Synthesis of the Diastereoisomers of 1,2-Dipalmitoyl-57z-glycero-3-thiophosphorylethanolamine and Their Stereospecific Hydrolysis by Phospholipases A2 and C

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

doi:10.1021/bi00256a026

Synthesis of the Diastereoisomers of 1,2-Dipalmitoyl-57z-glycero-3-thiophosphorylethanolamine and Their Stereospecific Hydrolysis by Phospholipases A2 and C

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

Molecular Pharmacology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 PSC13 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 language	English (US)
Pages (from-to)	3202-3206
Number of pages	5
Journal	Biochemistry
Volume	21
Issue number	13
DOIs	https://doi.org/10.1021/bi00256a026
State	Published - Jun 1982

ASJC Scopus subject areas

Biochemistry

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title = "Synthesis of the Diastereoisomers of 1,2-Dipalmitoyl-57z-glycero-3-thiophosphorylethanolamine and Their Stereospecific Hydrolysis by Phospholipases A2 and C",

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 PSC13 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.",

author = "Orr, {George A.} and Brewer, {Curtis F.} and Gayle Heney",

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AU - Brewer, Curtis F.

AU - Heney, Gayle

PY - 1982/6

Y1 - 1982/6

N2 - 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 PSC13 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.

AB - 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 PSC13 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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Synthesis of the Diastereoisomers of 1,2-Dipalmitoyl-57z-glycero-3-thiophosphorylethanolamine and Their Stereospecific Hydrolysis by Phospholipases A2 and C

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