Other N-Linked Substituents

Other N-linked substituents. A-Nitropyridiniums are mild nitrating agents. 

The chemistry of the N-linked substituents of the 7r-deficient heterocycles principally concerns the reactivity of amino and nitro functions. The many other nitrogen functions are usually derived from either or both the amino or nitro parents and so are discussed within the two main Sections (2.06.4.1 and 2.06.4.2) below, as appropriate. 

There are three common approaches to the displacement of amine substituents from purines. First, diazotization and dediazoniation have been used to replace amine substituents, primarily with hydrogen or hydroxyl, carboxyl, and halide functionalities. Second, the S Ar reactions of quaternary ammonium substituents have provided useful synthetic adjuncts to the displacement reactions of halopurines. Finally, of increasing importance has been the conversion of aminopurines (or oxopurines) to N-linked 1,2,4-triazoles (and other azoles), which function as pseudohalogens and can be displaced by nucleophiles or take part in transition metal-catalyzed reactions. 

Biochemical analyses of the assembly of the ergopeptines in C. purpurea have shown that ergopeptines are the products of an enzyme complex consisting of two nonribosomal peptide synthetase (NRPS) subunits (55). NRPSs generally exhibit modular structures, with each module responsible for the addition of an amino acid or other substituent. A typical module includes an adenylation (A-) domain, a thiolation (T-) domain (also known as a peptidyl carrier protein domain), and a condensation (C-) domain. The A-domain specifies the amino acid or other carboxylic acid substituent, and activates by it by an ATP-dependent adenylation reaction. The activated substituent then forms a thioester with the 4 -phosphopan-tetheine prosthetic group in the adjacent T-domain. Finally, the C-domain links the substituent to the next substituent in the chain. In a multimodular NRPS protein, the order in which substituents are added corresponds to the arrangement of modules from its N- to C terminus. 

Despite the planar conformation of nitrogens, several possibilities are available for the introduction of chirality. It is possible to prepare benzim-idazolylidenes, triazolylidenes, imidazolylidenes or unsubstituted-backbone imidazolinylidenes with a stereogenic center on one or two N-substituents (carbenes I and II). The other possibility is to relay the imidazolinylidenes backbone stereogenecity via the N-substituents or to combine stereogenic N-substituents with a chiral backbone (carbenes III or IV). It is at least possible to prepare bis-carbenes of type V with one (or two) stereogenic link between the two carbenes (Fig. 7). 

Computations performed on an N-methylated imidazole showed that the presence of the methyl group increases the proton affinity of the other nitrogen. In contrast, a peptide substituent at a carbon adjacent to the nitrogen decreases its proton affinity. This can be explained by the conjugation stabilization of the peptide-substituted neutral form, which is absent in the protonated form. This result seems to indicate that heteroatomic rings linked by... 

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