Protection of carboxy groups

As will be seen later, peptide-bond formation can be achieved by converting the intended TV-protected TV-terminal residue into a reactive derivative of the carboxy function in the absence of the C-terminal moiety to which it is to be coupled. In these circumstances, it is not always necessary to protect the carboxy group of the latter. The C-terminal moiety then has both the a-amino group and the terminal 

Benzyl esters and substituted benzyl esters are also easily prepared but possess the advantage that deprotection can be achieved without using alkali. Benzyl esters are 

Protection of e-amino groups in proteins by means of the trifluoroacetyl group was introduced many years ago in order to limit the action of trypsin to the cleav- 

---

Allyl (Al) esters are suitable for the temporary protection of carboxy groups in peptide and glycopeptide synthesisP " and also in the synthesis of cyclic peptides.In the latter case these esters allow, for example, on-resin head-to-taU cyclizations of peptides that are attached via the side chains of aspartic acid and glutannic acid residues to the solid support.t 1 The application of aUylic protecting groups in peptide synthesis has been comprehensively reviewed by Guibe.f ... 

The cyclopentyl (cPe) ester group was introduced by Blake for the protection of carboxy groups. The ester bond is stable against TFA and readily cleaved with HF at 0 °C. This ester is 14 times more stable than the corresponding benzyl ester when exposed to 55% TFA in dichloromethane. However, there is little difference in the extent of HF-catalyzed succini-mide formation between peptidyl-resins containing benzyl- or cyclopentyl-protected aspartyl residues, although the latter protection reduces base-catalyzed succinimide formation. 

Protection and Deprotection.— The formation of esters of 2-hydroxymethyl-anthraquinone has been shown to be a useful method for the protection of carboxy-groups of a-amino-acids. Such derivatives, designated Maq esters, are stable to TEA, HCl, and triethylamine, and can be hydrolysed in quantitative yield by a number of methods. They offer, moreover, the advantages of high crystallinity and... 

MgBr2 removal of SEM groups is also useful for deprotection of carboxy groups in N-protected amino acids. 

Protection of hydroxy groups is commonly effected by forming the t-butyl ether by reaction with isobutene in the presence of sulphuric or toluene-ju-sulphonic acid, just like with carboxy groups (Section 7.4). Consequently, both groups may be blocked simultaneously by starting with the free acid. t-Butyl ethers are readily cleaved by trifluoroacetic acid. 

Hydrogen peroxide sulfuric acid Protection of sulfhydryl groups as carboxy methyl thio ethers... 

The cyclobutane ring was then cleaved by hydrolysis of the enamine and ring opening of the resulting (3-diketone. The relative configuration of the chiral centers is unaffected by subsequent transformations, so the overall sequence is stereoselective. Another key step in this synthesis is Step D, which corresponds to the transformation 10-IIa => 10-la in the retrosynthesis. A protected cyanohydrin was used as a nucleophilic acyl anion equivalent in this step. The final steps of the synthesis in Scheme 13.11 employed the C(2) carbonyl group to introduce the carboxy group and the C(l)-C(2) double bond. 

Because primary hydroxy groups are somewhat more reactive toward CDI than a carboxy group, the method was modified for chain elongations of co-hydroxycarboxylic acids with protection of the OH-group [41]... 

GHL Nefkens, B Zwanenburg. Boroxazolidones as simultaneous protection of the amino and carboxy group in a-amino acids. Tetrahedron 39, 2995, 1983. 

M Meldal, KJ Jense. Pentafluorophenyl esters for temporary protection of the a-carboxy group in solid phase glycopeptide synthesis. J Chem Soc Chem Commun 483, 1990. 

---