Peptide-catalysed alcohol kinetic resolutions

Scheme 13.1 Kinetic resolution of racemic acetamido alcohols catalysed by peptides 1-3.

Miller and coworkers demonstrated a successful application of a peptide-catalysed kinetic resolution in the total synthesis of (-)-mitosane, which is a key intermediate for mitomycin C synthesis. A pentapeptide was found to effect kinetic resolution via acylation of a racemic alcohol with a A ei of 27. ° To expand the scope of applications of peptide catalysts to substrates lacking additional hydrogen-bond donors and acceptors, the group of Miller initiated a screening of a peptide library containing potential catalysts (resin bound. 

Scheme 13.3 Kinetic resolution of secondary alcohols catalysed by peptide 4.

In addition to kinetic resolution processes, the previously described peptide-catalysed acylation reaction of alcohols can be applied to desymmetrisation of meso compounds. In 2005, Miller and coworkers published the desymmetrisation of prochiral glycerol derivatives via enantioselective acylation of one primaiy alcohol function. A (3-tum histidine-based pentapeptide was identified as the most promising catalyst from a peptide libraiy and afforded the monoacylated product with up to 97% enantiomeric excess. One year later Miller and Hansen successfully demonstrated the desymmetrisation of a meso bis-phenol compound, which was found to be challenging because of the large distance between the two OH groups as well as between the desired site of functionalisation and the prochiral stereogenic centre of the substrate. The nucleophilic N-methylhistidine containing peptide 9 was identified as a powerful tool for monoacylation via extensive libraiy... 

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