反的CD。加合物2和3得到类似的结果，表明它们是两对映体。阐明了这些加合物的立体化学特征。加合物4通过光谱方法和化学反应表征为3-（2-脱氧-β-D-赤藓糖基-戊呋喃糖基）-5，9-二氢-7-（1，2-二羟基庚基）-9，1’-咪唑并[1，2-a]嘌呤-9-酮，一种1，1’-乙烯脱氧鸟苷衍生物。在温和的碱处理后，加合物2、3、5和6容易地转化为加合物1。这些加合物的形成和加合物2，3，5，和6加合物1的转化的机制进行了讨论。
Six adducts were isolated by reverse-phase high-performance liquid chromatography from the reaction of deoxyguanosine at 50 C inpH 7.0 buffer with the epoxide of irans-4-hydroxy-2-nonenal, a major, ß-unsaturated aldehyde from lipid peroxidation. These adducts were des-ignated as adducts 1-6. Structuresof these adducts were fully characterized by spectroscopic methods such as UV, proton NMR, MS, and CDand by chemical reactions. Adduct 1 was previously identified as l^-ethenodeoxyguanosine. Adducts 2, 3, 5, and 6 are four diastereomeric l^-ethanodeoxyguanosine derivatives possessing two five-membered fused rings at the 1-and N2-positions of guanine. The systematic name of these adducts is 3-(2-deoxy-/3-D-erythro-pentofuranosyl)-3, 5, 5a, 7, 8, 8a-hexahydro-8-hydroxy-7-pentyl-10H-furo [2,, 3,: 4, 5] imidazo [l, 2-o]-purin-10-one. Acid hydrolysisof adducts 5 and 6 yielded the corresponding guanine products which were identical in all respects except having opposite CD. Similar results were obtained with adducts 2 and 3, suggesting they are two pairs of enantiomers. The stereochemical characteristics of these adducts were elucidated. Adduct 4 was characterized by spectroscopic methods and chemical reactions as 3-(2-deoxy-/3-D-eryfhro-pentofuranosyl)-5, 9-dihydro-7-(l, 2-dihydroxyheptyl)-9íf-imidazo [l, 2-a] purin-9-one, a 1 A^-ethenodeoxyguanosine derivative. Upon mild base treatment, adducts 2, 3, 5, and 6 were readily converted to adduct 1. The mechanisms for the formation of these adducts and the conversion of adducts 2, 3, 5, and 6 to adduct 1 are discussed.