Separation of diastereomers

This method is widely used for the resolution of chiral amines and carboxylic acids Analogous methods based on the formation and separation of diastereomers have been developed for other functional groups the precise approach depends on the kind of chem ical reactivity associated with the functional groups present m the molecule... 

Although fractional crystallization has always been the most common method for the separation of diastereomers. When it can be used, binary-phase diagrams for the diastereomeric salts have been used to calculate the efficiency of optical resolution. However, its tediousness and the fact that it is limited to solids prompted a search for other methods. Fractional distillation has given only limited separation, but gas chromatography and preparative liquid chromatography have proved more useful and, in many cases, have supplanted fraetional crystallization, especially where the quantities to be resolved are small. 

Alternatively, to avoid difficult separation of diastereomers 18a and epi-18a, the Fmoc-y9 -amino acid of unlike configuration 26 can be obtained as a single dia-stereoisomer in a three-step reaction sequence via conjugate addition of the Li-amide derived from (S)-N-benzyl-l-phenylethylamine (Davies methodology [113]) to tert-butyl tiglate [105] (Scheme 2.3). 

Funasaki, N., Hada, S., and Neya, S., Conformational effects in reversed-phase liquid chromatographic separation of diastereomers of cyclic dipeptides, Anal. Chem., 65, 1861, 1993. 

Homochiral hydroxyproline 139 served as the starting material for the synthesis of various bicyclic[5.5]hydantoins 140 (Scheme 19). The corresponding amino derivatives 142 were also available by oxidation of the alcohol 141 and reductive amination of the ketone followed by separation of diastereomers by silica gel column chromatography (Equation 19) <2005BML1161>. 

Initial experiments by Tasker (19) were encouraging. He used 3H incorporations and RP-HPLC separations of diastereomers to show very small, and similar, 3H-incorporations and inversions (0.2-0.4%) in the synthesis of [Co(en)2((S)-Thr(Bzl)-GlyOMe)]3+ (1) and /3-[Co... 

Based on the theory, the separation of enantiomers requires a chiral additive to the CE separation buffer, while diastereomers can also be separated without the chiral selector. The majority of chiral CE separations are based on simple or chemically modified cyclodextrins. However, also other additives such as chiral crown ethers, linear oligo- and polysaccharides, macrocyclic antibiotics, chiral calixarenes, chiral ion-pairing agents, and chiral surfactants can be used. Eew non-chiral separation examples for the separation of diastereomers can be found. 

Schulte, M., and Dingenen, J. (2001). Monolithic silica sorbents for the separation of diastereomers by means of simulated moving bed chromatography.. Chromatogr. A 923, 17-25. 

Preparation of Dibenzoyltartramides 20 and Separation of Diastereomers General Procedure 34 CAUTION Benzene is a carcinogen. 

The synthesis of peptides with C-terminal phosphonate moieties results in a mixture of diastereomers when racemic 1-aminoalkylphosphonates are used. In most biological applications, e.g. inhibition of serine protease by peptidyl diphenyl 1-aminoalkylphosphonates, only one diastereomer reacts with the enzyme.14 Pure diastereomers can be obtained by separation of the mixture and simple crystallization frequently works well. Several excellent commercially available HPLC columns are potentially useful for the separation of diastereomers. Alternatively, optically active 1-aminoalkylphosphonic adds can be used as starting materials. 

Scheme 5 Synthesis of L-Ala-L-Alap and Separation of Diastereomers of Z-L-Ala-DL-AlapI71...

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