Peptides unsaturated

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

Schemes are available, however, that start from the free carboxylic acid, plus an activator . Dicyclohexylcarbodiimide, DCC, has been extensively employed as a promoter in esterification reactions, and in protein chemistry for peptide bond formation [187]. Although the reagent is toxic, and a stoichiometric concentration or more is necessary, this procedure is very useful, especially when a new derivative is targeted. The reaction usually proceeds at room temperature, is not subject to steric hindrance, and the conditions are mild, so that several types of functional groups can be employed, including acid-sensitive unsaturated acyl groups. In combination with 4-pyrrolidinonepyridine, this reagent has been employed for the preparation of long-chain fatty esters of cellulose from carboxylic acids, as depicted in Fig. 5 [166,185,188] ...

Alternatively, rigidification of the y-peptide backbone to avoid H-bonds between nearest neighbors can be achieved by the introduction of an a,y9-unsaturation into the backbone of each y-amino acid constituent (vinylogous peptides) ]208, 209]. Recent ab-initio calculations suggested that the a,/9-unsaturated y-peptide backbone might support the formation of helices with large 19- and 22-membered H-bonded pseudocycles ]221]. 

While conformation II (Fig. 2.34) of Uke-y -amino acids is found in the 2.614-helical structure, conformation I, which similarly does not suffer from sy -pen-tane interaction, should be an appropriate alternative for the construction of sheet-like structures. However, sheet-like arrangement have not been reported so far for y-peptides composed of acyclic y " -amino acid residues. Nevertheless, other conformational biases (such as a,/9-unsaturation, cyclization between C(a) and C(y)) have been introduced into the y-amino acid backbone to restrict rotation around ethylene bonds and to promote extended conformation with formation of sheets in model peptides. Examples of such short chain y-peptides forming antiparallel (e.g. 152 [208]) and parallel (e.g. 153-155 [205, 208]) sheet-hke structures are shown in Fig. 2.38. 

Fig. 2.38 sheet forming y-peptides. (A) Crystal structure of the two stranded antiparallel sheet formed by a,j -unsaturated y-dipeptide 152 with a-methyl substituted residues [208], Both intermolecular H-bonds are characterized by a N---0 distance of 2.84 A and an angle (N-H- -O) ofl54.2°. (B) Crystal structure of the infinite parallel sheet arrangement formed by vinylogous dipeptide 153 [208], Intermolecular H-bonds are characterized by a N -O distance of 2.88 A and 3.24 A and an... 

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). 

Many enzymes have absolute specificity for a substrate and will not attack the molecules with common structural features. The enzyme aspartase, found in many plants and bacteria, is such an enzyme [57], It catalyzes the formation of L-aspartate by reversible addition of ammonia to the double bond of fumaric acid. Aspartase, however, does not take part in the addition of ammonia to any other unsaturated acid requiring specific optical and geometrical characteristics. At the other end of the spectrum are enzymes which do not have specificity for a given substrate and act on many molecules with similar structural characteristics. A good example is the enzyme chymotrypsin, which catalyzes hydrolysis of many different peptides or polypeptides as well as amides and esters. 

The first example describes the synthesis of a pyrimidine derivative. Starting from a, 3-unsaturated ketones (see Schemes 1, 8), a library of different heterocycles was prepared in research (Felder and Marzinzik 1998). In preparation for any large-scale synthesis, the availability of starting materials is always considered (Lee and Robinson 1995). For this work, we had to replace Rink amide resin B (Rink 1987), which was used by our colleagues in research for the synthesis of pyrimidine 1 due to its unavailability in large quantities (see Fig. 1). It was replaced with the Rink amide acetamido resin 4, which is well established in peptide amide synthesis (Bernatowicz et al. 1989) and easily accessible. 

Simple acyclic a,/ -unsaturated esters are not reactive in the conjugate addition of dialkylzincs. In contrast, nitro-substituted unsaturated esters68 and malonates69 are applicable for this reaction. Using peptide-based chiral phosphine 66, Hird and Hoveyda realized the Cu-catalyzed conjugate addition of Et2Zn to iV-acyloxazolidinones with excellent enantioselectivity (Scheme 21).70... 

The Ras proteins were then allowed to react with the MIC-modified peptides in stoichiometric amounts. The maleimido group1261 reacts specifically with mercapto groups of proteins by conjugate addition of the thiol to the a, 3-unsaturated carbonyl compound. The Ras mutants reacted smoothly with the MIC modified peptides and in... 

Macrocyclic antibiotics also include a family of thiopeptides, of which thiostrepton (Figure 2.11) is the parent compound and the most complex member. Produced by Streptomyces azureus [59], thiostrepton includes 10 rings, 11 peptide bonds, extensive unsaturation, an imine functionality, a secondary amine, and 17 stereogenic centers [60] it also contains five thiazole rings and one quinoline nucleus. 

A number of nonprotein amino acids with unsaturated side chains have been isolated. Many of these contain alkene side chains, but some alkyne side chains containing amino acids have also been identified. Nonprotein dehydroamino acids do not have an a-stereocenter these amino acids are still classified under this category. Dehydroamino acids are generally biosynthesized by the enzymatic elimination of a leaving group at the /3-carbon. For example, serine and threonine are enzymatically dehydrated to give dehydroalanine and dehydrobutyrine, respectively. A similar biosynthetic pathway is hypothesized for dehydroamino acids found in nonribosomal peptides, such as nodularins and microcystins. ... 

It has been shown that the Claisen rearrangement of lithium enolates of amino acid enynol esters allows the synthesis of very sensitive y, 5-unsaturated amino acids with conjugated enyne side chains.The chelate-enolate Claisen rearrangement has also been applied to the synthesis of unsaturated polyhydroxylated amino acids, polyhydroxylated piperidines, and unsaturated peptides. ... 

Sugars/polysaccharides Unsaturated lipid compounds L-Amino acids/peptides Nucleotides, bases, etc. Biopolymers... 

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