6870-79-7Relevant articles and documents
Synthesis, characterization, and solid state dynamic studies of a hydrogen bond-hindered steroidal molecular rotor with a flexible axis
Mayorquín-Torres, Martha C.,Colin-Molina, Abraham,Pérez-Estrada, Salvador,Galano, Annia,Rodríguez-Molina, Braulio,Iglesias-Arteaga, Martín A.
, p. 3768 - 3779 (2018)
A novel steroid molecular rotor was obtained in four steps from the naturally occurring spirostane sapogenin diosgenin. The structural and dynamic characterization was carried out by solution NMR, VT X-ray diffraction, solid state 13C CPMAS, and solid state 2H NMR experiments. They allowed the identification of a fast dynamic process with a frequency of 14 MHz at room temperature, featuring a barrier to rotation Ea = 7.87 kcal mol-1. The gathered experimental evidence indicated the presence of a hydrogen bond that becomes stronger as the temperature lowers. This interaction was characterized using theoretical calculations, based on topological analyses of the electronic density and energies. In addition, combining theoretical calculations with experimental measurements, it was possible to propose a partition to Ea (～8 kcal/mol) into three contributions, that are the cost of the intrinsic rotation (～2 kcal/mol), the hydrogen bond interaction (～2 kcal/mol), and the packing effects (～2-3 kcal/mol). The findings from the present work highlight the relevance of the individual components in the function of molecular machines in the solid state.
Microbial transformation of diosgenin to diosgenone by Wickerhamomyces anomalus JQ-1 obtained from Naxi traditional Jiu Qu
Li, Liangqun,Zhao, Yanqiang,Lang, Bayi,Xie, Yuying,Shaowu Meng, Manfred,He, Yun,Yang, Lixin,Liu, Aizhong
, (2020)
Diosgenone [(20S,22R,25R)-spirost-4-en-3-one, C27H40O3] has been considered as a potential therapeutic alternative remedy for malaria. An efficient and economical approach of microbial transformation with diosgenin to diosgenone by the yeast strain Wickerhamomyces anomalus JQ-1 from Naxi traditional Jiu Qu was developed in this study. Chromatographic analysis confirmed that 85% of 0.1 mM diosgenin was transformed to diosgenone within 72 h. This research demonstrates that diosgenin could be converted to diosgenone through two-step pathway including 3β-hydroxyl oxidation and double bond isomerization rather than through one-step pathway, which prompted a further inference that the oxidation activity in W. anomalus JQ-1 has the same function with the Oppenauer-type oxidation which can convert diosgenin into diosgenone. Gaining specific functional strains from traditional fermented products will be a potential direction and ethnobotanical researches could provide helps with discovery and utilization of microbial resources.
Synthesis of diosgenin derivatives by A and B ring modifications and low-valent titanium (Ti0)-catalysed McMurry coupling reactions and designing to create novel biological agents
Ilkar Erdagi, Sevinc,Yildiz, Ufuk
, (2022/02/07)
Diosgenin is a steroidal sapogenin ((25R)-spirost-5-en-3β-ol) occurs abundantly in therapeutic herbs such as Dioscorea alata, Smilax China, and Trigonella foenum graecum. It demonstrates a wide range of pharmacological activities and medicinal properties in a large of experimental and theoretical studies. It also constitutes an important class of compounds for new drug development. In the current study, diosgenin derivatives were synthesized and designed, aiming to discover new steroid-based biological agents. In this work, new diosgenin derivatives were synthesized through low-valent titanium (Ti0)-catalyzed McMurry coupling reaction and structural modifications to the A- and B- rings in the diosgenin. McMurry reaction gave the A-nor and B-nor derivatives in by the intramolecular reductive dimerization of carbonyl compounds in the presence of low-valent titanium agents, in moderate yields (46–47%). The modification reactions on the A and B rings of diosgenin were accomplished by using efficient reagents to give three different series, in moderate to high yields (55–97%). The structures of all novel derivatives were confirmed by FTIR, 1H NMR, 13C NMR, and HRMS methods.
Azasteroids from diosgenin: Synthesis and evaluation of their antiproliferative activity
Martínez-Gallegos, Anselmo A.,Guerrero-Luna, Gabriel,Ortiz-González, Alejandra,Cárdenas-García, Maura,Bernès, Sylvain,Hernández-Linares, María Guadalupe
, (2020/12/23)
In this work, we report the synthesis of two new azasteroids through the modification of the A and B rings of diosgenin 1. The 4-azasteroid derivative 12 was prepared in three steps using the α,β-insaturated-3-keto compound 11 as a precursor, which was first oxidized with KMnO4/KIO4 followed by an oxidative cleavage of ring A, and subsequently cyclized with an ammonium salt, under focused microwave irradiation for a short time of 3 min. A second azasteroid was synthesized, for which the key step was the Beckmann rearrangement of ring B of the oxime 16, affording the lactam-type enamide 17 in good yield. The methodologies developed for the synthesis of the precursors derivatives 10 and 11 contribute to improved yields, compared to those reported in the literature. The biological activity of the azasteroidal compounds 12 and 17 and their precursors has been evaluated in cervical cancer cells (HeLa), colon (HCT-15), and triple negative breast cancer (MDA-MB-231) lines.
Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease
Zhou, Li-Cheng,Liang, Ying-Fan,Huang, Yi,Yang, Gui-Xiang,Zheng, Lu-Lu,Sun, Jia-Min,Li, Yang,Zhu, Fu-Li,Qian, He-Wen,Wang, Rui,Ma, Lei
, (2021/04/19)
The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aβ (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aβ1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aβ1-42 was ?40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aβ1-42. The predicted values of brain/blood partition coefficient (?0.733) and polar surface area (85.118 ?2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aβ-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.
Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia
Yang, Gui-Xiang,Sun, Jia-Min,Zheng, Lu-Lu,Zhang, Li,Li, Jie,Gan, Hai-Xian,Huang, Yan,Huang, Jin,Diao, Xing-Xing,Tang, Yun,Wang, Rui,Ma, Lei
, (2021/04/02)
A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
Steroid sapogenin derivative as well as preparation method and application thereof
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Paragraph 0130-0134, (2020/11/09)
The invention discloses a steroid sapogenin derivative represented by general formula (1), and a pharmaceutically acceptable salt and a pharmaceutical composition thereof. The steroid sapogenin derivative disclosed by the invention has a protective effect
Ruthenium-Catalyzed Dehydrogenation of Alcohols with Carbodiimide via a Hydrogen Transfer Mechanism
Sueki, Shunsuke,Matsuyama, Mizuki,Watanabe, Azumi,Kanemaki, Arata,Katakawa, Kazuaki,Anada, Masahiro
, p. 4878 - 4885 (2020/06/02)
Ruthenium-catalyzed oxidative dehydrogenation of alcohols using carbodiimide as an efficient hydrogen acceptor has been developed. The protocol exhibits wide substrate scope with good to excellent yields. The results of the kinetic analysis indicated that the reaction mechanism includes the hydrogen transfer process and that the addition of carbodiimide is essential for the reaction system, and the resulting amidine also could react as a hydrogen acceptor.
Synthesis of Symmetrical and Hybrid Dimeric Steroids by Double Suzuki-Miyaura Cross Coupling of 4-Bromo-3-oxo Steroids and Benzene-1,4-diboronic Acid
Flores-álamo, Marcos,Iglesias-Arteaga, Martín. A.,Mayorquín-Torres, Martha C.,Santiago-Sampedro, Gerardo I.
, p. 2909 - 2914 (2019/07/22)
Two symmetrical dimers and one hybrid dimer in which the steroid cores are connected by a 1,4-phenylene moiety were obtained by double Suzuki-Miyaura cross coupling of benzene-1,4-diboronic acid with 4-bromo-4-en-3-oxosteroids derived from cholesterol and diosgenin. Detailed NMR characterization of the obtained dimers is described.
Diosgenin derivatives, and pharmaceutical compositions thereof and application thereof
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Paragraph 0108-0111, (2019/01/24)
The invention relates to diosgenin derivatives. The structural formula of the diosgenin derivatives is as shown in a general formula (1) which is described in the specification. The invention also provides pharmaceutical compositions of the diosgenin derivatives and application thereof. According to the invention, systematic structural modification directed at double bonds at position 3 and position 5/6 of a lead compound is performed for the first time so as to synthesize a series of novel compounds; and the results of activity tests of the novel compounds at related targets show that most ofthe novel compounds have better activity than the activity of the lead compound and are very valuable for the treatment of neurodegenerative diseases. Thus, the diosgenin derivatives overcome defectsof conventional diosgenin derivatives and have important significance.
