Next Article in Journal
Exploring the Effects of Geographical Origin on the Chemical Composition and Quality Grading of Vitis vinifera L. cv. Chardonnay Grapes
Previous Article in Journal
In Situ Coupling of Ultrasound to Electro- and Photo-Deposition Methods for Materials Synthesis
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(2), 217; doi:10.3390/molecules22020217

A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost

1
Chemistry Department, Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland
2
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 42/52, 01-224 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Received: 5 December 2016 / Accepted: 25 January 2017 / Published: 31 January 2017
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [1336 KB, uploaded 6 February 2017]   |  

Abstract

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) 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 PGF2α 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. View Full-Text
Keywords: tafluprost; prostaglandins; Corey lactone; Julia–Lythgoe olefination; fluorination tafluprost; prostaglandins; Corey lactone; Julia–Lythgoe olefination; fluorination
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Krupa, M.; Chodyński, M.; Ostaszewska, A.; Cmoch, P.; Dams, I. A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost. Molecules 2017, 22, 217.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top