ATRIPISOMERIC FLAVOENZYME MODELS WITH A MODIFIED PYRIMIDINE RING : SYNTHESES, PHYSICAL PROPERTIES, AND STEREOCHEMISTRY IN THE REACTIONS WITH NAD(P)H A NALOGS
ATRIPISOMERIC FLAVOENZYME MODELS WITH A MODIFIED PYRIMIDINE RING : SYNTHESES, PHYSICAL PROPERTIES, AND STEREOCHEMISTRY IN THE REACTIONS WITH NAD(P)H A NALOGS
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具有修饰嘧啶环的去角异构黄酶模型：与 NAD(P)H A 类似物反应中的合成、物理性质和立体化学
DOI：
10.1021/jo961799t
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发表时间：
1996
影响因子：
3.6
通讯作者：
F. Yoneda
中科院分区：
文献类型：
--
作者：
A. Ohno;J. Kunitomo;Y. Kawai;T. Kawamoto;M. Tomishima;F. Yoneda
合成了嘧啶环上具有轴向手性的5-脱氮黄素衍生物（3-芳基-10-（4-叔丁基苯基）嘧啶并[4，5-B]喹啉-2，4（3 H，10 H）-二酮），并测定了部分衍生物的对映体动力学。这些化合物的绝对构型已确定的X-射线晶体学分析和化学反应的第一次阻转异构体flavoenzyme模型。1-苄基-1，4-二氢烟酰胺（BNAH）与3-[2-（羟甲基）苯基]衍生物1的对映异构体区分（净）取代基转移反应表明，Mg 2+的存在或不存在改变了反应面的选择性，1的羟甲基在Mg 2+不存在时产生空间位阻，而在Mg 2+存在时促进BNAH的接近.与手性1，4-二氢-2，3-二氢-1H-吡喃的不对称（净）脱氢转移反应，4-二甲基-N-（α-甲基苯甲基）-1-丙基烟酰胺（Me 2 PNPH）预测这两个分子在过渡态的最有利的分子间排列是其中1的嘧啶环和Me 2 PNPH的氨基甲酰基倾向于彼此面对并且它们的分子平面的最大重叠被实现而不管存在或不含Mg 2+。这种排列模拟了黄素酶活性位点中FAD和NADPH的排列。目前的结果表明，一个积极有利的重叠的分子平面的黄素和NAD（P）H辅酶，以及一个显着的影响，从脱辅基酶的功能基团接近黄素辅酶的立体化学的生物氧化还原反应。
Optically active 5-deazaflavin derivatives (3-aryl-10-(4-tert-butylphenyl)pyrimido[4,5-b]quinoline-2,4(3H,10H)-dione) with an axial chirality at the pyrimidine ring have been synthesized, and the kinetics of enantiomerization have been measured for some of them. The absolute configurations of these compounds have been determined by X-ray crystallographic analysis and chemical reactions for the first time in atropisomeric flavoenzyme models. Enantioface-differentiating (net) hydride-transfer reactions with 1-benzyl-1,4-dihydronicotinamide (BNAH) have revealed that the selectivity of the reacting face of the 3-[2-(hydroxymethyl)phenyl] derivative1changes depending on the presence or absence of Mg2+; the hydroxymethyl group of1exerts steric inhibition in the absence of Mg2+, whereas it facilitates the approach of BNAH in the presence of Mg2+. Asymmetric (net) hydride-transfer reactions with chiral 1,4-dihydro-2,4-dimethyl-N-(α-methylbenzyl)-1-propylnicotinamide (Me2PNPH) predict that the most favorable intermolecular arrangement of these two molecules at the transition state is the one in which the pyrimidine ring of1and the carbamoyl group of Me2PNPH tend to face each other and the maximum overlap of their molecular planes is achieved regardless of the presence or absence of Mg2+. The arrangement mimics that of FAD and NADPH in the active site of a flavoenzyme. The present result indicates an energetically favorable overlap of the molecular planes of a flavin and an NAD(P)H coenzyme, as well as a significant influence of functional groups from an apoenzyme in proximity to a flavin coenzyme on the stereochemistry of biological redox reactions.