Amino acid experimental procedures, racemization

Standard solid-phase peptide synthesis requires the first (C-terminal) amino acid to be esterified with a polymeric alcohol. Partial racemization can occur during the esterification of N-protected amino acids with Wang resin or hydroxymethyl polystyrene [200,201]. /V-Fmoc amino acids are particularly problematic because the bases required to catalyze the acylation of alcohols can also lead to deprotection. A comparative study of various esterification methods for the attachment of Fmoc amino acids to Wang resin [202] showed that the highest loadings with minimal racemization can be achieved under Mitsunobu conditions or by activation with 2,6-dichloroben-zoyl chloride (Experimental Procedure 13.5). iV-Fmoc amino acid fluorides in the presence of DMAP also proved suitable for the racemization-free esterification of Wang resin (Entry 1, Table 13.13). The most extensive racemization was observed when DMF or THF was used as solvent, whereas little or no racemization occurred in toluene or DCM [203]. 

Since the discovery by Carpino et al.f l that A -Pbf-protected amino acids can be activated even as acid chlorides, such derivatives have been found to be well suited for the acylation of sterically demanding amino components (for details and experimental procedures, see Section 3.3.1). Oxazolone formation is prevented by this type of N -protection, racemization is not observed during activation and coupling.In line with these findings, further sulfonamide derivatives have been proposed such as l,3-benzothiazol-2-ylsulfonyl (Bts, 1Q4),[659,660] 5-methyl-l,3,4-thiadiazol-2-ylsulfonyl (105),f l 2-nitrophenylsulfonyl (oNbs, 4-nitrophenylsulfonyl (107),t l and 2,4-dinitrophenylsulfonyl group (108) (Scheme 49).f l... 

Since (Z)- and ( )-stereoisomers of unsaturated oxazolones can be obtained using appropriate isomerization procedures, cis and trans isomers of cyclopropane derivatives can be obtained in a stereoselective manner, although special care must be taken with experimental conditions to obtain the best stereoselectivity. Both racemic cis- and fraui-l-amino-2-phenylcyclopropanecarboxylic acid 641 and 644 have been obtained from the corresponding (Z)- or ( )-4-benzylidene-2-phenyl-5(4//)-oxazolone 621 and 642 using diazomethane. Care was taken to affect the... 

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