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Synthesis of medicinally useful lipidicα-amino acids, 2-amino alcohols and diamines

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Summary

The lipidicα-amino acids (LAAs) are non-naturalα-amino acids with saturated or unsaturated long aliphatic side chains. LAAs and their derivatives (lipid mimetics) together with the lipidic peptides represent a class of compounds which combine structural features of lipids with those of amino acids and peptides. Racemic LAAs may be prepared by classical methods and resolved by chemical or enzymatic methods. LAA amides and esters with saturated or unsaturated long chain amines and alcohols respectively, as well as lipidic dipeptide derivatives inhibit both pancreatic and human platelet phospholipase A2. Lipophilic peptide derivatives are inhibitors of human neutrophil elastase. LAAs and their oligomers have been used as drug delivery system. A Lipid-Core-Peptide system has been designed and used as a combined adjuvant-carrier-vaccine system. A variety of lipid mimetics such as lipidic 2-amino alcohols, lipidic 1,2- and 1,3-diamines have been prepared based upon LAAs. Some of them are potent inhibitors of phospholipase A2. A general approach to enantioselective synthesis of LAAs and lipid mimetics is based on the oxidative cleavage of 3-amino-1,2-diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols.

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Abbreviations

Boc:

tert-butoxycarbonyl

BSA:

bovine serum albumin

CD:

circular dichroism

DET:

diethyl tartrate

DIBAL:

diisobutyl aluminum hydride

DMF:

N,N-dimethylformammide

HMPA:

hexamethylphosphoramide

HNE:

human neutophil elastase

LAA:

lipidic amino acid

LAAL:

lipidic amino alcohol

LH-RH:

luteinizing hormone-releasing hormone

LCP:

lipid-core-peptide

LDA:

lipidic diamine

LP:

lipidic peptide

MAP:

multiple antigenic peptide

PLA2 :

phospholipase A2

TBHP:

tert-butyl hydroperoxide

THF:

tetrahydrofuran

TRH:

thyrotropin-releasing hormone

Z:

benzyloxycarbonyl

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Authors and Affiliations

  1. Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, GR-15771, Athens, Greece

    G. Kokotos

  2. Instituto Universitario de Bio-Organica “Antonio Gonzalez”, Universidad de La Laguna, Tenerife, Spain

    V. Martin

  3. Chemistry Laboratory, Agricultural University of Athens, Athens, Greece

    V. Constantinou-Kokotou

  4. University-Industry Centre for Pharmaceutical Research, The School of Pharmacy, University of London, London, England

    W. A. Gibbons

Authors
  1. G. Kokotos
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  2. V. Martin
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  3. V. Constantinou-Kokotou
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  4. W. A. Gibbons
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Kokotos, G., Martin, V., Constantinou-Kokotou, V. et al. Synthesis of medicinally useful lipidicα-amino acids, 2-amino alcohols and diamines. Amino Acids 11, 329–343 (1996). https://doi.org/10.1007/BF00807940

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  • DOI: https://doi.org/10.1007/BF00807940

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