Separation of Z and E Isomers

Cis-trans isomers of peptides can be separated by several techniques including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and capillary electrophoresis. 

In organic solvents, protected peptides containing clustered proline residues often display multiplicity of spots which correspond to slowly interconverting Xaa-Pro isomers, however, the resolution strongly depends on the mixture composition as well as peptide sequence. As an example, Boc-Pro-Pro-OMe appears as 

Low-temperature HPLC separation of peptides allows the separation of cis and trans isomers of constrained peptides such as the intramolecular disulfide of Cys-Leu-Pro-Arg-Glu-Pro-Gly-Leu-Cys which gave two peaks at 0 °C coalescing at higher temperature (Fig. 8.10). The resolution was also strongly dependent on the solvent of injection since HPLC chromatograms obtained from a concentrated LiCl/TFE solution of peptides showed significant modifications [68], When the rate of interconversion is sufficiently slow relative to experimental time, both isomers of smaller and nonconstrained peptides can be separated with excellent resolution at 0 °C [69,70]. 

Capillary electrophoresis is also able to distinguish both cis and trans isomers of linear peptides [67] and thioxopeptides irradiated at 254 nm [25,71]. Although capillary electrophoresis is anticipated to separate products by charge, and charge itself would not be affected by conformational changes, this may be explained by the distinct solvation of conformers which therefore have different abilities to be ionized in solution. 

Models and Mimics for the Study of Amide CTI Towards Multiple CTI Pathways 

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The first total synthesis of simmondsin (73) a naturally occurring cyanoglucoside has been achieved from L-quebrachitoI and D-glucose. The key steps involve the deoxygenation of epoxide (74) with lithium aluminium hydride, cyanomethylation of the ketone (75) by Homer-Emmons alkenylation (with separation of Z and E isomers) and glycosidation of alcohol (76) with 2,3,4,6-tetra-O-acetyl-P-D-glucosyl trichloroacetimidate. 

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