title: A new synthesis of lysophosphatidylcholines and related derivatives. Use of p-toluenesulfonate for hydroxyl group protection.
abstract: A new stereoselective synthesis of lysophosphatidylcholines is reported. The synthesis is based upon (1) the use of 3-p-toluenesulfonyl-sn-glycerol to provide the stereocenter for construction of the optically active lysophospholipid molecule, (2) tetrahydropyranylation of the secondary alcohol function to achieve orthogonal protection of the sn-2- and sn-3-glycerol positions, and (3) elaboration of the phosphodiester headgroup using a 2-chloro-1,3,2-dioxaphospholane/trimethylamine sequence. In the course of developing the synthesis it has been discovered that methoxyacetate displacement of the sn-3-p-toluenesulfonate yields a reactive methoxyacetyl ester, which in turn can be selectively cleaved with methanol/tert-butylamine, while the ester group at the sn-1-position remains unaffected. The sequence has been shown to be suitable for preparation of spectroscopically labeled lysophosphatidylcholines. One of these compounds was readily converted to a double-labeled mixed-chain phosphatidylcholine applicable for real-time fluorescence resonance energy transfer (FRET) assay of lipolytic enzymes. In addition, the work led to new synthetic strategies based on chemoselective manipulation of the tosyl group in the presence of other base-labile groups such as FMOC derivatives that are often used for the protection of amino and hydroxyl groups in syntheses.
authors.affiliation: Department of Chemistry and Biochemistry, California State University-Northridge, Northridge, CA 91330-8262, USA.
authors.forename: Renato
authors.initials: R
authors.lastname: Rosseto
authors.forename: Niloufar
authors.initials: N
authors.lastname: Bibak
authors.forename: Rosemarie
authors.initials: R
authors.lastname: DeOcampo
authors.forename: Trishul
authors.initials: T
authors.lastname: Shah
authors.forename: Ara
authors.initials: A
authors.lastname: Gabrielian
authors.forename: Joseph
authors.initials: J
authors.lastname: Hajdu
mesh_terms: D001557:Benzenesulfonates / Q000138:chemical synthesis*; D005227:Fatty Acids / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D017665:Hydroxyl Radical / Q000737:chemistry; D007202:Indicators and Reagents; D008244:Lysophosphatidylcholines / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010743:Phospholipids; D010766:Phosphorylation; D013237:Stereoisomerism
chemical_list: D001557:Benzenesulfonates; D005227:Fatty Acids; D007202:Indicators and Reagents; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D017665:Hydroxyl Radical; C029501:4-toluenesulfonic acid