Synthesis of dipeptides

Higher peptides are prepared m an analogous way by a direct extension of the logic just outlined for the synthesis of dipeptides... 

The addition of titanated 2-methylpropenamides to 2-(ter/-butoxycarbonylamino)a]dehydes was investigated during the synthesis of dipeptide isosteres and was shown to exhibit low selectivity only93,94. 

Table 20 Synthesis of dipeptides from aminocarbenes and a-aminoesters...

Scheme 7.5 Enzymatic synthesis of dipeptides on solid phase.

A few vinylzinc reagents have been added to aldehydes in the presence of chiral sulfur-containing ligands. As an example, Seto et al. reported, in 2005, the synthesis of dipeptide A-acylethylenediamine-based ligands by parallel... 

The reaction of 5a-bromo-a-tocopherol (46) with amines was further elaborated into a procedure to use this compound as a protecting group Toe for amines and amino acids (Fig. 6.35).62 The protection effect was due to a steric blocking of the amino function by the bulky tocopheryl moiety rather than due to conversion into a non-nucleophilic amide derivative, and the Toc-protected amino acids were employed in the synthesis of dipeptides according to the dicyclohexylcarbodiimide (DCC) coupling method.64 The overall yield of the reaction sequence was reported to be largely dependent on the coupling reaction, since both installation and removal of the... 

FIGURE 6.35 5a-Bromo-o -tocopherol (46) as auxiliary in the synthesis of dipeptides the Toe protecting group. 

The synthesis of dipeptides under the conditions found on primeval Earth appears highly likely. The discovery that these small molecules can act as catalysts makes it possible to discuss their being involved in basic synthetic reactions occurring in an (as yet hypothetical) RNA world (Weber and Pizzarello, 2006). 

K Takeda, A Ayabe, M Suzuki, Y Konda, Y Harigaya. An improved method for the synthesis of active esters of A-protected amino acids and subsequent synthesis of dipeptides, (isopropenyl mixed carbonates) Synthesis 689, 1991. 

M Schutkowski, C Mrestani-Klaus, K Neubert. Synthesis of dipeptide 4-nitroanilides containing non-proteinogenic amino acids, (p-nitrophenylisocyanatc) Int J Pept Prot Res 45, 257, 1995. 

Eichhorn, U., Bommarius, A. S., Drauz, K., and Jakubke, H.-D. (1997). Synthesis of dipeptides by suspension-to-suspension conversion via thermolysin catalysis from analytical to preparative scale. J. Pept. Sci., 3, 245-51. 

It has recently been demonstrated that a stereoselective synthesis of dipeptides by hydrogenation of the corresponding monodehydropeptides (N-protected free acids or methyl esters) is possible. In this reaction, chiral catalysts, for example BPPM (13), in the form of a Wilkinson complex have been used. These are superior to the corresponding DIOP complexes (DIOP = P,P -[2,2-dimethyl-l,3-dioxolane-4,5-bis(methylene)]bis(diphenylphosphane). A d.s. value of 90—99% was generally obtained 49 ... 

Only a limited number of examples are known of applications of thietanes in organic synthesis. Prominent among these examples would be electrophilic ring opening reactions leading to polyfunctional sulfur compounds (33)-(37), utilization of 3-thietanones (55) and metal complexes (87) derived therefrom as oxyallyl zwitterion equivalents in cycloaddition reactions, synthesis of dipeptide (63) with a /3-thiolactone, Raney nickel desulfurization of thietanes (e.g. 120 cf. Table 7) as a route to gem-dimethyl compounds, and desulfurization of thietanes (e.g. 17) in the synthesis of cyclopropanes (also see Table 7). 

Fig. 7. Synthesis of dipeptides using organochromium(O) carbenes ( indicates known chiral center indicates a new chiral center).

In contrast, the isourea-mediated p-elimination method from Thr peptides gave a mixture of Z- and E-isomers in a 3 2 ratio. 104 Similarly to AAla, peptides containing AAbu can also be synthesized by N-hydroxylation/dehydration 147 or by N-chlorination/dehydrochlorina-tion. 122-124 Another method, reported by Smelka et al. 148 involves the synthesis of dipeptides 60 with a C-terminal AAbu by condensing the Na-protected a-amino acid amides 58 with the a-oxo acid 59 (Scheme 20). The ratio of Z/E-isomers is 10 1. We have used Miller s method to prepare peptides containing AAbu. 351... 

Dipeptides with C-terminal 1-aminoalkylphosphonic acids such as L-Ala-L-Alap (8), can be coupled to another amino acid active ester using the same methods used in the synthesis of dipeptides. The dipeptide can be extended from the N-terminal up to hexapeptides. Generally, the yield for each step is >60% J7 ... 

Scheme 15 Synthesis of Dipeptides of Diphenyl Pyrrolidine-2-phosphonate[431...

Scheme 17 Synthesis of Dipeptides of 1-Aminomethylphosphonic Acids from Their Diphenyl Esters1451...

Synthesis of amides and peptidesThe reagent, prepared as shown, converts carboxylic acids into 3-acyl-2-oxazolones (2), which acylate amines under mild conditions in high yield. A one-step synthesis of dipeptides in high yields is possible... 

The kinetics of this equilibrium-controlled reaction have been worked out in detail (Oyama, 1981a,b). From all the possible ways to shift the equilibrium in favor of synthesis of dipeptide ... 

Peptides of aminoalkanephosphonic acids (Phosphono-peptides 4,are now receiving considerable interest because some representatives of this class were found to repress,bacterial growth at very low concentration levels 1. Literature data on the synthesis of dipeptides containing aminoalkylphosphonic acids are scarce and very little information is avaiable,on blocking and deblocking of the phosphonate moiety ... 

In this communication we report synthesis of dipeptides containing P-terminal aminoalkylphosphonic acids related structurally to glycine,alanine,nor-vallne,valine, leucine,phenylglycine and phenylalanine,while the N-terminal residues include glycine,alanine,valine,leucine,pro line,methionine,beta -alanine,phenylalanine, tyrosine, lysine and glutamine. 

Asymmetric aldol reactions may also be controlled with high diasteroselectivity, but this time for the anti isomer, in reactions of A -tosyl derivatives of esters derived from 7 (eq 3). Diastereoselectivities of up to 99 1 were achieved in the illustrated titanium(IV)-mediated reaction, which has been employed for the synthesis of dipeptide isosteres for incorporation into pharmaceutical building blocks.The selectivity reverses... 

Senten K, Daniels L, Van der Veken P, De Meester 1, Lambeir 69. A-M, Scharpe S, Haemers A, Augustyns K. Rapid parallel synthesis of dipeptide diphenyl phosphonate esters as inhibitors of dipeptidyl peptidases. J. Comb. Chem. 2003 5 336-344. 70. 

Pseudoprolines (Synthesis of Dipeptide Building Units from Serine and Threonine)... 

Scheme 10 Synthesis of Dipeptides Using the U-4CR and Cleavable Aldehydesl ...

An optimised solid-phase method for the generation of diverse a-amino-alkyl or -aryl phosphonates derived from peptides and polymer-assisted solution-phase parallel synthesis of dipeptide p-nitroanilides and dipeptide diphenyl phosphonates have been reported. A modular method for the construction of polypeptides containing the Phe-Arg phosphinic acid isostere has been described. A novel methodology for the solid-phase synthesis of phosphinic peptides has been developed in which the phosphorus-carbon bond was formed... 

An RNA Diels-Alderase ribozyme recently developed that catalyses the formation of carbon-carbon bonds between a tethered anthracene diene and a biotinylated maleimide dienophile. The ribozyme active site has been further characterised by chemical substitution of the diene and dienophile. It was shown that the diene must be an anthracene, and substitution only at specific sites is permitted. The dienophile must be a maleimide with an unsubstituted double bond. The RNA-diene interaction was found to be governed preferentially by stacking interactions. A ribozyme has been selected that catalyses the synthesis of dipeptides using an aminoacyl-adenylate substrate. The ribozyme catalysed the formation of 30 different dipeptides, many with rates similar to that of the Met-Phe dipeptide used in the selection process. 

Prepared from catechol and phosphorus trichloride via o-phenylenephosphoro-chloridite. Used in peptide synthesis for the direct interaction of the two com-ponents (compare tetraethyl pyrophosphite). Synthesis of dipeptides is satisfactory, but extensive racemization occurs when N-acyl peptides are employed. 

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