Enantioselective Preparation of β2-Amino Acids with Aspartate, Glutamate, Asparagine, and Glutamine Side Chains

✍ Scribed by Gérald Lelais; Marino A. Campo; Sascha Kopp; Dieter Seebach

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: German
• Weight: 304 KB
• Volume: 87
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200490142

✦ Synopsis

S)-b 2 -Homoamino acids with the side chains of Asp, Glu, Asn, and Gln have been prepared and suitably protected (N-Fmoc, CO 2 t Bu, 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 (CO 2 H > CO 2 t Bu, CO 2 Bn > CO 2 H, CbzNH 3 FmocNH, CO 2 H 3 CO 2 NH 2 3 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 b 2 hAsn and of a b 2 hGln 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)!