Synthesis of 4-aminotetrahydropyran scaffolds for drug discovery

Andrew Nortcliffe; Gavin D S Milne; Daniel Hamza; Christopher J Moody

doi:10.1016/j.bmc.2017.02.039

Synthesis of 4-aminotetrahydropyran scaffolds for drug discovery

Bioorg Med Chem. 2017 Apr 1;25(7):2218-2225. doi: 10.1016/j.bmc.2017.02.039. Epub 2017 Feb 24.

Authors

Andrew Nortcliffe¹, Gavin D S Milne², Daniel Hamza², Christopher J Moody³

Affiliations

¹ School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
² Sygnature Discovery Ltd, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK.
³ School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: c.j.moody@nottingham.ac.uk.

PMID: 28279558
DOI: 10.1016/j.bmc.2017.02.039

Abstract

Functionalised tetrahydropyran scaffolds were prepared using a tethered enol-ether Prins cyclisation and elaborated to show their potential use in library synthesis. The key 4-hydroxytetrahydropyran scaffold could be readily manipulated to the 4-azidotetrahydropyran that could be elaborated via copper catalysed azide-alkyne cycloaddition or by reduction to the amine, to provide sp³-rich scaffolds useful for drug discovery.

Keywords: Amine functionalisation; Azide-alkyne cycloaddition; Prins cyclisation; Tetrahydropyran.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cyclization
Drug Discovery*
Furans / chemical synthesis
Furans / chemistry*

Substances

Furans
tetrahydrofuran