Tripeptides solid phase synthesis

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... 

Tripeptides with N-terminal anthranilic acid part were used as starting materials in the solid-phase synthesis carried out on TentaGel resin to prepare 1,4,11,1 l -tetrahydro-2//-pyrazino[2,l-3]quinazoline-3,6-diones with various N-l and N-3 substituents <2003EPP1471066>. Tandem cyclization from [6+0] atom fragments took place in the solid-phase synthesis of 143 from 142. Intermediate 141 was built on bromoacetal resin (Scheme 17) <1998JOC3162>. 

Once it is part of a cyclic dipeptide, the prolyl residue becomes susceptible to enantiomerization by base (see Section 7.22). The implication of the tendency of dipeptide esters to form piperazine-2,5-diones is that their amino groups cannot be left unprotonated for any length of time. The problem arises during neutralization after acidolysis of a Boc-dipeptide ester and after removal of an Fmoc group from an Fmoc-dipeptide ester by piperidine or other secondary amine. The problem is so severe with proline that a synthesis involving deprotection of Fmoc-Lys(Z)-Pro-OBzl produced only the cyclic dipeptide and no linear tripeptide. The problem surfaces in solid-phase synthesis after incorporation of the second residue of a chain that is bound to the support by a benzyl-ester type linkage. There is also the added difficulty that hydroxymethyl groups are liberated, and they can be the source of other side reactions. 

Dragovich, P. S., Zhou, R., Skalitzky, D. J., Fuhrman, S. A., Patick, A. K., Ford, . E., Meador, J. W., Ill, Worland, S. T. (1999) Solid-phase synthesis of irreversible human rhinovirus 3C protease inhibitors. Part 1 optimization of tripeptides incorporating N-terminal amides. Bioorg Med Chem 7, 589-598. 

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.)... 

Polymyxin B, (Section 16.1.6) is a cyclic heptapeptide with a pendent tripeptide segment that has topical antibiotic properties. The solid-phase synthesis is carried out with appropriate side-chain protections. The linear heptapeptide is removed from the resin and cyclized to yield the polymyxin B,. The synthesis of the peptidomimetic (S)-6-methyloctanoic acid is also outlined.136 ... 

Fig. 11. Solid-phase synthesis of bis-cyclic thioureas and bis-cychc guanidines from resin-bound reduced tripeptides.

Typical solid phase synthesis protocols were employed to assemble the tripeptide building blocks into C-link AFGP glycopolymers. The method is illustrated in Scheme 3. 

The solid phase synthesis of many organic molecules utilizes carbodiimide mediated reactions. An example is the synthesis of l,4-benzodiazepine-2,5-dione using EDCCl in NMP in a key synthesis step. Often carbodiimides are used in the synthesis of complex proteins. A recent example is the synthesis of the tripeptide backbone of the novel immunosuppressent sanglifehrin A. In the synthesis of the marine alkaloid, variolin B, the formation of an annelated pyrimidine ring is achieved using a carbodiimide mediated cyclization process. 

Figure 2 The structure of a tripeptide and the corresponding monomer for solid-phase synthesis, contrasted with trimers and monomers for three other oligomer libraries prepared from bifunctional monomers...

Solid-phase synthesis has been shown to be ideal for the preparation of hbraries of potential drugs, and the advantages involved are likely to pertain to platinum drugs. In this respect, our group reported the solid-phase synthesis of dichloroplatinum(II) tripeptide complexes and dinuclear platinum(II) complexes. Using this technique, a library of complexes was generated in an automated synthesizer and conveniently screened for cytotoxicity via an adapted MTT assay. ... 

Merrifield automated solid-phase synthesis of a tripeptide... 

On the basis of this cleft-type scaffold, Anslyn s group prepared a chemo-sensor library to discover a sophisticated nucleotide receptor possessing high selectivity toward ATP [32]. The attachment of the scaffold on Wang resin for solid phase synthesis, followed by tethering two tripeptide chains branch-... 

Yasukata, T. et al.. An efficient and practical method for solid-phase synthesis of tripeptide-bearing glycopeptide anhbiohcs combinatorial paraUel synthesis of carboxamide derivatives of chlotoorien-tacin B, Bioorg. Med. Chem. Lett., 12, 3033, 2002. 

Esser, C.K., Kevin, N.J., Yates, N.A. and Chapman, K.T., Solid-phase synthesis of a N-carboxyalkyl tripeptide combinatorial library, Bioorg. Med. Chem. Lett., 20 (1997) 2639-2644. 

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