Amide ligation

The second methodology involves direct introduction of glycosylated moieties onto a suitably functionalized meso-arylporphyrin scaffold, accessible from a natural source (protoporphyrin-IX) or by total synthesis. Several O-,133,145,146 S-,147 and N-glycoporphyrins148 (125-129) have thus been prepared (Fig. 12). Moreover, in order to explore the influence of the clustered peripheral saccharides around the porphyrin scaffolds, and to evaluate their photophysical properties, the synthesis of dodecavalent porphyrins bearing four trivalent glycodendrons via amide ligation (129) has been achieved.149... 

Figure 20 CDA epoxidation by tailoring enzymes HxcO/HcmO. (a) CDA. (b) Proposed mechanism of HxcO/HcmO epoxidation to form trans-2,3-epoxyhexanoyl moiety, reaction intermediates, and products were characterized by online LC-FTMS and PEA. The stereochemistry of HxcO/HcmO reaction products was characterized by the amide ligation assay.52 (c) HxcO and HcmO substrate tolerance characterized By LC-IT-MS.

Schnolzer and Kent, 1992), oxime-fonning ligation (Rose, 1994) and thiol capture method (Liu and Tam, 1994) and activated amide ligation (Saxon et al, 2000). 

Marinzi C, Bark SJ, Offer J, Dawson PE (2001) A new scaffold for amide ligation. Bioorg Med Chem 9 2323-2328... 

It is important to cite several other recently developed methods for peptide ligation, which include the traceless Staudinger ligations of Bertozzi [62], Raines [63], and their co-workers, the decarboxylative amide ligation (KAHA ligation) developed by Bode et al. [64], and the Ser/Thr ligation of Li et al. [65, 66]. While these methods can be considered complementary to NCL, they have various constraints which limit their general utility. 

Bode et al. devised a unique chemoselective amide ligation by the decarboxylative condensations of a-ketoacids and A -alkylhydroxylamines (KAHA ligation) (Scheme 12) [64, 150-154]. This process requires neither coupling reagents nor catalysts, produces only water and carbon dioxide as by-products, and tolerates unprotected amino acid functional groups. It is also completely orthogonal to NCL and theoretically can be utilized at any junction. However, the limited access to A-alkylhydroxylamines and a-ketoacids restricts broader application of this chemistry. 

Table 2 Cyclic peptides prepared by a-ketoacid-hydroxylamine amide-ligation...

Kemp DS, Buckler DR (1991) Highly enantioselective amide ligation by prior thiol capture. Tetrahedron Lett 32 3013-3016... 

Fukuzumi T, Ju L, Bode JW (2012) Chemoselective cyclization of unprotected linear peptides by a-ketoacid-hydroxylamine amide-ligation. Org Biomol Chem 10 5837-5844... 

Figure 1, Concepts in orthogonai ligation to form a non-amide linkage between a pair of mutually reactive functional groups, a nucleophile and an electrophile, in the reaction centre (A), and amide ligation with a nucleophile and an electrophile in addition to a-acyl and a-amine moieties (B).

Studt F, Lehnert N, WieslerBE, Scherer A, Beckhaus R, Tuczek F. Spectroscopic comparison of dinuclear Ti and Ti p-r r dinitrogen complexes with Cp /pentafiilvene and amine/amide ligation moderate versus strong activation of N2. Eur J Inorg Chem. 2006 291-297. 

Bode JW, Fox RM, Baucom KD (2006) Chemoselective amide ligations by decarboxylative condensations of A-alkylhydroxylamines and n/p/tn-ketoacids. Angew Chem Int Ed 45 1248-1252... 

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