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

Journal Article · Fri Sep 01 04:00:00 UTC 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), Journal Name: Lipids; (USA) Vol. 24:9; ISSN LPDSA; ISSN 0024-4201
• Country of Publication: United States
• Language: English

Related Subjects

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