Hindered residues

In order to explain why in 33 the bond from zirconium to C-l is selectively cleaved rather than the zirconium-C-4 bond it is necessary to take note that this reaction involves allylic and homoallylic ethers and alkoxides. With such species the magnesium cation also coordinates with an oxygen atom from the substrate, as in model system 36. It can further be shown that in the transition from 33 to 34 zirconium generally remains with the statically least hindered residue even if there is no heteroatom present12... 

With respect to the influence on reactivity of the nature of the substituents and the interacting residues, Z and Boc amino acid derivatives exhibit similar reactivities,esters of hindered residues valine and isoleucine are much less reactive than those of other residues, and ferf-butyl esters are significantly better nucleophiles than ethyl esters. 

This mild procedure for the solid-phase synthesis of peptides containing sterically hindered residues can be easily extended to generate combinatorial libraries of unnatural peptides, which may display biological properties superior to those of natural counterparts. 

Smith G.G., Sol B.S. (1980) Racemization of amino acids in dipeptides shows COOH > NH2 for nonsterically hindered residues. Science 207, 765-7. 

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