- Asymmetric Synthesis of Corey Lactone and Latanoprost
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Corey lactone was synthesized in a single pot within 152 minutes in a 50 % overall yield via pot and time economical manner. Latanoprost, an antiglaucoma blockbuster drug, was also synthesized via seven pot reaction with five purifications in a 25 % total yield. One of the key reactions is asymmetric domino Michael/Michael reaction, formal [3+2] cycloaddition reaction, of 3-(dimethylphenylsilyl)propenal and ethyl 4-oxo-2-pentenoate, catalyzed by diphenylprolinol silyl ether, which constructed the core substituted cyclopentanone derivative with nearly optically pure form.
- Hayashi, Yujiro,Umekubo, Nariyoshi
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supporting information
p. 6221 - 6227
(2020/09/21)
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- Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer–Villiger Oxidation
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A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer–Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey′s route. Furthermore, the reactivity and enantioselectivity of B-V oxidation of racemic bicyclic cyclobutanones were evaluated and 90–99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone-containing natural products to promote drug discovery.
- Zhu, Kejie,Hu, Sha,Liu, Minjie,Peng, Haihui,Chen, Fen-Er
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p. 9923 - 9927
(2019/05/16)
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- Secondary compounds in the catalytic hydrogenation of enone and allylic alcohol prostaglandin intermediates: Isolation, characterization, and X-ray crystallography
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The discovery of the intraocular pressure reduction of 13,14-hydrogenated prostaglandins, among which Latanoprost is the most used drug in glaucoma treatment, has stimulated researchers to improve the synthesis of prostaglandins and their structural analo
- Tǎnase, Constantin I.,Cocu, Florea,Drǎghici, Constantin,Hanganu, Anamaria,Pintilie, Lucia,Maganu, Maria,Munteanu, Cristian V. A.,Shova, Sergiu
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p. 7582 - 7599
(2019/05/27)
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- An improved synthesis of latanoprost involving effective control on 15(S) diastereomer
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An improved process for the synthesis of latanoprost having excellent optical purity (de 99.9%, [α]D20 = +35.37° (c = 0.90, acetonitrile)) without use of preparative HPLC is described. This process involves effective purification of hydroxyl intermediate (5A) through solvent crystallization followed by inhibition of inversion of the chiral center at C-15 position. This was possible due to judicious use of diol intermediate (6) for double bond reduction prior to hydroxyl protection.
- Sasane, Sachin A.,Bhise, Nandu B.,Singh, Girij P.,Joseph, Alex,Shenoy, Gautham G.
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p. 2350 - 2356
(2019/07/31)
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- PROCESSES AND INTERMEDIATES FOR THE PREPARATIONS OF PROSTAGLANDINS
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A method for preparing cyclopentanones or lactones is provided to be useful for preparation of prostagladins, to remove problems such as the long synthesis route and the removal of undesired isomers, and thus achieves a simple and economical synthesis route. The method for preparing a compound of the following formula II having an enantiomer purity higher than 95% e.e.(enantiomeric excess) comprises the steps of: reacting a compound of the following formula IV having an optical purity higher than 90% e.e. with cuprate; and optionally performing a de-protection reaction of the obtained compound to convert P1, P2, or both P1 and P2 into H. In the formulae, Z does not take part in coupling and de-protection reactions and is an optional group acting as a leaving group in reduction/lactonization reactions, R2 is a single bond, C1-4 alkylene or -CH2O- group, R3 is a C1-7-alkyl or aryl or aralkyl unsubstituted or substituted by C1-4 alkyl, halogen or trihalomethyl, X1 and X2 are independently hydrogen or P1 and P2, respectively, wherein P1 and P2 are protective groups for hydroxyl groups which are identical to or different from each other.
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Paragraph 0230; 0231; 0272; 0273
(2017/01/05)
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- Improved Process for the Production of Prostaglandins and Prostaglandin Analogs
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The present invention relates to an improved process for the production of prostaglandins and prostaglandin analogs. In particular, this invention relates to the production of prostaglandins of the PGF2α-series, including latanoprost, travoprost, and bimatoprost, which are active pharmaceutical ingredients used for the reduction of elevated intraocular pressure in patients with glaucoma and ocular hypertension.
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Page/Page column 54-55
(2010/01/29)
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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 15
(2010/11/03)
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- Method for preparing prostaglandin F analogue
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A method for preparing a prostaglandin F analogue represented by the following formula (I) is disclosed, wherein R1, and are as defined in the specification.
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Page/Page column 10
(2009/10/21)
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- Method for preparing prostaglandin derivative
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A method for preparing a prostaglandin derivative represented by the following general formula (I): (wherein Ph represents phenyl group, R1 represents a C1-7 alkyl group, a C1-7 alkenyl group, phenyl group, or benzyl group), which comprises the successive steps (1) to (8) described in the specification, or any one step or two or more successive steps selected from the group consisting of the steps (1) to (8). A method for efficiently, inexpensively and safely preparing prostaglandin derivatives, of which typical example is latanoprost, is provided.
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Page/Page column 9
(2008/06/13)
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- METHOD FOR PREPARING PROSTAGLANDIN DERIVATIVE
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A method for preparing a prostaglandin derivative represented by the following general formula (I): (wherein Ph represents phenyl group, R1 represents a C1-7 alkyl group, a C1-7 alkenyl group, phenyl group, or benzyl group), which comprises the successive steps (1) to (8) described in the specification, or any one step or two or more successive steps selected from the group consisting of the steps (1) to (8). A method for efficiently, inexpensively and safely preparing prostaglandin derivatives, of which typical example is latanoprost, is provided.
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Page/Page column 6
(2008/06/13)
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- Processes and intermediates for the preparations of prostaglandins
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The present invention provides novel processes for the preparation of a cyclopentanone of Formula II and a lactone of Formula I, which are useful in the production of prostaglandins: wherein Z, R2, R3, X1, X2, and are as defined in the specification. The invention also provides novel enantiomerically enriched compounds.
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Page/Page column 14
(2008/06/13)
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- Processes and intermediates for the preparations of prostaglandins
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The present invention provides novel processes for the preparation of a cyclopentanone of Formula II and a lactone of Formula I, which are useful in the production of prostaglandins: wherein Z, R2, R3, X1, X2, and ------------ are as defined in the specification. The invention also provides novel enantiomerically enriched compounds.
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Page/Page column 20-21
(2010/11/28)
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- Method and intermediate for preparing a prostaglandin F-type compound
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A method for preparing a prostaglandin F-type compound. Also disclosed is an intermediate of the following formula (II) compound wherein R′, X and A have the same meaning as given in the specification.
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Page/Page column 13
(2010/10/20)
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- Ligand-controlled palladium-catalyzed intramolecular reactions of phenyl-substituted prostaglandin P(2α) analogues
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Palladium catalyzed intramolecular cyclization of the 15R and 15S epimers of 17-(2-iodophenyl)-18,19,20-trinorprostaglandin F(2α) isopropylester [(15R)-5 and (15S)-5, respectively] produce a complex mixture of products including various tetrahydronaphthol
- Liljebris,Resul,Hacksell
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p. 9139 - 9154
(2007/10/02)
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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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