Tripeptides, 1-step synthesi

Polypeptides (s. a. Tripeptides) —, 1-step synthesis 18, 436 Polyphenyls, synthesis 16, 977 Polyphosphoric acid (s. a. Phosphorus pentoxide/ phosphoric acid) GG"f>0 ... 

The following short descriptions of the steps involved in the synthesis of a tripeptide will demonstrate the complexity of the problem amino acid units. In the later parts of this section we shall describe actual syntheses of well defined oligopeptides by linear elongation reactions and of less well defined polypeptides by fragment condensation. 

First, they compared CSPs 1 and 3 prepared by the two-step solid-phase methodology with their commercially available counterparts (CSPs 2 and 4) obtained by direct reaction of the preformed selector with a silica support. Although no exact data characterizing the surface coverage density for these phases were reported, all of the CSPs separated all four racemates tested equally. These results shown in Table 3-3 subsequently led to the preparation of a series of dipeptide and tripeptide CSPs 5-10 using a similar synthetic approach. Although the majority of these phases exhibited selectivities lower or similar to those of selectors built around a single amino acid (Table 3-3), this study demonstrated that the solid-phase synthesis was a... 

A very similar approach to the same solid-phase supported dendrimers was reported by Portnoy and coworkers by means of iterative Mitsunobu/reduction steps starting with a Wang resin [56]. They used [Gl] (loading 0.62 mmol g ) to [G3] (loading 0.32 mmol g ) dendrimers for synthetic applications. The synthesis of a tripeptide was carried out without previous linker introduction to yield a dendri-... 

The Mitsunobu phosphonate coupling has been adapted to the solid-phase synthesis of peptidyl phosphonates as well.1 2 In this environment, with excess phosphonate, even the more hindered, p-branched esters are formed efficiently. A series of phosphonate tripeptides have been synthesized and used to identify novel thermolysin inhibitors from a small library. (A number of other solid-phase syntheses of phosphonamidate-, 831 phosphonate-, 79 84 and phosphinate-peptides185,86 have been described however, in these instances the phosphorus bond forming steps were performed in solution, prior to solid-phase coupling.)... 

Conversion of the carboxyl group to a more reactive group and coupling are key steps in peptide synthesis. The coupling reaction must occur readily and quantitatively, and with a minimum of racemization of the chiral centers in the molecule. This last criterion is the Achilles heel of many possible coupling sequences. The importance of nonracemization can best be appreciated by an example. Consider synthesis of a tripeptide from three protected... 

Selected examples are shown in Scheme 5.31. For example, the product 51b was obtained in 63% yield with a high d.r. ratio of 14 1 and high enantioselectivity of 95% ee. This multi-step one-pot synthesis has also been applied to the synthesis of, e.g., tripeptides and an L-tkreo-/Miydroxyasparagine derivative [58]. 

Figures 2.2 and 2.3 also show that, starting with a single substance, the resin, used as solid support, the number of compounds is tripled after each coupling step first 3x1 = 3 (=3 ) resin bound amino acids, then 3x3 = 9 (= 32) resin bound dipeptides, then 3 x 9 = 27 (= 33) resin bound tripeptides and, finally, 3 x 27 = 81 (=34) tetrapeptides are formed. This means that the number of products increases exponentially as the synthesis proceeds. If, instead of three monomers, 20 different amino acids are used in the synthesis, the number of peptides in each coupling step is increased by a factor of 20. The total number of the synthesized peptides can be expressed by a simple formula 20", where n is the number of amino acid residues in the peptides.

To complete the synthesis, it is necessary only to remove the protecting groups. The BOC group is removed by treatment with aqueous acid. This reaction occurs under very mild conditions that do not also hydrolyze the ester group. Note that this dipeptide, deprotected at the N-terminal, can be reacted with another N-protected, carboxyl-activated amino acid to produce a tripeptide. These steps can be repeated to produce a tetrapeptide, and so on. 

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