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Synthesis of optically active lipidicα-amino acids and lipidic 2-amino alcohols

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Summary

Lipidicα-amino acids (LAAs) are a class of compounds combining structural features of amino acids with those of fatty acids. They are non-naturalα-amino acids with saturated or unsaturated long aliphatic side chains. Synthetic approaches to optically active LAAs and lipidic 2-amino alcohols (LAALs) are summarized in this review. A general approach to enantioselective synthesis of saturated LAAs 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. Unsaturated LAAs are prepared in their enantiomeric forms by Wittig reactionvia methyl (S)-2di-tert-butoxycarbonylamino-5-oxo-pentanoate. This key intermediate aldehyde is obtained by selective reduction of dimethyl N,N-di-Boc glutamate with DIBAL. (R) or (S) LAALs may be prepared starting from D-mannitol or L-serine. LAAs are converted into LAALs by chemoselective reduction of their fluorides using sodium borohydride with retention of optical purity. Replacement of the hydroxyl group of LAALs by the azido group, followed by selective reduction leads to unsaturated optically active lipidic 1,2-diamines.

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Abbreviations

Bn:

benzyl

Boc:

tert-butoxycarbonyl

DDQ:

2,3-dichloro-5,6-dicyano-1,4-benzoquinone

DET:

diethyl tartrate

DIBAL:

diisobutyl aluminum hydride

DMAP:

4-dimethylaminopyridine

DMF:

N,N-dimethylformamide

DMSO:

dimethyl sulfoxide

EDC:

N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide

Et3N:

triethylamine

HMPA:

hexamethylphosphoramide

HOBt:

1-hydroxybenzotriazole

KN(TMS)2 :

potassium bis(trimethylsilyl)-amide

LAA:

lipidicα-amino acid

LAAAl:

lipidic 2-amino alcohol

LDA:

lipidic 1,2-diamine

LP:

lipidic peptide

MPM-Cl:

p-methoxybenzyl chloride

MsCl:

methanesulphonyl chloride

MTPA:

α-methoxy-α-(trifluoromethyl)phenylaccitc

PLA2 :

phospholipase A2

TBIIP:

tert-butyl hydroperoxide

THF:

tetrahydrofuran

TMSCl:

trimethylsilyl chloride

Tr:

trityl

Z:

benzyloxycarbonyl

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Authors and Affiliations

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

    V. Constantinou-Kokotou

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

    George Kokotos

Authors
  1. V. Constantinou-Kokotou
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  2. George Kokotos
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Constantinou-Kokotou, V., Kokotos, G. Synthesis of optically active lipidicα-amino acids and lipidic 2-amino alcohols. Amino Acids 16, 273–285 (1999). https://doi.org/10.1007/BF01388172

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  • DOI: https://doi.org/10.1007/BF01388172

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