Neighboring Amides

Polyfunctional 2-hydtoxyalk5iamides can serve as cross-linkers for carboxyHc acid-terrninated polyester or acryHc resins (65). The hydroxyl group is activated by the neighboring amide linkage (66). SoHd grades of hydroxyamides are finding use as cross-linkers for powder coatings (67). 

This observation led Dado and Gellman [63] to postulate that (i) such H-bonds between nearest neighbor amide groups, should they occur, would compete with... 

It is well documented that the isoimide is the kinetically favoured product and that isomerization yields the thermodynamically stable imide when sodium acetate is used as the catalyst. High catalyst concentrations provide maleimides with low isoimide impurity. The mechanism by which the chemical imidization is thought to occur is shown in Fig. 3. The first step in the dehydration reaction may be formation of the acetic acid-maleamic acid mixed anhydride. This species could lose acetic acid in one of the two ways. Path A involves participation by the neighboring amide carbonyl oxygen to eject acetate ion with simultaneous or subsequent loss of proton on nitrogen to form the isoimide. Path B involves loss of acetate ion assisted by the attack of nitrogen with simultaneous or subsequent loss of the proton on nitrogen to form the imide. If the cyclodehydration is run in acetic anhydride in the absence of the base catalyst, isoimide is the main reaction product. 

Our next optimization step consisted in introduction of substituents in the 4-position of the aromatic peptide subunits of 3 [18]. These substituents should affect the rotation of neighboring amide groups by steric effects. More importantly, if they can form hydrogen bonds to the amide protons they should stabilize peptide conformations in which all NH groups point away from the cavity center. This effect would not only affect the flexibility but also the anion-binding ability of 3, because, for the latter, a conformation with converging NH groups is required. To... 

N-Phthalimide-linked peptides that contain C-terminal a-amidotrimethylsilyl groups undergo macrocyclization reactions via sequential single-electron transfer processes [11, 12]. Thus, electron transfer from the neighboring amide to the excited phthalimide chromophore leads to an amide radical cation. Hole migration to the ot-amidotrimethylsilane center is followed by desilylation to form an 1, co-biradical intermediate, which finally cydizes to the macrocydic peptide (Scheme 9.9). 

Complications in this procedure when applied to proteins might arise from the reaction of imidazole units with FDNB (cf. Gundlach et al., 1959a, b) or from the possibility of intramolecular assistance from a neighboring amide (imidole) group in the process of elimination, as is pictured for glutathione (XXXI) (Calvin, 1954). Such a reaction could lead to an oxazoline (XXXII). 

Rearrangement. A cyclopropyl group is liable to expand during reduction of a neighboring amidic carbonyl. 

One approach is a combination of the above-mentioned 6D APSY-seq-HNCOCANH with the 5D APSY-HNCOCACB experiment [63]. Thereby, the 6D APSY scheme [50] coimects neighboring amide groups sequentially, and the 5D APSY scheme measures the chemical shifts. These two experiments can also be combined into a single magnetization transfer pathway, the 7D APSY-seq-HNCO(CA)CBCANH (Figs. 7a, and 8) [63]. Magnetization of the amide proton i is transferred with seven subsequent INEPT [64] steps to the amide proton / 1 (steps a-g in Fig. 7a). Along this pathway, six evolution periods are... 

The decomposition of suitably crafted diazoimides 181, in the presence of a transition metal catalyst, affords the metallo-carbenoids 182 that undergo intramolecular cycUzation onto the neighboring amide carbonyl oxygen to form the five-membered ring carbonyl yUdes (isomiinchnones) 183 (Scheme 58). Early examples of inter- and intramolecular 1,3-dipolar cycloaddition of the mesoionic ylides 183 have mainly emanated from the research groups of Ibata [149], Maier [150] and Padwa [151]. These reactive species (isomimchnones) can be trapped by various electron-rich and electron-deficient dipolarophiles [152] to furnish the cycloadducts in high yield. Much work has been reported in this area and for clarity of presentation is described here under various subheadings. 

The other typical example is a SAM formed of alkanethiols with an amide bond in the interior of a single alkane chain (Fig. 8) [256, 257]. Such a SAM has stability based on the lateral interaction not only due to van der Waals chain-chain interaction but also due to hydrogenbonding interaction between neighboring amide moieties. A SAM formed from a mixed solution of this amidelong-chain alkanethiol with a commonly used alkanethiol results in the phase separation [258]. 

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