Desulfitative catalysis

Of the native carbon-heteroatom bonds that are biologically relevant (C-O, C-N, C-S), the C-S bond is particularly polarizable, and it therefore has the potential to engage in highly selective transformations catalyzed by thiophilic metals in the presence of C-O- and C-N-based functional groups. As a consequence, given its inherent chemoselectivity, the desulfitative catalysis could also play an important role in highly selective bioconjugative reactions where a biomolecule is coupled to another biomolecule, to a probe or therapeutic molecule, or to a nanomaterial (dot, tube, particle, etc.) or surface [7]. 

Figure 234 Generalization of Pd-catalyzed, Cu-mediated desulfitative catalysis.

Scheme 23.8 Cu-catalyzed desulfitative catalysis using metallothionein mimics.

Figure 23.6 Mechanisms of (a) the aerobic and (b) the anaerobic desulfitative catalysis. Water-solubilizing sites are in gray.

Scheme 23.10 Proteo-ketones via bioconjugative desulfitative catalysis.

The next phase of development of desulfitative catalysis will focus on its use in the synthetic manipulation of proteins and complex peptides (Scheme 23.10). To achieve this goal, the following hurdles must be overcome (i) the anaerobic catalysis using MT mimics must be modified for effective catalysis at room temperature and (ii) both the aerobic 5-acylthiosalicylamide substrates and the anaerobic MT mimic substrates must be modified for effective reaction in water at room temperature. 

Figure 23.7 Potential water-soluble substrates for desulfitative catalysis.

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