---
_id: '11977'
abstract:
- lang: eng
  text: The development of a continuous flow multistep strategy for the synthesis
    of linear peptoids and their subsequent macrocyclization via Click chemistry is
    described. The central transformation of this process is an Ugi four-component
    reaction generating the peptidomimetic core structure. In order to avoid exposure
    to the often toxic and malodorous isocyanide building blocks, the continuous approach
    was telescoped by the dehydration of the corresponding formamide. In a concurrent
    operation, the highly energetic azide moiety required for the subsequent intramolecular
    copper-catalyzed azide–alkyne cycloaddition (Click reaction) was installed by
    nucleophilic substitution from a bromide precursor. All steps yielding to the
    linear core structures can be conveniently coupled without the need for purification
    steps resulting in a single process generating the desired peptidomimetics in
    good to excellent yields within a 25 min reaction time. The following macrocyclization
    was realized in a coil reactor made of copper without any additional additive.
    A careful process intensification study demonstrated that this transformation
    occurs quantitatively within 25 min at 140 °C. Depending on the resulting ring
    strain, either a dimeric or a monomeric form of the cyclic product was obtained.
article_processing_charge: No
article_type: original
author:
- first_name: Carlos Eduardo M.
  full_name: Salvador, Carlos Eduardo M.
  last_name: Salvador
- first_name: Bartholomäus
  full_name: Pieber, Bartholomäus
  id: 93e5e5b2-0da6-11ed-8a41-af589a024726
  last_name: Pieber
  orcid: 0000-0001-8689-388X
- first_name: Philipp M.
  full_name: Neu, Philipp M.
  last_name: Neu
- first_name: Ana
  full_name: Torvisco, Ana
  last_name: Torvisco
- first_name: Carlos
  full_name: Kleber Z. Andrade, Carlos
  last_name: Kleber Z. Andrade
- first_name: C. Oliver
  full_name: Kappe, C. Oliver
  last_name: Kappe
citation:
  ama: Salvador CEM, Pieber B, Neu PM, Torvisco A, Kleber Z. Andrade C, Kappe CO.
    A sequential Ugi multicomponent/Cu-catalyzed azide–alkyne cycloaddition approach
    for the continuous flow generation of cyclic peptoids. <i>The Journal of Organic
    Chemistry</i>. 2015;80(9):4590-4602. doi:<a href="https://doi.org/10.1021/acs.joc.5b00445">10.1021/acs.joc.5b00445</a>
  apa: Salvador, C. E. M., Pieber, B., Neu, P. M., Torvisco, A., Kleber Z. Andrade,
    C., &#38; Kappe, C. O. (2015). A sequential Ugi multicomponent/Cu-catalyzed azide–alkyne
    cycloaddition approach for the continuous flow generation of cyclic peptoids.
    <i>The Journal of Organic Chemistry</i>. American Chemical Society. <a href="https://doi.org/10.1021/acs.joc.5b00445">https://doi.org/10.1021/acs.joc.5b00445</a>
  chicago: Salvador, Carlos Eduardo M., Bartholomäus Pieber, Philipp M. Neu, Ana Torvisco,
    Carlos Kleber Z. Andrade, and C. Oliver Kappe. “A Sequential Ugi Multicomponent/Cu-Catalyzed
    Azide–Alkyne Cycloaddition Approach for the Continuous Flow Generation of Cyclic
    Peptoids.” <i>The Journal of Organic Chemistry</i>. American Chemical Society,
    2015. <a href="https://doi.org/10.1021/acs.joc.5b00445">https://doi.org/10.1021/acs.joc.5b00445</a>.
  ieee: C. E. M. Salvador, B. Pieber, P. M. Neu, A. Torvisco, C. Kleber Z. Andrade,
    and C. O. Kappe, “A sequential Ugi multicomponent/Cu-catalyzed azide–alkyne cycloaddition
    approach for the continuous flow generation of cyclic peptoids,” <i>The Journal
    of Organic Chemistry</i>, vol. 80, no. 9. American Chemical Society, pp. 4590–4602,
    2015.
  ista: Salvador CEM, Pieber B, Neu PM, Torvisco A, Kleber Z. Andrade C, Kappe CO.
    2015. A sequential Ugi multicomponent/Cu-catalyzed azide–alkyne cycloaddition
    approach for the continuous flow generation of cyclic peptoids. The Journal of
    Organic Chemistry. 80(9), 4590–4602.
  mla: Salvador, Carlos Eduardo M., et al. “A Sequential Ugi Multicomponent/Cu-Catalyzed
    Azide–Alkyne Cycloaddition Approach for the Continuous Flow Generation of Cyclic
    Peptoids.” <i>The Journal of Organic Chemistry</i>, vol. 80, no. 9, American Chemical
    Society, 2015, pp. 4590–602, doi:<a href="https://doi.org/10.1021/acs.joc.5b00445">10.1021/acs.joc.5b00445</a>.
  short: C.E.M. Salvador, B. Pieber, P.M. Neu, A. Torvisco, C. Kleber Z. Andrade,
    C.O. Kappe, The Journal of Organic Chemistry 80 (2015) 4590–4602.
date_created: 2022-08-25T10:52:24Z
date_published: 2015-05-01T00:00:00Z
date_updated: 2023-02-21T10:10:04Z
day: '01'
doi: 10.1021/acs.joc.5b00445
extern: '1'
external_id:
  pmid:
  - '25842982'
intvolume: '        80'
issue: '9'
language:
- iso: eng
month: '05'
oa_version: None
page: 4590-4602
pmid: 1
publication: The Journal of Organic Chemistry
publication_identifier:
  eissn:
  - 1520-6904
  issn:
  - 0022-3263
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: A sequential Ugi multicomponent/Cu-catalyzed azide–alkyne cycloaddition approach
  for the continuous flow generation of cyclic peptoids
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 80
year: '2015'
...