Synthesis of the diastereoisomers of 1,2-dipalmitoyl-sn-glycero-3-thiophosphorylethanolamine and their stereospecific hydrolysis by phospholipases A2 and C

George A. Orr, Curtis F. Brewer, Gayle Heney

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

A convenient three-step synthesis of the phosphorothioate analogue of phosphatidylethanolamine is described. The reaction pathway involves the conversion of a 1,2-diacyl-sn-glycerol to its corresponding thiophosphoric acid dichloride by using PSCl3 in the presence of a tertiary base. Treatment of the dichloride with ethanolamine results in the formation of a cyclic thiophosphoramidate which, upon acidification, undergoes P-N cleavage, giving rise to 1,2-diacyl-sn-glycero-3-thiophosphorylethanolamine. 31P NMR reveals that both diastereoisomers are present in equivalent amounts. It is not possible, however, to separate the two isomers by high-pressure liquid chromatography. 31P NMR and high-pressure liquid chromatography are used to show that phospholipases A2 and C exhibit absolute and opposite stereoselectivity in the hydrolysis of the pair of diastereoisomers.

Original languageEnglish (US)
Pages (from-to)3202-3206
Number of pages5
JournalBiochemistry
Volume21
Issue number13
StatePublished - 1982

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High pressure liquid chromatography
Phospholipases A2
Type C Phospholipases
Hydrolysis
High Pressure Liquid Chromatography
Nuclear magnetic resonance
Stereoselectivity
Ethanolamine
Acidification
Isomers
Glycerol
phosphatidylethanolamine
thiophosphoric acid

ASJC Scopus subject areas

  • Biochemistry

Cite this

Synthesis of the diastereoisomers of 1,2-dipalmitoyl-sn-glycero-3-thiophosphorylethanolamine and their stereospecific hydrolysis by phospholipases A2 and C. / Orr, George A.; Brewer, Curtis F.; Heney, Gayle.

In: Biochemistry, Vol. 21, No. 13, 1982, p. 3202-3206.

Research output: Contribution to journalArticle

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abstract = "A convenient three-step synthesis of the phosphorothioate analogue of phosphatidylethanolamine is described. The reaction pathway involves the conversion of a 1,2-diacyl-sn-glycerol to its corresponding thiophosphoric acid dichloride by using PSCl3 in the presence of a tertiary base. Treatment of the dichloride with ethanolamine results in the formation of a cyclic thiophosphoramidate which, upon acidification, undergoes P-N cleavage, giving rise to 1,2-diacyl-sn-glycero-3-thiophosphorylethanolamine. 31P NMR reveals that both diastereoisomers are present in equivalent amounts. It is not possible, however, to separate the two isomers by high-pressure liquid chromatography. 31P NMR and high-pressure liquid chromatography are used to show that phospholipases A2 and C exhibit absolute and opposite stereoselectivity in the hydrolysis of the pair of diastereoisomers.",
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