Absolute Stereochemistry of a 4a-Hydroxyriboflavin Analogue of the Key Intermediate of the FAD-Monooxygenase Cycle
Absolute Stereochemistry of a 4a-Hydroxyriboflavin Analogue of the Key Intermediate of the FAD-Monooxygenase Cycle
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DOI：
10.1002/chem.201304393
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发表时间：
2014-04-07
影响因子：
4.3
通讯作者：
Berova, Nina
中科院分区：
文献类型：
--
作者：
Iwahana, Soichiro;Iida, Hiroki;Berova, Nina
黄素酶（如含黄素腺嘌呤二核苷酸（FAD）的单加氧酶）的生物学作用涉及氧化黄素衍生物（如4 α-氢过氧黄素和4 α-羟基黄素）的形成，其中在酶促反应期间在4 α位置处产生新的手性中心。到目前为止，在天然4 α-氧化黄素手性中心的绝对配置仍然未知，尽管它的黄素酶的多种功能的关键重要性。本文报道了3-苄基-5-乙基-10-（四乙酰基-D-核糖基）黄鎓（1）的4 α-羟基加合物3，该加合物是有机催化氧化硫化物生成亚砜的关键中间体之一。通过HPLC分离的4a-羟基黄素非对映体（+）-3和（-）-3通过电子圆二色性（CD）光谱表征。它们的绝对构型在4a的位置，第一次，确定通过比较实验CD光谱与那些计算通过依赖于时间的密度泛函理论（TDDFT）DFT优化后得到的结构进行了广泛的构象分析。
The biological action of flavoenzymes, such as flavin adenine dinucleotide (FAD)-containing monooxygenase, involves the formation of oxygenated flavin derivatives, such as 4a-hydroperoxyflavin and 4a-hydroxyflavin, in which a new center of chirality is created at the 4a position during the enzymatic reactions. So far, the absolute configuration of this center of chirality in natural 4a-oxygenated flavins has remained unknown in spite of its key importance for the diverse functions of flavoenzymes. Herein, we report the 4a-hydroxy adduct 3 of 3-benzyl-5-ethyl-10-(tetraacetyl-D-ribityl)flavinium (1), one of the key intermediates involved in the enantioselective organocatalytic oxidation of sulfides to sulfoxides. The 4a-hydroxyflavin diastereomers (+)-3 and (-)-3, separated by HPLC, were characterized by electronic circular dichroism (CD) spectroscopy. Their absolute configurations at the 4a position were, for the first time, determined by comparing experimental CD spectra with those calculated by means of time-dependent density functional theory (TDDFT) on DFT-optimized structures obtained after an extensive conformation analysis.