Synthesis of Unsymmetric Diphospho‐Inositol Polyphosphates

Abstract

One to rule them all: A novel C2‐symmetric phosphoramidite was developed that can be used to prepare all four unsymmetric diphospho inositol pentaphosphates (PP‐InsP5). The target structures were synthesized in few steps and high enantiomeric ratios. With the obtained compounds, specificity of Ddp1 from yeast (a PP‐InsP5 phosphatase) was studied.

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…Intermediates such as 171 can also be generated from the elimination of other protecting groups followed by TMS masking in a similar manner. (175) and (176) The meso-silylated orthoester 179 was prepared in two steps from myo-inositol [225] allowing the 4-and 6-hydroxyl groups to be mono-phosphorylated (using the phosphitylating reagent 164) that are then oxidised to the chiral mono-phosphates at the 4-and 6-position, 180 and 181 respectively. The two diastereoisomers were then separated by chromatography and identified using X-ray diffraction.…”

myo-Inositol 1,3-acetals as early intermediates during the synthesis of cyclitol derivatives

“…[1][2][3][4][5] Realization of the fact that the production and destruction of pyrophosphates of inositol are highly regulated by enzymes in living cells (bacteria to mammals) has recently augmented the interest in the synthesis of phosphorylated inositol derivatives and their analogs. [6][7][8] Phosphatidylinositol (2) is a component of mammalian cell membranes. Phosphorylated derivatives of 2 play a fundamental role in a multitude of cellular processes.…”

Prometabolites of 5‐Diphospho‐myo‐inositol Pentakisphosphate

“…[10] Theu se of orthogonal protecting groups facilitated the generation of bioreversibly protected P-anhydrides in ao nepot process.T his method has been developed for the generation of benzyl-protected X-PP-InsP 5 [7,11] and 1/3,5-(PP) 2 -InsP 4 [12] and has additionally been applied in the synthesis of 5-PP-InsP 4 . [13] Notably,t he application of this method leaves the a-phosphate unprotected:T he negative charge on this phosphate is required to obtain an inert, terminally protected P-anhydride that does not rapidly hydrolyze under aqueous conditions.M odification of the method allowed the introduction of both (AB) 2 and (SATE) 2 phosphates and the generation of aterminally monoprotected AB analogue as in 3.This was achieved by the development of nonsymmetric P-amidite 10 containing both an AB and af luorenylmethyl group,w hich can be removed selectively.…”

“…Thed egradation profile and the cellular uptake were furthermore analyzed by polyacrylamide gel electrophoresis (PAGE) in combination with TiO 2 based inositol phosphate extraction and mass spectrometry. [6] Thes ynthesis commenced with previously reported benzylidene acetal 6, [7] which was phosphorylated with b-cyanoethyl P-amidite 7 in the 5-position (Scheme 1). After cleavage of the benzylidene acetal and the para-methoxybenzyl groups,phosphate triester 11 was phosphitylated with P-amidites 8…”