Synthesis of trideuterated O-alkyl platelet activating factor and lyso derivatives

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Lipids; (USA)

DOI:https://doi.org/10.1007/BF02544585· OSTI ID:5085597

Prakash, C; Saleh, S; Taber, D F; Blair, I A ^[1]

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1. Vanderbilt Univ., Nashville, TN (USA)

Racemic heavy isotope analogs of 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF) and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were prepared for use as internal standards to facilitate quantitative studies based on mass spectrometry. Starting from pentadecane-1,15-diol and rac-glycerol-1,2-acetonide, a convergent synthesis of 1-O-(16'-2H3)hexadecyl and 1-O-(18'-2H3)octadecyl rac-glycero-3-phosphocholine and their acetyl derivatives is described. Three deuterium atoms were introduced at the terminal position of the 1-O-alkyl group by displacement of the p-toluensulfonyl group from 1-O-alkyl-15'-p-toluensulfonate and 1-O-alkyl-17'-p-toluensulfonate with (2H3)-methylmagnesium iodide. The 1-O-alkyl-17'-p-toluensulfonate was obtained by reaction of the 1-O-alkyl-15'-p-toluensulfonate with allylmagnesium bromide, followed by reductive ozonolysis and treatment with p-toluene-sulfonyl chloride. The hydroxyl group at C-2 was protected by a benzyl group and removed at a late stage in the synthesis. This provided the corresponding lyso-derivatives or allowed preparation of racemic PAF by subsequent acetylation of the free hydroxy group. The phosphocholine moiety was introduced at glycerol C-3 by reaction with bromoethyldichlorophosphate and trimethylamine. The synthetic compounds were analyzed by FAB/MS and GC/NICIMS. They were shown to contain less than 0.6% protium impurity.

• OSTI ID: 5085597
• Journal Information: Lipids; (USA), Vol. 24:9; ISSN 0024-4201
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BLOOD COAGULATION FACTORS
BIOSYNTHESIS
ACETYLATION
DEUTERIUM
GAS CHROMATOGRAPHY
MASS SPECTROSCOPY
PHOSPHOLIPIDS
TRACER TECHNIQUES
ACYLATION
CHEMICAL REACTIONS
CHROMATOGRAPHY
COAGULANTS
DRUGS
ESTERS
HEMATOLOGIC AGENTS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PROTEINS
SEPARATION PROCESSES
SPECTROSCOPY
STABLE ISOTOPES
SYNTHESIS
550201* - Biochemistry- Tracer Techniques