Protecting groups carboxy

H. Kunz and H. Waldmann, The allyl group as mildly and selectively removable carboxy-protecting group for the synthesis of labile O glycopeptidcs, Angew. Chem. lnt. Ed. Engl. 23 71 (1984). 

Ring closure of (3-hydroxy-a-amino acids with sulfuryl chloride/triethylamine 68 is accompanied by formation of (3-chloroalanine,16 1 whereas cyclization of urethane-protected serine and threonine by the Mitsunobu reaction 54 69 70 leads to oxazoline and dehydroalanine formation as side products. 47,71 Formation of dehydroalanine can be prevented by bulky carboxy protecting groups such as tert-butyl esters. 69 ... 

R1 = H, N protecting group (e.g., Z, Boc, Fmoc, Tos, Bzl) R2 = amino acid side chain R3 = H, carboxy protecting group R4 = H, alkyl, functionalized alkyl L = leaving group... 

R2 = amino acid side chain R3 = H, carboxy protecting group R4 = alkyl, functionalized alkyl... 

Braun, P., Waldmann, H., and Kunz, H. (1992) Selective enzymatic removal of protecting functions heptyl esters as carboxy protecting groups in glycopeptide synthesis. Synlett 1, 39 10. 

In a formal sense, alkyl ester type carboxy protecting groups, e.g. benzyl, allyl, 4-picolyl, and (9,10-dioxo-2-anthryl)methyl esters, can be viewed at as modified methyl esters. However, because of their specific properties and cleavage conditions these esters will be discussed separately. In this section a series of acetal, phthalimidomethyl, various phenacyl, acetonyl, 9-anthryhnethyl, and cyclopropyhnethyl esters will be presented. 

A new carboxy protecting group that takes advantage of the facile solvolysis of cyclopropyl methyl substrates was proposed by Carpino et al.f The dicyclopropylmethyl (Dicyc-propme) ester can be used for carboxylic acid protection where selective removal is required in the presence of tBu or Trt side-chain protection. The ester is stable toward conditions of... 

Other carboxy protecting groups which have been reported but have not gained widespread use are summarized in Scheme 18. 

Any of the carboxy protecting groups discussed above are applicable to the side-chain protection of aspartic and glutamic acids. A procedure for the preparation of a di(4,5-dimethoxy-2-nitrobenzyl) aspartate was given in Section 2.4.2.I.2. Selective saponification with LiOH leads to the side-chain protected product.P l... 

The problem of undesired hydrolysis of peptide bonds occurring during deprotection can be avoided completely by choosing enzymes devoid of any protease activity. For example by using and 2-bromoethylt l esters as carboxy protecting groups for pep-... 

Table 1 lists the commonly used hydroxy protecting groups, together with their stability, selectivity to amino and carboxy protecting groups, and cleavage conditions. 

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