Dipeptide Schiff bases

The selected examples by Cole et al. [120] and Shimizu et al. [121] reported the parallel synthesis of a small library of solid supported dipeptide Schiff bases as ligands for the Ti-catalyzed enantioselective addition of trimethylsilyl cyanide to meso epoxides, and the determination of their catalytic activity on different substrates. The catalyzed addition reaction and the general structure of the dipeptide ligands are shown in Figure 7.15. 

The chemistry already described is reproduced by numerous ligands that have not specifically been addressed in the previous discussion. The V-salicylidenehydrazides (Scheme 4.18a) and related compounds provide a good example. The structure [76] of a typical complex, represented in Scheme 4.18b, is not very different from that proposed for the solution structures of dipeptide complexes (Scheme 4.17). Interestingly, other similar complexes, based on Schiff base-derived ligands, form dimeric [VO]2 core complexes (Scheme 4.1) via two long ( 2.4 A) VO bonds [2], The cyclic core is not necessary for dimer formation, and a dimer can form via a linear VOV bond [77], These complexes otherwise are not significantly different in their vanadium coordination from that depicted in Scheme 4.18b. 

An example of diastereoface differentiation is provided in an asymmetric synthesis of the dipeptide Ala-Ala [70]. The element of chirality is that of one of the alanine groups, and the faces are those of a Schiff base, > C=N—. The material undergoing a catalytic reduction is the isobutyl ester of the benzylamine Schiff base of N-pyruvoyl-(5)-alanine, 54. The ratio of R S (55) to S S dipeptide was 82 18 for an optical purity of 64%. 

Several years later, more useful catalysts were described these were prepared from amino acids or dipeptides via their Schiff bases with 2-naphthol-l-carboxalde-hyde [13], The catalyst giving the highest induction for this reaction was prepared from the Schiff base 48 and trimethylaluminum. This catalyst resulted in moderate induction with several aldehydes including the three shown in Sch. 6. 

Due to their increased reactivity toward nucleophiles, dipeptide a-phenacyl esters are prone to piperazine-2,5-dione (DKP) formation. Coupling of amino acid phenacyl esters with an activated carboxy component for dipeptide synthesis often results in substantial cyclization of the amino acid phenacyl esters via Schiff base formation (Scheme... 

Another catalyst system which shows a good performance in catalytic activity as well as asymmetric induction is formed in situ, starting from titanium(IV) alk-oxides and the Schiff bases of acyclic dipeptides 55a/b. 

Groups 5 and 6. The complexation of Vv02+ by the Schiff base N,N -ethylenebis(pyridoxyl-aminato) was followed by 111 and 51V NMR spectroscopy.1121 13C, 14N and 51V NMR spectra were used to follow reactions of vanadate(V) with dipeptides (Val-Glu, Ala-Gly etc.).1122 The reaction of TaF5... 

The structural characterization of the Schiff base AG adduct of DCL and the dipeptide (KF lys-phe) B shown in Figure 10.15. This adduct displayed protonated molecular ions at m/z 747 and m/z 749 corresponding to two chlorine isotopes with an intensity ratio of 3 2 (Figure 10.15B). Data that corresponded to the peak at 18.87 minutes shows a similar spectrum (data not shown). The product ions at m/z 729 and m/z 711 correspond to the consecutive neutral losses of water molecules from the molecular ion. The... 

Formyl-5-hydroxy[2.2]paracyclophane (153) was used as a chiral auxiliary in the synthesis of a-amino acids [98]. The reported enantiomeric excess was in the range of 90-98%. Racemic 153 was first prepared by Hopf and Barrett [99]. To separate the enantiomers, their Schiff bases with the dipeptide (S)valyl-(S)valine was prepared. The diastereomeric copper(II) complexes of this compound show different solubility in 2-propanol. Alternatively they can be separ-... 

In a similar manner, we synthesized dipeptides (Scheme 6) and their hydroxy analogs (depsipeptide unit) (Scheme 7) starting from the Schiff bases of a-amino acid esters (14). Optically pure dipeptides were synthesized via separation of the two diastereomers of the azido-3-lactam by HPLC as typified in Scheme 8. It turned out that no racemizatlon at all took place during the ring opening... 

Since a 3-lactam derived from the Schiff base of an a-amino acid ester was thus proved to be the synthetic equivalent of dipeptide, we prepared tripeptide and tetrapeptide synthons involving one or two 3-lactams, which were further submitted to hy-drogenolysis to give the corresponding tri- and tetrapeptides (Scheme 9)(16). 

Lisinoprii has been prepared by the scheme outlined in Figure 1 (7,8). The dipeptide, Ng-trifluoroacetyl-L-lysyl-L-proline (D is subjected to reductive alkyiation with ethyl 2-oxo-4-phenylbutanoate over Raney Nickel via a Schiff base to yield a diastereomeric mixture 4 (SSS and RSS). Hydrolysis of the N -trifluoroacetyl moiety and saponification of the ethyl ester followed by crystallization in ethanol/water and final recrystallization in water yield lisinopril (SSS, 5) of greater than 98% purity in about 65% yield (based on In addition to this synthetic route, others have also been described in the literature (9-12). 

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