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A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost
Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F(2)α (PGF(2α)) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155834/ https://www.ncbi.nlm.nih.gov/pubmed/28146132 http://dx.doi.org/10.3390/molecules22020217 |
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author | Krupa, Małgorzata Chodyński, Michał Ostaszewska, Anna Cmoch, Piotr Dams, Iwona |
author_facet | Krupa, Małgorzata Chodyński, Michał Ostaszewska, Anna Cmoch, Piotr Dams, Iwona |
author_sort | Krupa, Małgorzata |
collection | PubMed |
description | Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F(2)α (PGF(2α)) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF(2α) analogs 2–5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described. |
format | Online Article Text |
id | pubmed-6155834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61558342018-11-13 A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost Krupa, Małgorzata Chodyński, Michał Ostaszewska, Anna Cmoch, Piotr Dams, Iwona Molecules Article Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F(2)α (PGF(2α)) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF(2α) analogs 2–5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described. MDPI 2017-01-31 /pmc/articles/PMC6155834/ /pubmed/28146132 http://dx.doi.org/10.3390/molecules22020217 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Krupa, Małgorzata Chodyński, Michał Ostaszewska, Anna Cmoch, Piotr Dams, Iwona A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost |
title | A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost |
title_full | A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost |
title_fullStr | A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost |
title_full_unstemmed | A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost |
title_short | A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost |
title_sort | novel convergent synthesis of the potent antiglaucoma agent tafluprost |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155834/ https://www.ncbi.nlm.nih.gov/pubmed/28146132 http://dx.doi.org/10.3390/molecules22020217 |
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