Protection of amides

S Akabori, S Sakakibara, Y Shimonishi. Protection of amide nitrogen for peptide synthesis. A novel synthesis of peptides containing C-terminal glutamine, (xanthenyl) Bull Chem Soc Jpn 34, 739, 1961. 

In a recent NMR study, Derenne et al.(77) obtained evidence for non hydrolyzable amide structures in refractory fractions of the algae Scenedesmus quadricauda. The solid-state NMR spectra showed a major peak around -260 ppm for amides accompanied by a peak around -195 ppm for substituted pyrroles and a shoulder at -235 ppm assigned to unsubstituted pyrroles of the insoluble residue. The authors suggest, that the amides are protected by association with long polymethylenic chains within a macromolecular network. Knicker and Hatcher offer an alternative explanation,- that protection of amide functional groups as part of proteinaceous material are affected by encapsulation within the macromolecular matrix forming sedimentaryhumic material(7.. ... 

Protection of amidic nitrogen with di-tert-butyl dicarbonate (B0C2O), in acetonitrile at room temperature, as part of an efficient and regioselective method for the N-debenzoylation of Paclitaxd [Taxol ) 777 to 10-acetyldocetaxel and to Docetaxd 778, has been reported [566], Paclitaxd , and its semisynthetic analogue Doce-taxel (Taxotere ), are among the most important new antitumor agents of last decade. 

Amines can be activated for alkylation by N-formylation. Subsequent defoimylation of the alkylated formamide 11 has been a challenge. Longqin Hu of Rutgers University has developed (Tetrahedron Lett. 2007, 48, 4585) microwave conditions that work well. Carbamates are stable, but esters are not. Protection of amides can also be important. Michael J. Zacuto of Merck Process in Rahway, NJ has optimized (J. Org. Chem. 2007, 72, 6298) the Rh-catalyzed deaUylation of 13 to give 14. 

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