Phosphorylation, chemoselective

CPL spectroscopy may also be used to signal the nature of the ternary anion adduct. In the series of phospho-anion complexes of [Eu.la]3+, Figure 5, complexes of HP042 and glucose-6-phosphate give identical CPL spectra - consistent with their very similar NMR spectral profile. Adducts with phospho-tyrosine, N-acetyl phospho-Tyr and a short peptide (phosphorylated at the Pyr residue) are also near-identical, consistent with chemoselective binding of the Tyr-OP phospho-anion. 

The introduction, removal and modification of substituents on the azetidinone nucleus has received some attention in addition to that mentioned earlier. Chemoselective phosphorylation of the 3-acylamino-azetidinone anion (29) has been achieved with alkyl phosphorodichloridate at low temperature. The diesters (30) were... 

SCHEME 4.215 Chemoselective phosphorylation of mixed halide species [354]. 

A new synthetic route has been developed for the synthesis of site-specifically phospholysine (pLys)-containing peptides. The strategy involved the chemoselective Staudinger-phosphite reaction between unprotected s-azido lysine-containing peptides (61) with phosphite esters (62) to afford the corresponding phosphoramidates (63) (Scheme 17). The site-specific localisation of phosphorylated lysine has been also demonstrated using electron-transfer dissociation (ETD) tandem mass spectrometry. 

C-terminal peptide tiiioesters are used extensively in synthetic protein chemistry, especially for native chemical ligation (NCL) and other chemoselective reactions, which has inspired a search for robust synthetic strategies. Initially, peptide thioesters were mainly prepared using solid-phase peptide synthesis with amino acids N -protected with Boc (Boc-SPPS) [1-3], see Chapter 4. However, this technique requires specialized equipment for handling of hydrofluoric acid (HP) for release of the peptide from the resin, and it is therefore currently not used in many laboratories. Furthermore, the HP treatment is incompatible with many post-translational modiflcations such as glycosylations or phosphorylations [4]. Boc-SPPS is described thoroughly in Chapter 4. 

Phosphorylation. Diethyl phosphorochloridate is highly electrophilic and can be cleanly reacted at an anionic center provided that prior metalation is regio- and chemoselective. For example, phenols, thiophenols, and anilines can be phosphorylated under basic conditions (eq 1). The phosphorylated compound can be isolated, or treated further with bases, resulting in orthomet-alation followed by a facile 1,3-phosphorus migration from the heteroatom to carbon. If carbon phosphorylation is desired, simply treating thiophenol with 2 equiv of n-Butyllithium followed by diethyl phosphorochloridate gave a moderate yield (58%). ... 

A selective protection and deprotection of o/t/jo-functionalised aryl-phosphonates (447) have been reported by Marchand-Btynaert and co-workers. The key step of the developed synthesis consisted of the introduction of a phosphoryl group by an o/t/jo-metallation reaction from protected ort/zo-anisidine. Chemoselective deprotections have been investigated and mono-, bis-, and ter-deprotected aromatic derivatives have been obtained. A practical route to phosphorylated benzoxazoles (448) has been thus discovered (Scheme 154). ... 

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