Enantioselective Preparation of β2‐Amino Acids with Aspartate,Glutamate, Asparagine,and Glutamine Side Chains |
| |
Authors: | Grald Lelais MarinoA Campo Sascha Kopp Dieter Seebach |
| |
Institution: | Gérald Lelais,Marino A. Campo,Sascha Kopp,Dieter Seebach |
| |
Abstract: | (S)‐β2‐Homoamino acids with the side chains of Asp, Glu, Asn, and Gln have been prepared and suitably protected (N‐Fmoc, CO2tBu, CONHTrt) for solid‐phase peptide syntheses. The key steps of the syntheses are: N‐acylation of 5,5‐diphenyl‐4‐isopropyl‐1,3‐oxazolidin‐2‐one (DIOZ) with succinic and glutaric anhydrides (Scheme 2), alkylation of the corresponding Li‐enolates with benzyl iodoacetate and Curtius degradation (Scheme 4), and removal of the chiral auxiliary (Scheme 5). In addition, numerous functional‐group manipulations (CO2H?CO2tBu, CO2Bn?CO2H, CbzNH→FmocNH, CO2H→CO2NH2→CONHTrt; Schemes 2, 4, 5, and 6) were necessary, in order to arrive at the four target structures. The configurational assignments were confirmed by X‐ray crystal‐structure determinations (Scheme 2 and Fig. 3). The enantiomeric purities of a β2hAsn and of a β2hGln derivative were determined by HPLC on a Chiralcel column to be 99.7 : 0.3 and >99 : 1, respectively (Fig. 4). Notably, it took up to twelve steps to prepare a suitably protected trifunctional product with a single stereogenic center (overall yield of 10% from DIOZ and succinic anhydride)! |
| |
Keywords: | |
|
|