Synthesis of heme substituted with fluoro and perfluoroalkyl groups, and application of fluorine nuclear to NMR-probe

定点氟基(-F，-CF3)引入酶反应、辅酶和蛋白质是阐明生物体系中功能-结构关系的一种独特方法。以掺入肌红蛋白为目标，合成了几种氟化高铁血红素，并通过电化学测试和核磁共振表征了其独特的物理化学性质。用改进的方法合成了起始吡咯β-二氟吡咯。首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容1951、73、1103-1104)。然后，β-二氟吡咯和β-单氟吡咯发生偶联反应，合成了一种新的含氟二氢吡咯烷。氟化氢溴化二吡咯亚胺和另一种氢溴化二吡咯亚胺的环化反应得到了低产率(2，3，7-TFP：1.2%)的位置特异性的氟卟啉。通过氧化环化反应以中等产率(14%)得到了对称的双三氟甲基化卟啉(2，8-DPF)。重组肌红蛋白与2，8-DPF形成的甲基型、脱氧型和氧型加合物的吸收光谱与天然肌红蛋白相似。重组肌红蛋白与2，8-DPF、Mesohemin和天然高铁血红素的光谱相似性表明，这些肌红蛋白的结构基本相同，因此，环氟化的高铁血红素可能在各种血红素酶的重组研究中作为一种仿制的血红素有用。

Site-specific fluoro-groups(-F, -CF_3) introduction to a enzymatic reaction, coenzyme and protein has been a unique method to elucidate function-structure relationship in biological systems. Aiming at incorporation into Myoglobin, several fluorinated hemes have been synthesized and their particular physicochemical properties have been characterized by electrochemical measurement and ^<19>F NMR.The starting pyrrole β-difluoropyrrole was prepared by the improved method (ref. Henne, A.L. ; Zimmer, W.F. J.Am.Chem.Soc. 1951, 73, 1103-1104). Then, coupling reactions of β-difluoropyrrole and β-monofluoropyrrole gave rise to a new fluorinated dipyrromethene hydrobromide. Cyclization of fluorinated dipyrromethene hydrobromide and another dipyrromethene hydrobromide gave the site specific fluoroporphyrin in low yield (2,3,7-TFP:1.2%).Symmetrical bis-trifluoromethylated porphyrin (2,8-DPF) was obtained by oxidative cyclization in moderate yield (14 %).The ^<19>F NMR spectrum of 2,8-DPF was observed a single signal at δ-103.77ppm downfield from trifluoroacetic acid (TFA) as an external reference.2,8-DPF was incorporated into sperm whale apo-myoglobin. The pattern of absorption spectra of the met-, deoxy- and oxy-adduct-forms of reconstituted myoglobin with 2,8-DPF was similar to the native myoglobin. The pattern of spectral similarities among the reconstituted myoglobin with 2,8-DPF, mesohemin and native hemin indicate that the structure of these myoglobins are much the same.Thus, the ring-fluorinated heme may be useful as a mimicking prosthetic heme in the reconstitutional studies of various heme enzymes.