Peptides synthesis, metal-catalyzed

The development of chiral peptide-based metal catalysts has also been studied. The group of Gilbertson has synthesized several phosphine-modified amino adds and incorporated two of them into short peptide sequences.[45J,71 They demonstrated the formation of several metal complexes, in particular Rh complexes, and reported their structure as well as their ability to catalyze enantioselectively certain hydrogenation reactions.[481 While the enantioselectivities observed are modest so far, optimization through combinatorial synthesis will probably lead to useful catalysts. The synthesis of the sulfide protected form of both Fmoc- and Boc-dicyclohexylphosphinoserine 49 and -diphenylphosphinoserine 50 has been reported, in addition to diphenylphosphino-L-proline 51 (Scheme 14).[49 To show their compatibility with solid-phase peptide synthesis, they were incorporated into hydrophobic peptides, such as dodecapeptide 53, using the standard Fmoc protocol (Scheme 15).[451 For better results, the phosphine-modified amino acid 50 was coupled as a Fmoc-protected dipeptide 56, rather than the usual Fmoc derivative 52.[471 As an illustrative example, the synthesis of diphe-nylphosphinoserine 52 is depicted in Scheme 16J45 ... 

An alternative approach to metal-catalyzed peptide synthesis was proposed by Beck and co-workers. Their method uses half-sandwich complexes of Rh, Ir, or In this reaction, TV,TV -coordinated peptides are elongated at the... 

The application of transition metal-mediated reactions on solid support is an area of supreme interest for both peptide chemistry and the synthesis of nonpeptidic drug-like molecules. Although many metal-catalyzed reactions have been carried out on resin-bound scaffolds, there are scarce examples of metal-mediated solid-phase reactions promoted by a complexing agent that is covalently bound with the resin in close proximity of the scaffold. Dai and Sun have recently proposed an ingenious route toward the microwave-assisted solid-phase synthesis of a small library of 2-(hetero)aryl indoles. The authors demonstrated the strategic use of a tailor-made linker that features the dual function of a normal linker for scaffold attachment as well as of a promoter for the Cu(II)-mediated hetero-annulation of the intermediates (Scheme 8.17). 

Proteases of the trypsin family have recently been applied in the synthesis of peptides that self-assemble to nanofibrous structures and for preparing biomaterials. An example is the chymotrypsin-catalyzed polymerization of the amphiphilic peptide Lys-Leu-OEt to an alternating oligomer that forms a hydrogel [8]. Furthermore, ch3unotrypsin was used for the synthesis of poly-L-cysteine, a material for the selective chelation of SH-reactive metal ions. A high yield (80%) was obtained under mild reaction conditions [54]. 

One of the standard methods for preparing enantiomerically pure compounds is the enantioselective hydrogenation of olefins, a,/3-unsaturated amino acids (esters, amides), a,/3-unsaturated carboxylic acid esters, enol esters, enamides, /3- and y-keto esters etc. catalyzed by chiral cationic rhodium, ruthenium and iridium complexes ". In isotope chemistry, it has only been exploited for the synthesis of e.p. natural and nonnatural H-, C-, C-, and F-labeled a-amino acids and small peptides from TV-protected a-(acylamino)acrylates or cinnamates and unsaturated peptides, respectively (Figure 11.9). This methodology has seen only hmited use, perhaps because of perceived radiation safety issues with the use of hydrogenation procedures on radioactive substrates. Also, versatile alternatives are available, including enantioselective metal hydride/tritide reductions, chiral auxiliary-controlled and biochemical procedures (see this chapter. Sections 11.2.2 and 11.3 and Chapter 12). 

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