Abstract
In vivo phosphorylation of FTY720 (1) in rats and humans resulted exclusively in the biologically active (S)-configured enantiomer, which was proven by an ex vivo o-phthaldialdehyde derivatization protocol especially elaborated for phosphates of 1. Starting from the prochiral amino alcohol 1, racemic and enantiomerically pure phosphates of 1 were synthesized. Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction.
MeSH terms
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Adjuvants, Immunologic / blood*
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Animals
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CHO Cells
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Chromatography, High Pressure Liquid
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Cricetinae
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Cricetulus
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Crystallography, X-Ray
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Fingolimod Hydrochloride
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Humans
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Male
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Organophosphates / blood*
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Organophosphates / chemical synthesis
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Organophosphates / chemistry
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Organophosphates / pharmacology
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Phosphorylation
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Propylene Glycols / blood*
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptors, Lysosphingolipid / agonists
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Receptors, Lysosphingolipid / metabolism
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Sphingosine / analogs & derivatives
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Stereoisomerism
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Structure-Activity Relationship
Substances
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2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl phosphate
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Adjuvants, Immunologic
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Organophosphates
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Propylene Glycols
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Receptors, Lysosphingolipid
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Fingolimod Hydrochloride
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Sphingosine