Activated azolides

In the reaction with steroidal dialcohols, activated azolides attack the less hindered OH-group with a high degree of preference [136]... 

Like N-activated esters, N-activated azolides can be used in azapeptide synthesis. These include imidazolides[30 33] and 1,2,4-triazolidesJ34 These intermediates 14 can be synthesized by addition of the corresponding heterocycle 10 to a-isocyanato carboxylates Ilf30 31 or from the amino component 12 and l,T-carbonyldiimidazole (13).[32 33]... 

Based on these reactivity studies on azolides, the imidazolides do not represent the most reactive members of the azolide family. In most cases, however, they are sufficiently reactive to undergo nucleophilic reactions leading to the desired products. Due to the easy and economical availability of imidazole, imidazolides are by far the most commonly used azolides for synthetic purposes. If, on the other hand, imidazolides are not sufficiently reactive in a specific case, one of the more active reagents from the arsenal of azolides might be used, as, for example, an azolide derived from a triazole or a tetrazole. 

The preparation of imidazolides by acylation of imidazole with acid chlorides is sometimes limited by the inaccessibility or instability of the required acid chlorides (e.g., formyl chloride, highly unsaturated acid chlorides, etc.) or by side-reactions in the case of multifunctional systems. For these reasons and due to the availability of an easy and convenient procedure involving very mild conditions, imidazolides today are usually prepared directly from the corresponding carboxylic acids with jV -carbonyldiimida-zole (CDI) or one of its analoga (see page 16). Use of these reagents has become more and more the preferred method for activation of carboxylic acids to azolides and their further transacylation to esters, amides, peptides, etc. (see subsequent Chapters). 

Preparation of a thiolester from an azolide activated by benzylation.[1413... 

Chemical modifications of proteins (enzymes) by reacting them with iV-acylimidazoles are a way of studying active sites. By this means the amino acid residues (e.g., tyrosine, lysine, histidine) essential for catalytic activity are established on the basis of acylation with the azolides and deacylation with other appropriate reagents (e.g., hydroxylamine). 

The azolide method has been used successfully in the conversion of an optically active aldehyde into the corresponding nitrile, with an optical purity of 100% [6]... 

Azolides used as inhibitors for monoamine oxidase1171 or human leucocyte elastase,1181 as inductors of recessive lethal genes in Drosophila,1191 as histamine H2-receptor antagonists,1201 as anti-ulcer agents,1211 or as pharmacophores for anthelmintic, analgesic, and antimicrobial activity 1221... 

Azolides used as activators for sodium percarbonate/perborate in laundry bleaching,1261-1291 for decreasing the affinity of polyamide textile materials for acid dyes,1301 and as antiflammatory agents 1311... 

Example 2 it has been assumed that selectivity should be observed when one of diastereomeric products from the azolide intermediate 3 (Scheme 1) is preferentially formed [16]. Engels and Shell demonstrated that in the case of methylphosphonates this goal can be achieved by the use of a specially synthesized activator 4,5-dicyanoimidazole [17]. Due to the fast epimeriza-tion, the starting phosphonoamidite can be used without separation into the individual diastereomers. 

The isocyanate reaction pathway seems to have no major advantage over the other methods with N-activation (vide supra), since it implies an additional reaction step and the isocyanates react directly with hydrazides giving azapeptides. Advantages may be the easier handling of the solid and stable TV-azolides in comparison to the liquid, toxic, and relatively unstable isocyanates. 

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