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Chemical Synthesis of Heparin Fragments and Analogues

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Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products

Abstract

The history of heparin dates back to 1916 when Jay Maclean, a PhD student in Howell’s laboratory, isolated an anticoagulant substance instead of the expected procoagulant phospholipids (1, 2). Since this substance was extracted from liver it was named heparin, in 1918, by Howell and Holt. Several years of debate then followed about the chemical nature of heparin (3). While it was initially thought to be a phospholipid, the polysaccharidic nature of heparin was suspected in 1925 and confirmed in the following years. However, the high complexity of the compound and the paucity of the analytical tools then available resulted in a very intricate situation where several authors proposed conflicting hypotheses regarding the nature of the different monosaccharides present as well as their substituents. It was only in the late 1960’s that the currently accepted chemical structure of heparin could be established (for a review, see (4)).

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Abbreviations

All:

allyl

Ac:

acetyl

Bn:

benzyl

Me:

methyl

Z:

benzyloxycarbonyl

tBu:

ter-butyl

MCA:

monochloroacetyl

Lev:

levulinoyl

Tf:

trifluoromethylsulphonyl

Ph:

phenyl

TBDMS:

tert-butyldimethylsilyl

THP:

tetrahydropyranlyl

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Authors and Affiliations

  1. Sanofi Recherche, Gentilly, France

    M. Petitou

  2. Organon Scientific Development Group, Oss, The Netherlands

    C. A. A. van Boeckel

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  1. M. Petitou
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  2. C. A. A. van Boeckel
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Editor information

Editors and Affiliations

  1. Department of Chemistry, The Florida State University, Tallahassee, Florida, USA

    W. Herz

  2. Chemistry Department, The University, Glasgow, Scotland

    G. W. Kirby

  3. Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, USA

    R. E. Moore

  4. Institut für Organische Chemie und Biochemie, Universität Bonn, Bonn, Federal Republic of Germany

    W. Steglich

  5. Institut für Organische Chemie, Universität Basel, Basel, Switzerland

    Ch. Tamm

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Petitou, M., van Boeckel, C.A.A. (1992). Chemical Synthesis of Heparin Fragments and Analogues. In: Herz, W., Kirby, G.W., Moore, R.E., Steglich, W., Tamm, C. (eds) Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products. Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products, vol 60. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9225-2_2

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