A Continuous Flow Strategy for the Facile Synthesis and Elaboration of Semi-Saturated Heterobicyclic Fragments

Nicola Luise, Eleanor W. Wyatt, Gary Tarver, Paul Wyatt (Lead / Corresponding author)

Research output: Contribution to journalArticle

Abstract

An efficient hydrogenation protocol under continuous flow conditions was developed for the synthesis of underrepresented semi-saturated bicyclic fragments containing highly sp 3-rich skeletons for fragment-based drug discovery (FBDD) programs. Excellent yields were generally achieved by using Pd/C (10 % w/w) and RaNi at 25–150 °C under 4–100 bar of hydrogen pressure. The generated fragments, with appropriate physicochemical properties, present diverse hydrogen-bonding pharmacophores and useful vectors for their synthetic elaboration in the optimization stage. Successive, simple functionalizations in continuous flow were accomplished to demonstrate the opportunity to develop multi-step continuous flow synthesis of valuable starting points for FBDD campaigns. A conclusive quality control (QC) was essential to discard those structures which do not fit the typical fragment library parameters.

Original languageEnglish
Pages (from-to)1341-1349
Number of pages9
JournalEuropean Journal of Organic Chemistry
Volume2019
Issue number6
Early online date7 Jan 2019
DOIs
Publication statusPublished - 14 Feb 2019

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fragments
synthesis
Hydrogenation
Quality control
Hydrogen
Hydrogen bonds
drugs
hydrogen
quality control
musculoskeletal system
hydrogenation
Drug Discovery
optimization

Keywords

  • Drug discovery
  • Flow reactions
  • Fused-ring systems
  • Heterocycles
  • Hydrogenation

Cite this

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A Continuous Flow Strategy for the Facile Synthesis and Elaboration of Semi-Saturated Heterobicyclic Fragments. / Luise, Nicola; Wyatt, Eleanor W.; Tarver, Gary; Wyatt, Paul (Lead / Corresponding author).

In: European Journal of Organic Chemistry, Vol. 2019, No. 6, 14.02.2019, p. 1341-1349.

Research output: Contribution to journalArticle

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