使用DFT NMR计算和DP4+概率确定孕激素的氧化衍生物的立体化学确定
Cassia R Rambo1, Samuel F C Paula2, André L M Porto2
1Departamento de Engenharias E Exatas, Universidade Federal Do Paraná, Setor Palotina, Rua Pioneiro, Palotina, PR, 2153, 85950-000, Brazil.
Journal of molecular modeling
|October 27, 2025
概括
这项研究使用核磁共振 (NMR) 计算来准确确定氧化孕激素衍生物的立体化学. 这些发现证实了酶化结果,并突出了该方法.
科学领域:
- 生物化学 生物化学
- 计算化学的计算化学
- 有机化学 有机化学
背景情况:
- 基化孕激素衍生物具有生物学意义,但通过NMR进行立体化学分析具有挑战性.
- 青 (Penicillium oxalicum CBMAI 1996) 产生单氧化 (prog-15-OH) 和二氧化 (prog-7,15-di-OH) 的孕激素.
研究的目的:
- 为了明确确定氧化孕激素衍生物的立体化学配置.
- 为了验证计算NMR在解决复杂的类固醇立体化学中的使用.
主要方法:
- 利用密度函数理论 (DFT) 进行几何优化和NMR屏蔽张量计算.
- 使用DP4+概率分析来比较实验和计算的NMR化学转移.
- 集成的量子NMR计算与统计验证用于立体化学赋值.
主要成果:
- 成功识别了15β-OH和7β,15β-di-OH异构体,其DP4+概率很高 (100%和99.8%).
- 证实了由Penicillium oxalicum进行酶性氧化过程的立体化学结果.
- 证明了对复杂类固醇结构的计算NMR的可靠性.
结论:
- 计算型NMR与统计分析相结合,提供了一种可靠的方法,用于对基化类固醇进行立体化学阐明.
- 这种方法解决了由微妙的NMR化学转移差异产生的模两可.
- 这项研究证实了由Penicillium oxalicum进行的孕激素生物转换的立体选择性.
相关概念视频
00:48¹H NMR of Labile Protons: Deuterium (²H) Substitution
1.3K
This lesson illustrates the role of deuterium substitution in simplifying the NMR spectrum of compounds comprising labile protons. One method employed is the use of deuterium. Amongst the three isotopes of hydrogen, deuterium (2H) has a nucleus composed of one proton and one neutron. When the D2O solvent is added to a pure dry ethanol solution, its labile proton is substituted with deuterium.
1.3K
01:20¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)
1.6K
When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
1.6K
01:13¹H NMR: Complex Splitting
1.8K
A proton M that is coupled to a proton X results in doublet signals for M. However, NMR-active nuclei can be simultaneously coupled to more than one nonequivalent nucleus. When M is coupled to a second proton A, such as in styrene oxide, each peak in the doublet is split into another doublet.
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
1.8K
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
1.7K
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
1.7K
01:07Proton (¹H) NMR: Chemical Shift
3.2K
Organic molecules primarily contain carbon and hydrogen atoms. While all the hydrogen isotopes are NMR-active, protium or hydrogen-1 is the most abundant. It has a significant energy separation between its nuclear spin states due to its large gyromagnetic ratio. As per Boltzmann's distribution, an increase in the energy separation implies a greater excess population of nuclei available for excitation, resulting in a strong NMR absorption signal.
Absorption signals of all the protium nuclei...
Absorption signals of all the protium nuclei...
3.2K
02:36Regioselectivity and Stereochemistry of Hydroboration
9.3K
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
9.3K