Dipeptides, irradiation

Endotoxin and Muramyl Dipeptide Derivatives. Bacterial cell wall constituents such as the Hpopolysaccharide endotoxin and muramyl dipeptide, which stimulate host defense systems, show radioprotective activity in animals (204). Although endotoxin is most effective when given - 24 h before irradiation, it provides some protection when adrninistered shortiy before and even after radiation exposure. Endotoxin s radioprotective activity is probably related to its Hpid component, and some of its properties may result from PG and leukotriene induction (204). 

The amide functionality plays an important role in the physical and chemical properties of proteins and peptides, especially in their ability to be involved in the photoinduced electron transfer process. Polyamides and proteins are known to take part in the biological electron transport mechanism for oxidation-reduction and photosynthesis processes. Therefore studies of the photochemistry of proteins or peptides are very important. Irradiation (at 254 nm) of the simplest dipeptide, glycylglycine, in aqueous solution affords carbon dioxide, ammonia and acetamide in relatively high yields and quantum yield (0.44)202 (equation 147). The reaction mechanism is thought to involve an electron transfer process. The isolation of intermediates such as IV-hydroxymethylacetamide and 7V-glycylglycyl-methyl acetamide confirmed the electron-transfer initiated free radical processes203 (equation 148). 

There are relatively few examples of the preparation of six-membered rings, which require a blocking of both the y- and d-positions. This function may be fulfilled by an aromatic ring or by an amide group. Naphthalene derivatives have been prepared by the former approach [17]. The latter approach enables convenient access to different d-lactams [18]. Scheme 8a shows an interesting application - the preparation of /3-turn peptide mimetics [19]. Dipeptides 41, prepared from L-benzoylalanine and L-proline, can be stereoselectively cyclized on irradiation, providing the bicyclic lactams 42 in good yields. 

Numerous ESR studies of the photodamage effect on biologically important molecules have been reported in recent years. Brustad (377) studied the UV-irradiation of the enzyme trypsin and found a linear correlation of the loss of enzyme activity with concentrations of the photoproduced radical. Leterrier and Douzou (378) have applied ESR techniques to study the mechanism of the photoreduction of flabin mononucleotide. A number of investigations deal with photodamage of aliphatic amino acids, glycine peptides, dipeptides, and alanine peptides (379-383). John et al. 

Irradiation of Fischer carbene complexes generates, by insertion of carbon monoxide, a metal-bound ketene intermediate. Photolytic reactions of carbene complexes are synthetically attractive, in that the reaction conditions are mild and the reactions of ketene intermediates with a variety of reagents is of significant scope. A low concentration of metal-bound ketene is probably obtained and in the absence of a nucleophile, the starting material can usually be recovered even after prolonged irradiation. The ketene intermediates are readily trapped with nucleophiles for example, dipeptides are formed in excellent yield and with very high diastereoselectivity upon irradiation of optically active carbenes in the presence of natural or urmatural a-amino acids (Scheme 28). Dipeptides and PEG-supported amino acids and dipeptides can also be used as nucleophiles. 

The photolytic oxaziridine rearrangement was used by Wenglowsky and Hegedus to prepare sterically demanding dipeptides <1998JA12468>. For example, irradiation of oxaziridine 22 afforded amide 23 in 35% yield. 

The dipeptide sweetener aspartame has been synthesized via an oxaziridine, which was rearranged by irradiation with UV light (equation 26). ... 

Figure 14 Profiling of aspartyl protease activity, (a) Catalytic mechanism of aspartyl proteases that cleave peptide bonds via activation of a water molecule, (b) A hydroxyethylene dipeptide isostere-based probe binds tightly to the active site and gets covalently attached via UV irradiation.

Sauer et al have reported the photochemical reactivity of some dipeptides. To exemplify the reactivity of such systems the dipeptide (68) has been chosen. This, on irradiation, undergoes conversipn into the products (69) and (70) in the ratios shown. The reaction involves a 1,6-hydrogen abstraction and rotation within the resultant 1,5-biradical is hindered. Temperature effects... 

Species stable after 7-irradiating approximately 200 mg/ml of the corresponding dipeptide in ice plugs at —196 °C to a dose of about 5 kGy and annealing to -50°C. 

The structure of a thymine dipeptide (Fig. 6.24) and its absorption spectrum before and after irradiation at 257 nm is shown below (Fig. 6.25). 

Asymmetric synethesis of dipeptides. The chromium amino-carbcnc 1, pcntacar-bonyl [(R-l-aza-2,2-dimcthy]-3-oxa-5-phenylcyclopentyl)(methyl)carbcne]chromium(0), derived from (R)-alaninc, undergoes carbonylative coupling with amino esters under irradiation (visible light) at 0° to form (S,S)-dipcptidcs with high diastereoselectivity. 

Another group followed a similar approach and investigated the photochemical behavior of some dipeptides consisting of the L-)9-benzoyl alanine and V-substituted glycines. The irradiation of the iminodiacetic acid derivative 30 provided the 5-lactam 31 in good yields and with an excellent diastereoselectivity. If sarcosine is used instead of iminodiacetic acid, the cyclization proceeds with lower regioselectivity [18]. Obviously, only reactants with cyclic residues such as 28 or symmetrically substituted compounds such as 30 ensure a highly selective cyclization (Scheme 6). 

Figure 1. Light-directed parallel synthesis of two dipeptides from two amino acids in two irradiation...

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