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Grant support

Funding of this project by the Spanish MINECO, grant No. RTI2018-095588-B-I00 (Co-funded by the European Regional Development Fund/European Social Fund, Investing in your future) and FUSP-CEU (PC17/17) is acknowledged. J. G. thanks the Fundacion San Pablo-CEU for a pre-doctoral fellowship.

Analysis of institutional authors

García-Lacuna JAuthorDomínguez GAuthorPérez-Castells JCorresponding Author

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November 1, 2019
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Synthesis of treprostinil: key Claisen rearrangement and catalytic Pauson-Khand reactions in continuous flow

Publicated to:Organic & Biomolecular Chemistry. 17 (43): 9489-9501 - 2019-11-21 17(43), DOI: 10.1039/c9ob02124h

Authors: Garcia-Lacuna, Jorge; Dominguez, Gema; Blanco-Urgoiti, Jaime; Perez-Castells, Javier

Affiliations

CSFlowChem SL, C Boadilla Camino 3, Madrid 28050, Spain - Author
Univ San Pablo CEU, Fac Farm, Dept Quim & Bioquim, Madrid 28668, Spain - Author

Abstract

A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson-Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection-deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin.

Keywords

ChemistryLiquidProcess windowsReactorsSafe

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Organic & Biomolecular Chemistry due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 13/57, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Organic.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-07-18:

  • WoS: 7
  • Scopus: 8
  • Europe PMC: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 19.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 19 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (García Lacuna, Jorge) and Last Author (PEREZ CASTELLS, JAVIER).

the author responsible for correspondence tasks has been PEREZ CASTELLS, JAVIER.