- 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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- Antifungal activity of 1′-homo-N-1,2,3-triazol-bicyclic carbonucleosides: A novel type of compound afforded by azide-enolate (3+2) cycloaddition
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The first report of 1′-homo-N-1,2,3-triazol-bicyclic carbonucleosides (7a and 7b) is described herein. Azide-enolate (3+2) cycloaddition afforded the synthesis of this novel type of compound. Antifungal activity was evaluated in vitro against four filamentous fungi (Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis) as well as nine species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 7a and 7b are promising candidates for complementary biological studies due to their good activity against Candida spp.
- González-Calderón, Davir,Mejía-Dionicio, María G.,Morales-Reza, Marco A.,Aguirre-de Paz, José G.,Ramírez-Villalva, Alejandra,Morales-Rodríguez, Macario,Fuentes-Benítes, Aydeé,González-Romero, Carlos
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- A short synthesis of optically active corey lactone by means of the dirhodium(II)-catalyzed intramolecular C-H insertion reaction of an α-diazo ketone
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Optically active Corey lactone 8 has been synthesized using a dirhodium(II)-catalyzed intramolecular C-H insertion reaction of chiral α- diazo-β-oxo ester 2 as a key step.
- Yakura, Takayuki,Yamada, Seiji,Azuma, Miki,Ueki, Akiharu,Ikeda, Masazumi
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p. 973 - 974
(2007/10/03)
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- RESOLUTION OF A RACEMIC COREY LACTONE via ENANTIOSELECTIVE ESTERIFICATION
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The (-)-enantiomer of Corey lactone Ia has been separated from its (+)-enantiomer Ib via enantioselective esterification of the latter using glycerol tributyrate and a catalytic amount of lipase from Candida cylindracea (EC 3.1.1.3) in an aprotic solvent
- Vesely, Ivan,Palecek, Jaroslav,Stibor, Ivan
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p. 357 - 361
(2007/10/02)
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- PREPARATION OF OPTICALLY PURE ENANTIOMERS OF COREY LACTONE BY RESOLUTION OF THE RACEMATE
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Racemic hydrogen butanedioates (IIa, IIb) and hydrogen pentanedioates (IIIa, IIIb), prepared by reaction of racemic Corey alcohol Ia, Ib with the corresponding acid anhydride, were resolved by optically active bases to give the optically pure diastereoisomeric salts from which the individual enantiomers of hydrogen butanedioate IIa and IIb and hydrogen pentanedioate IIIa and IIIb were liberated.Acid-catalyzed transesterification with methanol converted these optically pure enantiomers into the pure (-)-enantiomer Ia and (+)-enantiomer Ib of the Corey lactone.
- Zak, Bohumil,Vesely, Ivan,Neumitka, Karel,Palecek, Jaroslav
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p. 1690 - 1700
(2007/10/02)
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