Tandem ligation

To extend the scope of NCL, efforts have been made to introduce modifications so as not to depend on a Cys site. Cys residues can be selectively desulfurized to Ala [124], even in the presence of Cys(Acm) and Met [125]. Homocysteine and selenocysteine also serve as ligation sites, and can then be converted into Met [126] and into Ala or didehydroalanine, respectively [127]. Recently, ligation at Phe sites has also been accomplished [128]. The use of auxiliaries that are removed after ligation has been extensively studied [129-134]. NCL has also been applied to SPPS [135, 136], and to the synthesis of cyclic peptides [137-139], In another extension of the technique, proteins have been prepared by tandem ligation [135, 140], and expressed protein ligation [141]. Recently, NCL has been applied to the synthesis of glycoproteins [104, 142-144]. 

A consideration in a tandem strategy is the choice of two pairs of nucleophiles and electrophiles to achieve the reaction sequences of cyclization and convergent ligation. One entire pair essential for the cyclization reaction is placed in the peptide precursor, while the other pair for the convergent ligation is split between the peptide and the core. Although various combinations of these pairs can be exploited for the sequential reactions in thiol and... 

Fig. 10. Schematic view of the Inductively-Coupled Plasma (ICP) Selected-Ion Flow Tube (SIFT) tandem mass spectrometer. The ICP torch produces metal ions M+ that are mass-selected and injected into the flow tube. The M+ ions may be ligated with molecules L before they enter the reaction region further downstream...

Recently, metathesis of cyclooctane was reported using the tandem system having the pincer-ligated iridium complexes for hydrogenation/dehydrogenation and Schrock-type Mo-alkylidene complexes for olefin metathesis [78]. However,... 

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