ParaHydrogen Polarized Ethyl-[1-(13) C]pyruvate in Water, a Key Substrate for Fostering the PHIP-SAH Approach to Metabolic Imaging.
ParaHydrogen Polarized Ethyl-[1-(13) C]pyruvate in Water, a Key Substrate for Fostering the PHIP-SAH Approach to Metabolic Imaging.
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DOI：
10.1002/cphc.202100062
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发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Reineri F
中科院分区：
文献类型：
--
作者：
Carrera C;Cavallari E;Digilio G;Bondar O;Aime S;Reineri F
报道了乙烯基-[1 - 13 C]丙酮酸酯的有效合成，其中通过仲氢诱导极化（PHIP）获得13 C超极化（HP）乙基-[1 - 13 C]丙酮酸酯。由于丙酮酸的固有不稳定性，即使在温和的反应条件下也会导致反应混合物快速降解，因此乙烯基酯已通过更稳定的缩酮衍生物的中间体合成。使用ParaHydrogen氢化的乙基-[1 - 13 C]丙酮酸酯的13 C和1H超极化与在更广泛使用的烯丙基衍生物上观察到的超极化进行了比较。已经证明，从仲氢质子到13 C的自旋顺序转移在乙基上比在烯丙基酯上更有效，这是由于涉及更大的J耦合。该HP产品的生物学应用所需的主要要求已得到满足，即：获得了具有良好的13 C极化水平（4.8%）的高浓度（40 mM）产物的水溶液。 已观察到酯酶催化的HP乙基-[1 - 13 C]丙酮酸酯的体外代谢转化。该底物似乎是使用PHIP超极化探针进行体内代谢研究的良好候选物。 通过PHIP-SAH实现13 C超极化-[1 - 13 C]丙酮酸乙酯：已通过新的合成路线在实验室规模上制备乙烯基-[1 - 13 C]丙酮酸酯。在其用p-H2氢化和磁化转移（通过MFC）之后，在高浓度（40 mM）和良好极化水平（4.8%）的水溶液中获得了极化的[1 - 13 C]丙酮酸乙酯。 最后，观察到HP乙基-[1 - 13 C]丙酮酸在酯酶催化下体外转化为[1 - 13 C]丙酮酸。
An efficient synthesis of vinyl‐[1‐13C]pyruvate has been reported, from which 13C hyperpolarized (HP) ethyl‐[1‐13C]pyruvate has been obtained by means of ParaHydrogen Induced Polarization (PHIP). Due to the intrinsic lability of pyruvate, which leads quickly to degradation of the reaction mixture even under mild reaction conditions, the vinyl‐ester has been synthesized through the intermediacy of a more stable ketal derivative. 13C and 1H hyperpolarizations of ethyl‐[1‐13C]pyruvate, hydrogenated using ParaHydrogen, have been compared to those observed on the more widely used allyl‐derivative. It has been demonstrated that the spin order transfer from ParaHydrogen protons to 13C, is more efficient on the ethyl than on the allyl‐esterdue to the larger J‐couplings involved. The main requirements needed for the biological application of this HP product have been met, i. e. an aqueous solution of the product at high concentration (40 mM) with a good 13C polarization level (4.8 %) has been obtained. The in vitro metabolic transformation of the HP ethyl‐[1‐13C]pyruvate, catalyzed by an esterase, has been observed. This substrate appears to be a good candidate for in vivo metabolic investigations using PHIP hyperpolarized probes. 13C hyperpolarized ethyl‐[1‐13C]pyruvate by means of PHIP‐SAH: Vinyl‐[1‐13C]pyruvate has been prepared on laboratory scale through a new synthesis route. After its hydrogenation with p‐H2 and magnetization transfer (via MFC), polarized ethyl‐[1‐13C]pyruvate has been obtained in aqueous solution at high concentration (40 mM) and good polarization level (4.8 %). In the end, the in‐vitro conversion of HP ethyl‐[1‐13C]pyruvate into [1‐13C]pyruvate catalysed by an esterase, has been observed.
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影响因子：
2.2
作者：
Baer, Sebastien;Lange, Thomas;Hoevener, Jan-Bernd
通讯作者：
Hoevener, Jan-Bernd
通过侧臂氢化的1-（13）c-乙酸盐和1-（13）c-丙酮酸的非饱和前体的合成。
影响因子：
4.1
作者：
Chukanov NV;Salnikov OG;Shchepin RV;Kovtunov KV;Koptyug IV;Chekmenev EY
通讯作者：
Chekmenev EY
DOI：
10.1073/pnas.0601319103
发表时间：
2006-07-25
影响因子：
11.1
作者：
Golman, Klaes;in't Zandt, Rene;Thaning, Mikkel
通讯作者：
Thaning, Mikkel
影响因子：
4.8
作者：
Kurhanewicz, John;Vigneron, Daniel B.;Malloy, Craig R.
通讯作者：
Malloy, Craig R.
影响因子：
11.2
作者：
Golman, Klaes;in't Zandt, Rene;Ardenkjaer-Larsen, Jan Henrik
通讯作者：
Ardenkjaer-Larsen, Jan Henrik