锰卟啉酶课件.pptVIP

Oxidative Aliphatic C-H Fluorination with Fluoride Ion Catalyzed by a Manganese Porphyrin 人体内代谢药物的主要酶是细胞色素P450超家族(Cytochrome P450 proteins, CYP)，它们是一类主要存在于肝脏、肠道中的单加氧酶，多位于细胞内质网上，催化多种内、外源物质的（包括大多数临床药物）代谢。 P450酶能通过其结构中的血红素中的铁离子传递电子，氧化异源物，增强异源物质的水溶性，使它们更易排出体外。 与细胞色素P450相比，简单的金属卟啉络合物是使氧原子从亚碘酰基芳香烃、叔胺氧化物、次氯酸、高碘酸和过氧化氢转移到有机物上的很有潜力的氧化剂。金属卟啉络合物中的卟啉大环、中心金属原子和轴向阴离子配体是影响络合物催化活性的关键因素。 反应体系 50℃，6~8h N2,3:1比例的CH3CN/CH2Cl溶剂中 1.5mmol 底物 4.5mmol AgF 6~8 mol % 的催化剂 0.3 equivalent TBAF.3H2O 6~8 equivalent 亚碘酰苯 Kinetic isotope effect--动力学同位素效应 在化学反应过程中，反应物因同位素取代而改变了能态，从而引起化学反应速率的差异。 Deuterium kinetic isotope effects (KIEs) were evaluated by the reaction of a 1:1 mixture of cyclohexane and cyclohexane-d12, producing an intermolecular competitive KIE of 6.1. A similar value (5.7) was observed with a mixture of ethylbenzene and ethylbenzene-d10. The large KIE indicates that C-H bond cleavage is the rate-limiting step in the reaction, consistent with typical manganese porphyrin–catalyzed hydroxylation reactions. Furthermore, reaction of norcarane, a diagnostic radical clock substrate (2), afforded 2-fluoronorcaranes and a significant amount of the rearranged fluorinated product, 3- fluoromethylcyclohexene (7), which is indicative of a C radical ring-opening process (Table 1, entry 6). * LOGO SCIENCE 14 SEPTEMBER 2012 SCI 31.364 普林斯顿大学Groves实验室在Science上报道,他们制造出一种人造酶，可以充当催化剂用氟原子替代某些药物分子中的氢，这种交换可以使得分子稳定，使得其能够耐受可导致药物失活或生成有毒副作用的肝酶。 这项工作是从Groves实验室对细胞色素P450的研究工作中发展而来的。 亚碘酰苯 四丁基氟化铵 Cycloalkanes afforded monofluorinated products in ~50% yield. Typically, conversions were ~70%, with small amounts (15 to 20%) of alcohols and ketones also being produced. No products were detected in control experiments that omitted the manganese porphyrin or iodosylbenzene, whereas a ~2:1 ratio of oxygenated to fluorinated products was formed in the absence of tetrabutylammonium fluoride. Only oxygenated products were f