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Synthesis 2004(5): 641-662  
DOI: 10.1055/s-2004-816003
REVIEW
© Georg Thieme Verlag Stuttgart · New York

Biological Relevance and Synthesis of C-Substituted Morpholine Derivatives

Roel Wijtmansa, Mandy K. S. Vinkb, Hans E. Schoemakerb,c, Floris L. van Delfta, Richard H. Blaauwd, Floris P. J. T. Rutjesa,b
a Department of Organic Chemistry, NSRIM, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Fax: +31(24)365 3393; e-Mail: rutjes@sci.kun.nl;
b Institute of Molecular Chemistry, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands
c DSM Life Science Products, PO Box 18, 6160 MD Geleen, The Netherlands
d Chiralix BV, Toernooiveld 100, 6525 EC Nijmegen, The Netherlands
Further Information

Publication History

Received 16 January 2004
Publication Date:
09 March 2004 (online)

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Abstract

C-Functionalized morpholines are found in a variety of natural products and biologically active compounds, but have also for other reasons been applied in organic synthesis. This review deals with the biological relevance of C-substituted morpholines, their synthesis and important applications in other syntheses.

  • 1 Introduction

  • 2 Biological Relevance of Morpholines

  • 2.1 Naturally Occurring Morpholines

  • 2.2 Bioactive Morpholines

  • 2.2.1 Antidepressants

  • 2.2.2 Appetite Suppressants

  • 2.2.3 Antitumor Activity

  • 2.2.4 Antioxidants

  • 2.2.5 Miscellaneous

  • 3 Morpholine Synthesis

  • 3.1 Synthesis from Amino Alcohols

  • 3.2 Synthesis from Epoxides

  • 3.3 Synthesis via Organometallic Reactions

  • 3.4 Synthesis from Olefins

  • 3.5 Synthesis from Carboxylic Acid Derivatives

  • 3.6 Miscellaneous

  • 4 Morpholines as Synthetic Tools

  • 4.1 The Williams Chiral Auxiliary

  • 4.2 Chiral Auxiliaries

  • 5 Conclusions

Key words

morpholines - heterocycles - medicinal chemistry - asymmetric synthesis - natural products