Regiospecificity of peroxyl radical addition to (E)-retinoic acid.
Regiospecificity of peroxyl radical addition to (E)-retinoic acid.
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过氧自由基与(E)-视黄酸加成的区域特异性。
DOI：
10.1021/tx970045m
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Compadre,RL
中科院分区：
文献类型：
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作者：
Samokyszyn,VM;Freyaldenhoven,MA;Chang,HC;Freeman,JP;Compadre,RL
研究了(E)-维甲酸(RA)与过氧化自由基加成反应的区域化学。在吐温20胶束中，13-羟基过氧基-(9Z，11E)-十八碳二烯酸与羟基(卟啉)铁(III)反应生成的过氧基与RA反应。主要的和几乎唯一的维甲酸氧化产物是5，6-环氧维甲酸，通过与合成环氧乙烷的共层析(在反相高效液相色谱系统中)、电子吸收光谱、高场1H-核磁共振和EI质谱学鉴定。这些结果表明，过氧基通过与C5或C6的区域选择性加成而与RA反应，分别生成内环叔烯丙基或叔碳中心自由基加合物。烷氧基随后的β消除反应生成环氧乙烷。为了对观察到的依赖于过氧基的环氧化反应的区域专一性进行了计算研究，分别使用Tripos力场参数和AM1进行了分子力学和半经验量子力学计算。结果表明，区域特异性环氧化反应可能受到取代环己烯环上的5，6-烯烃作为部分孤立双键的功能以及取代环己烯环上固有的烯丙基A1，2应变的影响。此外，计算的生成热表明，与C6相比，C5与C6发生了优先的过氧基加成反应；这可能反映了含有自由基密度的sp2-轨道的几何构型的差异，而不是高共轭多烯体系的共振贡献。
The regiochemistry of peroxyl radical addition to (E)-retinoic acid (RA) was investigated. Peroxyl radicals, generated by reaction of 13-hydroperoxy-(9Z,11E)-octadecadienoic acid with hydroxo(porphyrinato)iron(III) in Tween 20 micelles, were reacted with RA. The major, and virtually exclusive, RA oxidation product was 5,6-epoxy-RA which was identified on the basis of cochromatography with the synthetic oxirane (in a reverse phase HPLC system), electronic absorption spectroscopy, high-field1H-NMR, and EI mass spectrometry. These results suggest that peroxyl radicals react with RA by regioselective addition to either C5 or C6 yielding an endocyclic tertiary allylic or tertiary carbon-centered radical adduct, respectively. Subsequent β-elimination of an alkoxyl radical yields the oxirane. Computational studies were carried out in order to gain mechanistic insights into the observed regiospecificity of the peroxyl radical-dependent epoxidation reaction; molecular mechanics and semiempirical quantum mechanical calculations were carried out using Tripos force field parameters and AM1, respectively. The results suggest that the regiospecific epoxidation may be influenced by the 5,6-olefinic function behaving as a partially-isolated double bond as well as inherent allylic A1,2strain in the substituted cyclohexene ring as a consequence of substitutions at C1 and C6. In addition, calculated heats of formation indicated preferential peroxyl radical addition to C5 versus C6; this may reflect differences in the geometries of sp2-orbitals containing the radical densities rather than resonance contributions by the highly conjugated polyene system.