Diastereomeric dipeptides

Racemic cw-l-amino-2-phenylcyclohexanecarboxylic acid 693 can be prepared by Diels-Alder reaction of (Z)-4-benzyhdene-2-phenyl-5(47/)-oxazolone 621 and butadiene in an analogous manner. Coupling A-tert-butyloxycarbonyl-L-proline with 693 yielded diastereomeric dipeptides that were separated chromatographi-cally. The behavior of the individual dipeptides was studied as a means to effect p-tum modulation by such cyclohexane analogues of phenylalanine. ... 

It is well known that derivatives of a-amino acids, especially the esters, can undergo cyclodimerization to form piperazine-2,5-diones. The stereochemistry of such self-condensation of initial stages but increasing amounts of the trans product were formed later. The results have been interpreted as reflecting the difference in the rates of cyclization of the two diastereomeric dipeptide esters. 

Aspartame is a diastereomeric dipeptide ester, with the two asymmetric carbons ( ) being derived from (Z)-amino acids. The other three diastereomers of aspartame (the D.D-, D,L- and L,D- diastereomers) are not sweet. The three dimensional structure of aspartame in the zwitterionic form can be depicted in the following stereoscopic figure ... 

Negative ionization is also very sensitive to stereochemical effects. Winkler and Stahl [38] were thus able to differentiate diastereomeric diols. More recently, we [65] were able to distinguish diastereomeric dipeptides R-R and R-S by the variations in the abundance of losses of benzyl radical and of acetamide (Fig. 7). 

Scheme 1.355). Catalytic reduction of 1384 produced a 10 1 mixture of dia-stereomers 1385 and 1386 quantitatively. Hydrolysis of this diastereomeric mixture with lithium hydroperoxide gave the acids 1387 and 1388, which were immediately coupled with serine methyl ester to afford the diastereomeric dipeptides 1389 and 1390. Hydrolysis of 1385 and 1386 with lithium hydroxide also gave 1387 and 1388 but effected significant epimerization at C(30). The diastereomers were separated, and 1389 was cyclized to 57 with Burgess reagent. ... 

Chiral derivatization of the amino group has included the formation of diastereomeric amides, ureas, thioureas and isoindoles, the carboxylic acid group being either protected or left unreacted. Diastereomeric dipeptides have been prepared using a range of N-substituted activated amino acids, e.g. S( — )-N-(trifluoroacetyl)propyl chloride (11), L-leucine-N-carboxyanhydride (45) and t-butoxycarbonyl-L-leucine N-hydroxysuednimide ester (55). (See Section 4.6.2 for reagent structures). 

Enantiomeric and diastereomeric dipeptides (on Chiralplate) Solvents and /i/f/given in Table 5 0.1% Ninhydrin 19,62... 

The successful separation of dipeptide diastereomers has been reported by Wieland and Bende (14), Taschner et al. (15), and Pravada et al. (16) either as the free peptides or as the N-protected methyl esters. Hubert and Dellacherie (5) separated diastereomeric p-nitrophenyl (Np) esters of N-protected di- and tripeptides starting from pure L-methionine and DL-alanine, they synthesized Np-S-L-Met-DL-Ala-O-Np and Np-S-L-Met-L-Met-DL-Ala-O-Np. The separation was achieved on silica gel F254 precoated (Merck) plates. TLC separation of diastereomeric dipeptides has been well documented by Arendt et al. (17) and Lepri et al. (18). 

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