Side-chain carboxy acids, Synthesis

Synthesis of Side-chain Carboxy Acids.—The side-chain carhoxy acids being really aryl substituted aliphatic acids are synthesized by methods characteristic of such acids. 

By Grignard Reaction.—Exactly analogous to the Grignard synthesis of ring carboxy acids is the synthesis of side-chain carboxy acids by the introduction of carbon dioxide into the Grignard reagent. 

Solid-phase peptide synthesis is based on the sequential addition of protected amino acids onto an insoluble support. Addition proceeds from carboxy terminus to amino terminus. The first amino acid is attached to a solid support by a linker and, if necessary, side-chain amino acid function is protected throughout chain assembly. The carboxy group of the in-coming, acylating amino acid is activated for coupling while its amino group is protected temporarily for each coupling step and then deprotected for the next cycle. The... 

The next residues were attached successively by dicyclohexylcarbodiimide-mediated coupling of Boc-amino acids with the free amino groups. The use of excess Boc-amino acid eliminated the need for capping after coupling. The last Boc-group and the benzyl-based side chain and carboxy-terminal protectors were removed at the end of the synthesis by acidolysis with hydrogen bromide in trifluoroacetic acid the latter was used instead of acetic acid to avoid acetylation of hydroxymethyl side chains (see Section 6.6). Catalytic hydrogenolysis of the peptide removed the nitro... 

N -Protection as allyl carbamate is used generally only for specific synthetic purposes where acid- or base-mediated deprotection procedures must be avoided or reduced to a minimal extent as in the case in the synthesis of glyco- and phosphopeptides (see Sections 6.3 and 6.5). Otherwise the orthogonality of this type of amino protection has been mainly exploited in side-chain protection to allow for selective chemistry such as selective acylations, e.g. cyclizations, to be performed on protected peptides in solution or in the resin-bound state (see Section 4.3.2.3.4). An additional interesting application of the Aloe group is the one-pot deprotection and acylation with carboxy components resistant to the paUadium(0)-catalyzed allyl cleavage by hydrostannolysis as reported in Section 4.3.2.3.4.P 1... 

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 ... 

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