- 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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- Concise, scalable and enantioselective total synthesis of prostaglandins
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Prostaglandins are among the most important natural isolates owing to their broad range of bioactivities and unique structures. However, current methods for the synthesis of prostaglandins suffer from low yields and lengthy steps. Here, we report a practicability-oriented synthetic strategy for the enantioselective and divergent synthesis of prostaglandins. In this approach, the multiply substituted five-membered rings in prostaglandins were constructed via the key enyne cycloisomerization with excellent selectivity (>20:1 d.r., 98% e.e.). The crucial chiral centre on the scaffold of the prostaglandins was installed using the asymmetric hydrogenation method (up to 98% yield and 98% e.e.). From our versatile common intermediates, a series of prostaglandins and related drugs could be produced in two steps, and fluprostenol could be prepared on a 20-gram scale. [Figure not available: see fulltext.]
- Zhang, Fuhao,Zeng, Jingwen,Gao, Mohan,Wang, Linzhou,Chen, Gen-Qiang,Lu, Yixin,Zhang, Xumu
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p. 692 - 697
(2021/06/01)
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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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- Synthesis of (±) travoprost and its analogs
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A new synthetic approach for the antiglaucoma agent, travoprost (1) has been developed in four steps from key intermediate (2). Key transformations include Horner-Wadsworth-Emmons reaction and separation of diastereomers to obtain (±) travoprost (1) and its analogs.
- Mudduluru, Harikrishna,Hindupur, Rama M.,Dubey, Pramod K.,Madhavaram, Shankar,Tatini, Lakshmikumar,Subbaraju, Gottumukkala V.
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experimental part
p. 234 - 241
(2012/04/18)
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- The tetrahydropyranyl-protected mandelic acid: A novel versatile chiral derivatising agent
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A simple synthesis of (2R)-2-phenyl-2-[(2S)-tetrahydro-2- pyranyloxy]ethanoic acid, a versatile chiral derivatising agent (CDA), is proposed. The derivatisation of secondary alcohols aimed at the absolute configurational assignment, determination of enantiomeric purity as well as semipreparative resolution is described.
- Parve, Omar,Aidnik, Madis,Lille, Uelo,Martin, Ivar,Vallikivi, Imre,Vares, Lauri,Pehk, Tonis
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p. 885 - 896
(2007/10/03)
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- Method for preparing the (+)-isomer of cloprostenol
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The invention relates to a method for preparing the (+)--isomer of cloprostenol of formula I, which is characterized by, (A) regio selective reduction of a protected optically active lactone (-)-isomer of formula II, wherein R is 1-methoxybenzyl,tetrahydropyran-2-yl,4-methoxytetrahydropyran-2-yl or, tetrahydrofuran-2-yl,to the corresponding lactol (-)isomer of formula III, (B) conversion of the lactol (-)-isomer of formula III by reacting with a 4-carboxybutyl-triphenylphosphonium ylide into the corresponding protected optically active (+)-isomer of cloprostenol,and, (C) deprotection of the protected (+)-isomer and isolation of the (+)-isomer of cloprostenol of formula I. This method allows the preparation of the (+)-isomer of cloprostenol at very good yields and with high purity in relatively simple reactions and with use of inexpensive reactants.
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- PROSTANOIDS. XIX. THE SYNTHESIS OF 14C-LABELED CLOPROSTENOL
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A 1:3400 mixture of 2-14C-labelled methyl bromoacetate with the nonradioactive ester gave labelled dimethoxy-2-oxo-3-(m-chlorophenoxy)phosphonate which was used for the synthesis of 16-14C-labelled cloprostenol by the Corey strategy.
- Miftakhov, M. S.,Vostrikov, N. S.,Kuznetsov, O. M.,Kuvatov, Yu. G.,Murinov, Yu. I.,Tolstikov, G. A.
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p. 1072 - 1075
(2007/10/02)
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