- 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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- PROCESS FOR THE PREPARATION OF A CHIRAL PROSTAGLANDIN ENOL INTERMEDIATE AND INTERMEDIATE COMPOUNDS USEFUL IN THE PROCESS
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The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing t
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Page/Page column 30-31
(2021/06/26)
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- Preparation method for prostaglandins drug intermediate
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The invention discloses a preparation method for (3aR,4R,5R,6aR)-4-aldehyde-hexahydro-2-oxo-2H-cyclopentano[b]furan-5-yl[1,1'-biphenyl]-4-foremate, and belongs to the technical field of the medical intermediate preparation. Compared with a former Pfitzner
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Paragraph 0059-0091
(2019/10/04)
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- He fluorine front row element intermediate preparation method (by machine translation)
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The invention discloses he fluorine front row element intermediate, i.e. formula 5 compound preparation method, including the use of biphenyl formyl protected Corey lactone as raw materials, through oxidation, HWE connected side chain, fluorinated, hydrolysis of deprotection step. Preparation method of this invention has the operability is strong, stable process, intermediates for the preparation of white powder, good stability. (by machine translation)
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Paragraph 0043; 0044; 0045; 0046; 0047; 0048
(2018/05/16)
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- An improved and efficient process for the preparation of (+)-cloprostenol
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Abstract An improved and efficient synthesis of (+)-cloprostenol has been accomplished in nine steps and 26% overall yield from commercially available (-)-Corey lactone 4-phenylbenzoate alcohol 1. The present route avoids tedious purifications and require
- Chen, Yi,Yan, Hui,Chen, Hui-Xuan,Weng, Jiang,Lu, Gui
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p. 392 - 396
(2015/06/02)
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- PROCESS FOR THE PREPARATION OF TRAVOPROST
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The invention relates to a process for the preparation of travoprost of formula(I), comprising that, the compound of formula (II), is stereoselectively reduced, the resulting compound of formula (III), is if desired crystallized, the lactone group of the
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Page/Page column 9-12
(2013/07/05)
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- AN IMPROVED AND SCALABLE PROCESS FOR PREPARATION OF PROSTAGLANDIN DERIVATIVES AND INTERMEDIATES THEREOF
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Provided herein is an improved, commercially viable and industrially advantageous process for the preparation of a prostaglandin derivatives and intermediates thereof, in high yield and purity.
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Page/Page column 27
(2013/11/19)
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- PROCESS FOR THE PREPARATION OF F-SERIES PROSTAGLANDINS
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A process for the synthesis and purification of F-series prostaglandin compounds and synthetic intermediates used to prepare them. The synthetic intermediates are solid and may be purified by precipitation and therefore may form the representative F-series prostaglandin compounds such as latanoprost, bimatoprost, fluprostenol, cloprostenol, and substituted analogs therefrom in highly pure forms.
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Page/Page column 61-62
(2011/05/05)
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- IMPROVED PROCESS FOR THE PREPARATION OF PROSTAGLANDINS AND ANALOGUES THEREOF
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The present invention relates to an improved process for the preparation of prostaglandin and prostaglandin analogues, particularly PGF2α derivatives.
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Page/Page column 13
(2010/11/03)
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- Bimatoprost crystalline form I
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The invention provides a novel polymorphic form I of crystalline bimatoprost, method for preparation thereof and new crystalline intermediates in the preparation. This form I of crystalline bimatoprost is used in purification of crude bimatoprost and in storage of bimatoprost as active pharmaceutical intermediate. Use of the physical form of bimatoprost in the manufacture of a medicament is also disclosed.
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Page/Page column 10
(2009/07/10)
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- Composition and method for the treatment of psoriasis
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The use of a prostaglandin A2 derivative, and prodrugs of the compound, for the manufacture of a medicament for the treatment and/or alleviation of psoriasis is presented, as well as a method of treatment, involving the topical application of such prostaglandins. Compositions containing a therapeutically active, and physiologically acceptable amount of the above compound or derivatives thereof, as such or in the form of a prodrug, in a suitable vehicle are also described. Importantly, the derivatives can be applied in therapeutically active amounts without or with only minimal side effects, such as hyperemia, irritation or pain.
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Page/Page column 4
(2008/06/13)
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- Phenyl-Substituted Prostaglandins: Potent and Selective Antiglaucoma Agents
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A series of phenyl-substituted analoques of prostaglandin F2α (PGF2α) were prepared and evaluated for ocular hypotensive effect and side effects in different animal models.In addition, the activity of the analogues on FP receptors was studied in vitro.The results were compared with those of PGF2α and its isopropyl ester.The phenyl-substituted PGF2α analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF2α or its isopropyl ester.The analogues exhibited high activity on FP receptors in a stereoselective manner for the 15a-hydroxyl group.
- Resul, Bahram,Stjernschantz, Johan,No, Kiyo,Liljebris, Charlotta,Selen, Goeran,et al.
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p. 243 - 248
(2007/10/02)
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- Prostaglandin F2α photoaffinity probes: 18-phenoxy-19,20-bisnorprostanoids bearing perfluorinated aryl azides
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The synthesis of a potential prostaglandin F2α photoaffinity probe involved the preparation of an 18-phenoxy-19,20-bisnorprostanoid in which the phenoxy group possessed an iodine substituent and a perfluorinated aryl azide.
- Golinski, Miroslaw,Heine, Michal,Watt, David S.
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p. 1553 - 1556
(2007/10/02)
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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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- Prostaglandin Photoaffinity Probes: Synthesis and Biological Activity of Azide-Substituted 16-Phenoxy- and 17-Phenyl-PGF2α Prostaglandins
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The development of a prostaglandin PGF2α photoaffinity probe led to the synthesis and biological evaluation of azide-substituted 17-phenyl-18,19,20-trinorprostaglandin F2α and 16-phenoxy-17,18,19,20-tetranorprostaglandin F2α derivatives.Two approaches for the preparation of iodinated versions of these prostaglandins were evaluated: (1) iodination of a phenyl azide bearing an activating hydroxyl group and (2) iodination of an aniline precursor to the phenyl azide group and subsequent conversion of the aniline to the phenyl azide.In the first approach, 17-(4-azido-2-hydroxyphenyl)-18,19,20-trinorprostaglandin F2α, 16-(5-azido-3-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F2α, and 16-(4-azido-2-hydroxyphenoxy)-17,18,19,20-tetranorprostaglandin F2α were prepared by using the Corey synthesis, but were biologically inactive presumably as a result of the hydrophilic phenolic hydroxyl group.In the second approach, the iodination of a 17-(4-aminophenyl)-18,19,20-trinorprostaglandin F2α derivative delivered 17-(4-azido-3-iodophenyl)-18,19,20-trinorprostaglandin F2α, which exhibited competitive binding with natural PGF2α to ovine luteal cells and to plasma membranes of bovine corpora lutea. -17-(4-Azido-3-iodophenyl)-18,19,20-trinorprostaglandin F2α was utilized in a preliminary photoaffinity cross-linking experiment.
- Kawada, Kenji,Dolence, E. Kurt,Morita, Hiroyuki,Kometani, Tadashi,Watt, David S.,et al.
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p. 256 - 264
(2007/10/02)
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- SYNTHESIS OF THE MAJOR URINARY METABOLITE OF PROSTAGLANDIN D2
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Starting from the Corey lactone (3), the total synhesis of a specific urinary metabolite of prostaglandin D2, viz., (Z)-9α,11β-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (1) and its 5E-isomer is described.The synthetic mater
- Prakash, Chandra,Saleh, Samir,Roberts, L. Jackson,Blair, Ian A.,Taber, Douglass F.
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p. 2821 - 2826
(2007/10/02)
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