Desymmetrization of myo-inositol derivatives by lanthanide catalyzed phosphitylation with C2-symmetric phosphites. Issue 12 (15th June 2015)

• Record Type: Journal Article
• Authors: Duss, Michael; Capolicchio, Samanta; Linden, Anthony; Ahmed, Nisar; Jessen, Henning J.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 12(2015)
• Page Start: 2854
• Page End: 2861
• Publication Date: 2015-06-15
• Subjects: Inositol -- Phosphorylation -- Diphosphoinositol polyphosphates -- Chiral auxiliary -- Phosphite; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.03.023
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Desymmetrization by phosphorylation represents a promising method with potential impact in many different areas of research. C 2 -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 C 2 -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.