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Synthesis 2023; 55(03): 499-509
DOI: 10.1055/a-1915-7794
paper

Stereospecific Synthesis of Substituted Sulfamidates as Privileged Morpholine Building Blocks

Uros Stojiljkovic‡
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
b   University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056 Basel, Switzerland
,
Claudio Meyer‡
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
b   University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056 Basel, Switzerland
,
Pierre Boulay‡
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
,
Paul Hebeisen
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
,
Denise Rageot
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
,
Matthias P. Wymann  ∗
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
,
Chiara Borsari  ∗
a   University of Basel, Department of Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland
› Author AffiliationsThis work was supported by the Swiss National Science Foundation (Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; grants 310030_153211, 316030_133860, 316030_198526 and 200021_204602); a Swiss Cancer Research Foundation grant (KFS-5442-08-2021) and a Stiftung für Krebsbekämpfung (grant 341; to M.P.W.).
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Abstract

Morpholine is a heterocyclic moiety that is widely used in medicinal chemistry as a building block. It has unique physicochemical properties, as it can improve both pharmacokinetic and pharmacodynamic properties of active pharmaceutical ingredients. However, the efficient synthesis of enantiomerically pure morpholine building blocks remains challenging. Herein, we report the synthesis of optically pure 3-hydroxymethylmorpholine building blocks, as well as their sulfamidates, exploiting a stereospecific strategy from chiral pool material.

Key words

morpholines - sulfamidates - stereoselectivity - chiral building blocks - privileged scaffolds

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1915-7794.
  • Supporting Information


Publication History

Received: 22 June 2022

Accepted after revision: 02 August 2022

Accepted Manuscript online:
02 August 2022

Article published online:
10 October 2022

© 2022. Thieme. All rights reserved

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