Peptide synthesis, Leuchs anhydrides

Fig. 5.2 Peptide synthesis using Leuchs anhydrides amino acid 1 (with residue Ri) is reacted with phosgene to give the Leuchs anhydride. This reacts with amino acid 2 (residue R2) to give the peptide carbamate. The dipeptide is obtained after cleavage of C02...

For efficient peptide bond formation acid halides azides 2,b l and Leuchs anhydridesb l were employed as the first activated species in peptide synthesis. Since then, besides considerable improvements to the azide (see Section 3.1) as well as the V-carboxyanhydride 7 procedure d (sgg Section 3.4.3), the methods have evolved over decades along a few basic principles as outlined in Scheme 2. The symmetrical the mixed carboxylic acid 4,b 5s] and the carbonic acid anhydrides were developed and remain useful despite the... 

Kricheldorf, H., a-Aminoacid-N-Carboxy-anhydrides and Related Heterocycles - Synthesis Properties, Peptide Synthesis, Polymerization, Springer Berlin, (1987) p 3. Leuchs, H. Geiger, W., Ber. Dtsch. Chem. Ges, (1908) 41, 1721. 

Thus, phosgene has proven to be very effective in the preparation of N-carboxy anhydrides (NCA) from a-amino acids. These compounds 2,5-dioxo-1,3-oxazolidines (V), also called Leuch s anhydrides have widespread applications especially but not only In peptides synthesis [Scheme 194]. 

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