Simple one-pot regioselective 6-O-phosphorylation of carbohydrates and trehalose desymmetrization

Joseph, A. Abragam; Chang, Cheng-Chun; Wang, Cheng‐Chung

doi:10.1039/c3cc47180b

Cited by 24 publications

(6 citation statements)

References 37 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Global phosphorylation procedures described in the literature were generally performed on proteins or on linear peptides bound to resin, bearing one or two function(s) to be phosphorylated . Chemical phosphorylation of alcohols can be achieved by using P V or P III reagents, followed by oxidation . Current protocols recommend to use a large excess of phosphoramidites (10 equiv/function) to phosphitylate alcohols before applying an oxidant (11 equiv/function)—usually hydroperoxide or iodine—to produce the final phosphorylated residues.…”

Section: Resultsmentioning

confidence: 99%

“…[19] Chemicalp hosphorylation of alcohols can be achieved by using P V or P III reagents, followed by oxidation. [20] Current protocols recommend to use al arge excess of phosphoramidites (10 equiv/function) to phosphitylate alcohols before applying an oxidant( 11 equiv/function)-usually hydroperoxide or iodine-top roduce the final phosphorylated residues.These reactions must be performed under an inert atmosphere because the reagents are sensitive to air and water. Consequently,t he synthesis of phosphate-rich cyclic peptides, containing ah igh density of phosphorylated residues (3 to 4 pSer over 10 amino acids) represents as ynthetic challenge, and all the steps must be performed in the solid phase.…”

Section: Synthesis Of Phosphate-richcyclodecapeptidesmentioning

confidence: 99%

See 1 more Smart Citation

Phosphate‐Rich Biomimetic Peptides Shed Light on High‐Affinity Hyperphosphorylated Uranyl Binding Sites in Phosphoproteins

Laporte

Lebrun

Vidaud

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

Some phosphoproteins such as osteopontin (OPN) have been identified as high‐affinity uranyl targets. However, the binding sites required for interaction with uranyl and therefore involved in its toxicity have not been identified in the whole protein. The biomimetic approach proposed here aimed to decipher the nature of these sites and should help to understand the role of the multiple phosphorylations in UO22+ binding. Two hyperphosphorylated cyclic peptides, pS168 and pS1368 containing up to four phosphoserine (pSer) residues over the ten amino acids present in the sequences, were synthesized with all reactions performed in the solid phase, including post‐phosphorylation. These β‐sheet‐structured peptides present four coordinating residues from four amino acid side chains pointing to the metal ion, either three pSer and one glutamate in pS168 or four pSer in pS1368. Significantly, increasing the number of pSer residues up to four in the cyclodecapeptide scaffolds produced molecules with an affinity constant for UO22+ that is as large as that reported for osteopontin at physiological pH. The phosphate‐rich pS1368 can thus be considered a relevant model of UO22+ coordination in this intrinsically disordered protein, which wraps around the metal ion to gather four phosphate groups in the UO22+ coordination sphere. These model hyperphosphorylated peptides are highly selective for UO22+ with respect to endogenous Ca2+, which makes them good starting structures for selective UO22+ complexation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Synthesis Of Phosphate-richcyclodecapeptidesmentioning

confidence: 99%

Phosphate‐Rich Biomimetic Peptides Shed Light on High‐Affinity Hyperphosphorylated Uranyl Binding Sites in Phosphoproteins

Laporte

Lebrun

Vidaud

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…A protocol for selective exchange of silyl for phosphoryl groups has been developed, enabling the synthesis of 6- O -phosphorylated carbohydrate derivatives from per- O -TMS-protected substrates (see sections and for related reactivity of per- O -silylated sugars) . This method was used to effect the 6′-O-phosphorylation of lactose, cellobiose, and fructose (e.g., 309 , Scheme ) and the desymmetrization of trehalose ( 310 , Scheme ).…”

Section: Reactions With Phosphorus-centered Electrophilesmentioning

confidence: 99%

Site-Selective Functionalization of Hydroxyl Groups in Carbohydrate Derivatives

2018

View full text Add to dashboard Cite

Methods for site-selective transformations of hydroxyl groups in carbohydrate derivatives are reviewed. The construction of oligosaccharides of defined connectivity hinges on such transformations, which are also needed for the preparation of modified or non-natural sugar derivatives, the installation of naturally occurring postglycosylation modifications, the selective labeling or conjugation of carbohydrate derivatives, and the preparation of therapeutic agents or research tools for glycobiology. The review begins with a discussion of intrinsic factors and processes that can influence selectivity in reactions of unprotected or partially protected carbohydrate derivatives, followed by a description of transformations that engage two OH groups in cyclic adducts (acetals, ketals, boronic esters, and related species). An overview of the various classes of site-selective transformations of OH groups in sugars is then provided: the reactions discussed include esterification, thiocarbonylation, alkylation, glycosylation, arylation, silylation, phosphorylation, sulfonylation, sulfation, and oxidation. Emphasis is placed on recently developed methods that employ reagent or catalyst control to achieve otherwise challenging transformations or site-selectivities.

show abstract

“…The target compounds are composed of three structural units, including a cholesteryl aglycon, a sugar core, and a phosphate ester at C6 with variable glycerol ester side chains. These structural units present several synthetic challenges, including: 1) regioselective phosphorylation of the C6‐hydroxy group,7 2) avoidance of phosphite acetal formation as seen in previous research,8 3) installment of the phosphatidyl group while avoiding acyl migration on the glycerol unit, and 4) regioselective oxidation of the phosphorus atom without oxidizing the double bond of cholesterol 9. We envisioned starting the synthetic route with per‐ O ‐TMS αCG ( 4 , Figure 3)10 because of its ready availability in two steps from glucose and its compatibility with the required criteria.…”

Section: Methodsmentioning

confidence: 97%

Synthesis and Structural Characterization of Three Unique Helicobacter pylori α‐Cholesteryl Phosphatidyl Glucosides

2014

View full text Add to dashboard Cite

Steryl glycosides produced by bacteria play important biological roles in the evasion and modulation of host immunity. Step‐economical syntheses of three cholesteryl‐6‐O‐phosphatidyl‐α‐D‐glucopyranosides (αCPG) unique to Helicobacter pylori have been achieved. The approach relies upon regioselective deprotection of per‐O‐trimethylsilyl‐α‐D‐cholesterylglucoside at C6 followed by phosphoramidite coupling. Global TMS ether deprotection in the presence of oxygen and subsequent deprotection of the cyano ethyl phosphoester afforded the target compounds in 16–21 % overall yield starting from D‐glucose. The structures of these natural products were determined using a combination of 2D NMR methods and mass spectrometry. These robust synthesis and characterization protocols provide analogues to facilitate glycolipidomic profiling and biological studies.

show abstract

Simple one-pot regioselective 6-O-phosphorylation of carbohydrates and trehalose desymmetrization

Abstract: Biologically essential carbohydrate 6-phosphates, especially trehalose 6-phosphate, can be synthesized easily in excellent overall yields in 2 steps involving minimum protecting group manipulations. We can cleave the diphenylphosphate group for further synthetic objectives.

Cited by 24 publications

References 37 publications

Phosphate‐Rich Biomimetic Peptides Shed Light on High‐Affinity Hyperphosphorylated Uranyl Binding Sites in Phosphoproteins

Phosphate‐Rich Biomimetic Peptides Shed Light on High‐Affinity Hyperphosphorylated Uranyl Binding Sites in Phosphoproteins

Site-Selective Functionalization of Hydroxyl Groups in Carbohydrate Derivatives

Synthesis and Structural Characterization of Three Unique Helicobacter pylori α‐Cholesteryl Phosphatidyl Glucosides

Contact Info

Product

Resources

About