eprintid: 10090628
rev_number: 31
eprint_status: archive
userid: 608
dir: disk0/10/09/06/28
datestamp: 2020-01-31 14:45:50
lastmod: 2021-12-27 23:07:43
status_changed: 2020-01-31 14:45:50
type: article
metadata_visibility: show
creators_name: Picken, C
creators_name: Laing, P
creators_name: Shen, L
creators_name: Clapp, LH
creators_name: Brocchini, S
title: Synthetic routes to treprostinil N-acyl methylsulfonamide
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G08
divisions: D14
divisions: GA2
keywords: Prostacyclin, Treprostinil, Acylsulfonamide, Prodrug
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: The synthesis of the prodrug candidate, treprostinil N-acyl methylsulfonamide 5 was accomplished from treprostinil 2 utilising protecting group strategies. A more direct synthesis for the prodrug was also achieved using a treprostinil triol precursor 12 and bromoacetyl acylmethylsulfonamide 14. The overall yield of treprostinil N-acyl sulfonamide 5 directly from the triol precursor 12 is similar to the protecting group strategies because deprotonation of the acidic proton in the bromoacetyl acylmethylsulfonamide 14 reduces electrophilicity. However, the more direct route using the treprostinil triol precursor holds greater promise as a strategy to prepare a wide range of treprostinil prodrug candidates. Treprostinil N-acyl methylsulfonamide prodrug 5 exhibited a 30-fold decrease in the potency at the human prostacyclin (IP) receptor compared to treprostinil 2 in an in vitro cyclic AMP assay.
date: 2020-01-30
date_type: published
official_url: https://doi.org/10.1016/j.tetlet.2019.151428
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1733273
doi: 10.1016/j.tetlet.2019.151428
lyricists_name: Brocchini, Steve
lyricists_name: Clapp, Lucie
lyricists_id: SBROC55
lyricists_id: LCLAP60
actors_name: Dewerpe, Marie
actors_id: MDDEW97
actors_role: owner
full_text_status: public
publication: Tetrahedron Letters
volume: 61
number: 5
article_number: 151428
citation:        Picken, C;    Laing, P;    Shen, L;    Clapp, LH;    Brocchini, S;      (2020)    Synthetic routes to treprostinil N-acyl methylsulfonamide.                   Tetrahedron Letters , 61  (5)    , Article 151428.  10.1016/j.tetlet.2019.151428 <https://doi.org/10.1016/j.tetlet.2019.151428>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10090628/9/Clapp_Picken%20et%20al_manuscript_clean_cp.pdf