- A biocatalytic hydroxylation-enabled unified approach to C19-hydroxylated steroids
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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.
- Wang, Junlin,Zhang, Yanan,Liu, Huanhuan,Shang, Yong,Zhou, Linjun,Wei, Penglin,Yin, Wen-Bing,Deng, Zixin,Qu, Xudong,Zhou, Qianghui
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- 19 Hydroxylated cortisone derivative and preparation method 19 - hydroxyl androstenedione (by machine translation)
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The invention discloses 19 hydroxylated cortisone derivatives and a preparation method, namely 19 - hydroxyandrostenedione. Belong to organic synthesis and pharmacy field. To the invention, 19 - hydroxyl group can be used as a raw material, 19 - hydroxyl can be supported in a plurality of groups under the action of hydrogen peroxide, trimethyl iodosilane, palladium carbon, dichloro dicyanobenzene quinone, iodobenzene, sodium borohydride, sodium periodate and the like respectively. 19 - hydroxyl can be supported to 19 - respectively. B ring can be supported by structural modification 17. 21 And/or 19-position hydroxyl groups are substituted; cleavage 19 - hydroxyl groups may support many loose side chains. The preparation method of the essential intermediate 19 - hydroxyandrostenedione synthesized by the norethindrone contraceptive is greatly improved, and the drug production cost. (by machine translation)
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Paragraph 0049-0051
(2019/09/05)
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- New Syntheses of 19,21-Dihydropregn-4-ene-3,20-dione, 21-Hydroxy-19-norpregn-4-ene-3,20-dione, and 11β,19,21-trihydroxypregn-4-ene-3,20-dione
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19,21-Dihydroxypregn-4-ene-3,20-dione has been synthesized from 3β-acetoxypregn-5-en-20-one via the "hypoiodite reaction" , and Henbest acetoxylation at C-21; oxidation of the intermediate 21-monoacetate to 19-oxo derivative and alkaline cleavage gave 21-hydroxy-19-norpregn-4-ene-3,20-dione.A similar synthesis of 11β,19,21-trihydroxypregn-4-ene-3,20-dione from 3β-acetoxypregn-5-ene-11,20-dione proceeded through intermediates with the 11β-hydroxy function protected as its acetate.Unusual features mainly of conformational origin were observed in the presence of the 11β-acetoxy substituent; some were helpful to the synthesis, while others led to undesirable side reactions.
- Kirk, David N.,Yeoh, Boon Leng
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p. 2945 - 2952
(2007/10/02)
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