Protection heptyl esters

The heptyl ester was developed as an enzymatically removable protective group for C-terminal amino acid protection. 

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. 

The full capacity of the lipase-mediated technique for C-terminal deprotection is demonstrated in the synthesis of complex C>-glycopeptides, which are sensitive to both acids and bases, The key starting material, serine glycoside heptyl ester 11, is selectively depro-tected at the C-terminus by lipase obtained from the fungus Mucor javanicus (Scheme 22). The free carboxylic acid derivative 12 is coupled with an N-terminally protected glyco-dipeptide 13 to generate the tripeptide 14. 

The lipase from the fungus Rhizopus niveus accepts a variety of protected dipeptide heptyl esters (33) and hydrolyzes the ester function in high yields at pH 7 and 37 °C without damaging the urethane protecting groups and the peptide bonds. The N- and C-terminal amino acid can vary over a wide range, but, with increasing steric bulkiness and hydrophobicity of the amino acids, especially the C-terminal one, the reaction rates decrease. 

The target molecule 19 was obtained by lipase-catalyzed heptyl ester cleavage and employing sodium methanolate for the removal of the 0-acetyl groups. In summary, this result showed a set of three base-labile protecting groups (Fmoc, OAc, OHep) to be removable selectively and thus useful for the synthesis of complex glycopeptidic structures. 

PROP Extract of Acorns calamus L., (Fam. Araceae). Containing asarone, eugenol esters of acetic and heptylic acids. Volatile oil. Yellow to yellowish-brown liquid (viscid) aromatic odor, bitter taste. D 0.960-0.9707 20°/20°. Very sidy sol in water misc with ale. Keep well closed, cool, and protected from light. 

In these protease-catalyzed cleavages of the C-terminal protecting groups, it has to be taken into consideration that an undesired hydrolysis of peptide bonds can occur, especially if unnatural and poor substrates are subjected to enzyme-mediated transformations. The use of enzymes which cannot cleave amides at all enables this undesired side reaction to be overcome. This principle has been realized in the development of the heptyl (Hep) ester [13,14,48,49] as carboxyl protecting group, which can be enzymatically removed by means of lipases (Fig. 10). 

In the discussion of the protease-catalyzed cleavage of the N-terminal protecting groups it has already been pointed out that the use of biocatalysts belonging to this class of enzymes in general, i. e. also for the C-terminal deblocking, may lead to an undesired hydrolysis of peptide bonds. In particular, this has to be expected if the respective ester or amide to be hydrolyzed turns out to be only a poor substrate, which is only attacked slowly, an experience not uncommon if unnatural substrates are subjected to enzyme mediated transformations. This undesired possibility would, however, be overcome if enzymes were used which were not able to split amides at all. This principle has been realized in the development of the heptyl... 

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