510-64-5Relevant articles and documents
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Sollman,P.B.
, p. 3559 - 3562 (1963)
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Kinetic solvent isotope effect in steady-state turnover by CYP19A1 suggests involvement of Compound 1 for both hydroxylation and aromatization steps
Khatri, Yogan,Luthra, Abhinav,Duggal, Ruchia,Sligar, Stephen G.
, p. 3117 - 3122 (2014)
CYP19A1, or human aromatase catalyzes the conversion of androgens to estrogens in a three-step reaction through the formation of 19-hydroxy and 19-aldehyde intermediates. While the first two steps of hydroxylation are thought to proceed through a high-valent iron-oxo species, controversy exists surrounding the identity of the reaction intermediate that catalyzes the lyase and aromatization reaction. We investigated the kinetic isotope effect on the steady-state turnover of Nanodisc-incorporated human CYP19A1 to explore the mechanisms of this reaction. Our experiments reveal a significant (～2.5) kinetic solvent isotope effect for the C10-C19 lyase reaction, similar to that of the first two hydroxylation steps (2.7 and 1.2). These data implicate the involvement of Compound 1 as a reactive intermediate in the final aromatization step of CYP19A1.
A biocatalytic hydroxylation-enabled unified approach to C19-hydroxylated steroids
Wang, Junlin,Zhang, Yanan,Liu, Huanhuan,Shang, Yong,Zhou, Linjun,Wei, Penglin,Yin, Wen-Bing,Deng, Zixin,Qu, Xudong,Zhou, Qianghui
, (2019/08/02)
Steroidal C19-hydroxylation is pivotal to the synthesis of naturally occurring bioactive C19-OH steroids and 19-norsteroidal pharmaceuticals. However, realizing this transformation is proved to be challenging through either chemical or biological synthesis. Herein, we report a highly efficient method to synthesize 19-OH-cortexolone in 80% efficiency at the multi-gram scale. The obtained C19-OH-cortexolone can be readily transformed to various synthetically useful intermediates including the industrially valuable 19-OH-androstenedione, which can serve as a basis for synthesis of C19-functionalized steroids as well as 19-nor steroidal drugs. Using this biocatalytic C19-hydroxylation method, the unified synthesis of six C19-hydroxylated pregnanes is achieved in just 4 to 9 steps. In addition, the structure of sclerosteroid B is revised on the basis of our synthesis.
Preparation method of 19-demethylation-4-androstenedione
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Paragraph 0007; 0010, (2017/08/30)
The invention discloses a preparation method of 19-demethylation-4-androstenedione and belongs to the technical field of medical intermediate processing. The preparation method comprises the following steps: (1) carrying out esterification reaction; (2) carrying out ketalation; (3) carrying out reduction reaction; (4) carrying out hydrolysis reaction; (5) carrying out esterification reaction; (6) carrying out addition reaction; (7) carrying out cyclization and hydrolysis reaction; (8) carrying out oxidation, dechloridation and ring-opening reaction; and (9) carrying out oxidation and decarboxylation reaction. The preparation method disclosed by the invention has the advantages that environmental pollution is small, usage amounts of a solvent and water are smaller, temperature sensitivity is low, control is easy, and yield is high; a chlorinating agent is adopted, so that reaction yield is increased; 1,3-dichloro-5,5-dimethylhydantoin is adopted, so that the reaction yield is further increased; and sodium hydrogen carbonate is adopted, so that final decarboxylic reaction yield is increased, and external standards and appearance of a product can be improved.
