- A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost guided by biocatalytic retrosynthesis
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Development of efficient and stereoselective synthesis of prostaglandins (PGs) is of utmost importance, owing to their valuable medicinal applications and unique chemical structures. We report here a unified synthesis of PGs cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost from the readily available dichloro-containing bicyclic ketone6aguided by biocatalytic retrosynthesis, in 11-12 steps with 3.8-8.4% overall yields. An unprecedented Baeyer-Villiger monooxygenase (BVMO)-catalyzed stereoselective oxidation of6a(99% ee), and a ketoreductase (KRED)-catalyzed diastereoselective reduction of enones12(87?:?13 to 99?:?1 dr) were utilized in combination for the first time to set the critical stereochemical configurations under mild conditions. Another key transformation was the copper(ii)-catalyzed regioselectivep-phenylbenzoylation of the secondary alcohol of diol10(9.3?:?1 rr). This study not only provides an alternative route to the highly stereoselective synthesis of PGs, but also showcases the usefulness and great potential of biocatalysis in construction of complex molecules.
- Chen, Fener,Huang, Zedu,Jiang, Meifen,Li, Weijian,Tang, Pei,Ye, Baijun,Zhang, Guo-Tai,Zhu, Kejie
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p. 10362 - 10370
(2021/08/16)
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- Treatment of inflammation with 15-keto-prostaglandin compounds
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A method of treatment of inflammatory diseases which comprises administering, to a subject in need of such treatment, an anti-inflammatorily effective amount of a 15-keto-prostaglandin compound.
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- Promotion of wound-healing with 15-keto-prostaglandin compounds
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A method for promoting healing of wound which comprises administering, to a subject in need of such treatment, a wound-healingly effective amount of a 15-ketoprostaglandin compound.
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- Treatment of pancreatic disease with 15-keto-prostaglandin compounds
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A method of treatment of pancreatic disease which comprises administering, to a subject in need of such treatment, a 15-keto-prostaglandin compound in an amount effective in treatment of pancreatic disease.
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- 15-keto-prostaglandin compound for improvement of encephalic function
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A method of treatment for improving encephalic function which comprises administering, to a subject in need of such treatment, a 15-keto-prostaglandin compound in an amount effective for improvement of encephalic function.
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- Intramolecular Cycloadditions of Keteniminium Salts. A Practical Asymmetric Synthesis of Prostaglandins
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The intramolecular cycloaddition of keteniminium salt 5 derived from (2S,5S)-dimethylpyrrolidine is the key step of a short synthetic route toward prostaglandins.
- Chen, Lian-yong,Ghosez, Leon
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p. 1181 - 1184
(2007/10/02)
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