Guanidine modified derivatives

Several guanidine-modified tetrapeptides have been isolated from marine invertebrates, in particular marine sponges. Nazumamide A (39) has been isolated from the sponge Theondla sp. and identified by analysis of spectroscopic data [60] as well as by X-ray diffraction analysis of a nazumamide A-human thrombin complex [61[. Nazumamide A has been synthesized by conventional peptide synthesis [62[. A series of nazumamide derivatives have been prepared via combinatorial synthesis [63[. 

The functions of the guanidine-modifying enzymes further subdivide the family into three distinct groups hydrolases, dihydrolases, and amidinotransferases. Hydrolases catalyze the hydrolysis of guanidine derivatives to form ureido compounds, whereas dihydrolases catalyze a hydrolysis reaction to yield a primary amine, ammonia, and bicarbonate (or carbon dioxide). The amidinotransferases transfer an amidino group from one substrate to an amine. Although these are distinct reactions, they are characterized by common structural and mechanistic themes. 

In fact, the authors found that in different proteins, the second derivative spectra below 270 nm were essentially the same as the second derivative spectrum of phenylalanine (Ichikawa and Terada, 1979). The absorption at certain peaks and troughs of the second derivative spectrum of phenylalanine are found dependent on the microenvironment of the phenylalanine. Denaturation of the proteins by urea or guanidine modifies the intensities of the spectral bands of phenylalanine without inducing a significant shift in their positions. Table 1.3 shows the difference between peaks and troughs in the second derivative spectrum of phenylalanine under various conditions and Table 1.4 shows the difference observed for four proteins in the native and denatured states. 

Helferich and Kosch first prepared l-/3-D-glucopyranosyl-2-meth-ylpseudothiourea,90 which Maekawa and Liener used for modifying trypsin (EC 3.4.4.4) in an effort to define the role of amino groups in the activity of the enzyme.91 This reagent reacts with amino groups to form a guanidine derivative, as shown in Scheme 13. 

Modified guanidines 3 efficiently catalyzed the asymmetric Michael addition of a prochiral glycine derivatives with acrylate, acrylonitrile and methyl vinyl ketone under simple and mild conditions. Remarkably, both product formation and enantioselectivity were dramatically improved using solvent-free conditions (Scheme 12) [34]. The addition of alcohols to methyl propiolate was performed using fluorous phosphines such as P[(CH2)2 (CF2)7 CF3]3 and again better yields of 99% have been obtained under solvent-free conditions. Toluene was added to efficiently separate the product from the solid catalyst, which was then reused without loss of activity [35],... 

While this catalyst could not be applied to the Strecker reaction, Lipton was able to modify this species and was the first to report an asymmetrically catalyzed Strecker reaction. He reasoned the imidazole did not possess sufficient basicity and prepared the corresponding guanidine derivative, cyclo[(5)-phenylalanyl-(5)-norarginyl] 56. 

Guanidines. An exceptionally mild alkylation method for guanidine is the use of a modified Mitsunobu reagent combination and an alcohol on its A,A -diBoc derivative. 

Isobe, T, Fukuda, K. and Ishikawa, T. (2000) Modified guanidines as potential chiral superbases. 1. Preparation of 1,3-disubstituted 2-iminoimidazolidines and the related guanidines through chloroamidine derivatives. The Journal of Organic Chemistry, 65, 7770-7773 ... 

The concept of bifunctional catalysis as advanced for the natural cinchona alkaloids and cuprei(di)nes has resulted in the design and synthesis of a range of new cinchona derivatives. The major part of these novel organocatalysts are urea and thiourea cinchona derivatives together with cinchona alkaloids modified with, for example, a sulfonamide, squaramide, or guanidine group (Figure 6.8). 

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