A novel convergent synthesis of the potent antiglaucoma agent travoprost
The 16-(3-trifluoromethyl)phenoxy PGF2α analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF2α analogues was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enanti...
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Veröffentlicht in: | Tetrahedron 2013-02, Vol.69 (5), p.1634-1648 |
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container_title | Tetrahedron |
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creator | Dams, Iwona Chodyński, Michał Krupa, Małgorzata Pietraszek, Anita Zezula, Marta Cmoch, Piotr Kosińska, Monika Kutner, Andrzej |
description | The 16-(3-trifluoromethyl)phenoxy PGF2α analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF2α analogues was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enantiomerically pure aldehyde ω-chain synthon (S)-(−)-16a. Subsequent hydrolysis of protecting groups and final esterification of fluprostenol (7a) yielded travoprost (8a). The main advantages are the preparation of high purity travoprost (8a) and the application of comparatively cheap reagents. The novel convergent strategy allows the synthesis of a whole series of 13,14-en-15-ol PGF2α analogues from a common and structurally advanced prostaglandin intermediate 15. The preparation and identification of two synthetic impurities, 15-epi isomer (8b) of travoprost and a new prostaglandin related ester (5Z)-(+)-18, are also described.
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doi_str_mv | 10.1016/j.tet.2012.11.087 |
format | Article |
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[Display omitted]</description><subject>Aldehydes</subject><subject>Analogue</subject><subject>Corey lactone</subject><subject>Esters</subject><subject>Hydrolysis</subject><subject>Isomers</subject><subject>Nucleophilic addition</subject><subject>Prostaglandins</subject><subject>Strategy</subject><subject>Synthesis</subject><subject>Tetrahedrons</subject><subject>Travoprost</subject><issn>0040-4020</issn><issn>1464-5416</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkE1PwzAMhiMEEuPjB3DrkUuLnWRpK07TBAxpEhc4R2nmjk5dM5Ks0v49GeMMJ1vW89ryw9gdQoGA6mFTRIoFB-QFYgFVecYmKJXMpxLVOZsASMglcLhkVyFsAACRiwlbzLLBjdRn1g0j-TUNMQuHIX5S6ELm2ix12c7F49wMsVv3Zm_d1mTmB43ejG7nXYg37KI1faDb33rNPp6f3ueLfPn28jqfLXMrlIi5rWwlrZBQN7aFxnBZQqUq3rStFVwQNFSBECsjypZPjRIG-UqgtdI2rVSVuGb3p73p6teeQtTbLljqezOQ2weNpUxYjXX5PyrqugZZlSqheEJt-iV4avXOd1vjDxpBHwXrjU6C9VGwRtRJcMo8njKU3h078jrYjgZLq86TjXrluj_S33cpg9M</recordid><startdate>20130204</startdate><enddate>20130204</enddate><creator>Dams, Iwona</creator><creator>Chodyński, Michał</creator><creator>Krupa, Małgorzata</creator><creator>Pietraszek, Anita</creator><creator>Zezula, Marta</creator><creator>Cmoch, Piotr</creator><creator>Kosińska, Monika</creator><creator>Kutner, Andrzej</creator><general>Elsevier Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7U5</scope><scope>L7M</scope></search><sort><creationdate>20130204</creationdate><title>A novel convergent synthesis of the potent antiglaucoma agent travoprost</title><author>Dams, Iwona ; Chodyński, Michał ; Krupa, Małgorzata ; Pietraszek, Anita ; Zezula, Marta ; Cmoch, Piotr ; Kosińska, Monika ; Kutner, Andrzej</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-c8c84c3409bcf0ba24708682bffc323e0be8033da37f25a63a12d31cc4cbf4683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aldehydes</topic><topic>Analogue</topic><topic>Corey lactone</topic><topic>Esters</topic><topic>Hydrolysis</topic><topic>Isomers</topic><topic>Nucleophilic addition</topic><topic>Prostaglandins</topic><topic>Strategy</topic><topic>Synthesis</topic><topic>Tetrahedrons</topic><topic>Travoprost</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dams, Iwona</creatorcontrib><creatorcontrib>Chodyński, Michał</creatorcontrib><creatorcontrib>Krupa, Małgorzata</creatorcontrib><creatorcontrib>Pietraszek, Anita</creatorcontrib><creatorcontrib>Zezula, Marta</creatorcontrib><creatorcontrib>Cmoch, Piotr</creatorcontrib><creatorcontrib>Kosińska, Monika</creatorcontrib><creatorcontrib>Kutner, Andrzej</creatorcontrib><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Tetrahedron</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dams, Iwona</au><au>Chodyński, Michał</au><au>Krupa, Małgorzata</au><au>Pietraszek, Anita</au><au>Zezula, Marta</au><au>Cmoch, Piotr</au><au>Kosińska, Monika</au><au>Kutner, Andrzej</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel convergent synthesis of the potent antiglaucoma agent travoprost</atitle><jtitle>Tetrahedron</jtitle><date>2013-02-04</date><risdate>2013</risdate><volume>69</volume><issue>5</issue><spage>1634</spage><epage>1648</epage><pages>1634-1648</pages><issn>0040-4020</issn><eissn>1464-5416</eissn><abstract>The 16-(3-trifluoromethyl)phenoxy PGF2α analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF2α analogues was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enantiomerically pure aldehyde ω-chain synthon (S)-(−)-16a. Subsequent hydrolysis of protecting groups and final esterification of fluprostenol (7a) yielded travoprost (8a). The main advantages are the preparation of high purity travoprost (8a) and the application of comparatively cheap reagents. The novel convergent strategy allows the synthesis of a whole series of 13,14-en-15-ol PGF2α analogues from a common and structurally advanced prostaglandin intermediate 15. The preparation and identification of two synthetic impurities, 15-epi isomer (8b) of travoprost and a new prostaglandin related ester (5Z)-(+)-18, are also described.
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subjects | Aldehydes Analogue Corey lactone Esters Hydrolysis Isomers Nucleophilic addition Prostaglandins Strategy Synthesis Tetrahedrons Travoprost |
title | A novel convergent synthesis of the potent antiglaucoma agent travoprost |
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