Enantioselective Preparation ofβ2-Amino Acids with Aspartate, Glutamate, Asparagine, and Glutamine Side Chains
| Autor: | Dieter Seebach, Gérald Lelais, Marino A. Campo, Sascha Kopp |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
chemistry.chemical_classification
Chiral auxiliary Stereochemistry Organic Chemistry Enantioselective synthesis Succinic anhydride Biochemistry Catalysis Stereocenter Amino acid Inorganic Chemistry chemistry.chemical_compound chemistry Drug Discovery Asparagine Physical and Theoretical Chemistry Enantiomer Curtius rearrangement |
| Zdroj: | Helvetica Chimica Acta. 87:1545-1560 |
| ISSN: | 1522-2675 0018-019X |
| DOI: | 10.1002/hlca.200490142 |
| Popis: | (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, CbzNHFmocNH, CO2HCO2NH2CONHTrt; 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)! |
| Databáze: | OpenAIRE |
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