title: Desymmetrization of myo-inositol derivatives by lanthanide catalyzed phosphitylation with C2-symmetric phosphites.
abstract: Desymmetrization by phosphorylation represents a promising method with potential impact in many different areas of research. C2-Symmetric phosphoramidites have been used to desymmetrize myo-inositol derivatives by functionalization at different positions. With this method, 1:1 mixtures of diastereomers are obtained that can be separated subsequently. In this work, activation of a C2-symmetric phosphoramidite is achieved by addition of pentafluorophenol (PFP) and leads to a reactive PFP phosphite, which can then be coupled to protected myo-inositol derivatives with reactive OH groups at the 1, 3, 4 and 6 positions. This strategy enhances the diastereoselectivity of the coupling reaction with a preference towards phosphitylation at position 6 (up to 3:1) or position 3 (up to 2:1). The concept of attenuative activation of phosphoramidites via in situ generated pentafluorophenol phosphite triesters is thus proven in these studies. It is further shown that Lewis-Acid catalysis enhances the rate of phosphite triester coupling without affecting the diastereoselectivity. This novel strategy improves access to different phosphorylated myo-inositol derivatives and will thus enable further studies into the function of these important intracellular second messengers.
authors: University of Zürich, Department of Chemistry, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Michael
authors: M
authors: Duss
authors: University of Zürich, Department of Chemistry, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Samanta
authors: S
authors: Capolicchio
authors: University of Zürich, Department of Chemistry, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Anthony
authors: A
authors: Linden
authors: University of Zürich, Department of Chemistry, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Nisar
authors: N
authors: Ahmed
authors: University of Zürich, Department of Chemistry, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Electronic address: henningjacob.jessen@chem.uzh.ch.
authors: Henning J
authors: HJ
authors: Jessen
mesh_terms: D002384:Catalysis; D018360:Crystallography, X-Ray; D054879:Halogenation; D007294:Inositol / Q000031:analogs & derivatives*; D028581:Lanthanoid Series Elements / Q000737:chemistry; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry; D017905:Phosphites / Q000737:chemistry*; D010766:Phosphorylation; D013237:Stereoisomerism
chemical_list: D028581:Lanthanoid Series Elements; D009943:Organophosphorus Compounds; D010636:Phenols; D017905:Phosphites; C434331:phosphoramidite; D007294:Inositol
keywords: Chiral auxiliary; Diphosphoinositol polyphosphates; Inositol; Phosphite; Phosphorylation